JPH11209280A - Anti-influenza drug containing neuraminic acid derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an anti-influenza drug that has excellent sialidase inhibitory action and virus replication inhibitory action and is useful for prevention and treatment of viral infections such as influenza by admixing a specific neuraminic acid derivative as an active ingredient. SOLUTION: This anti-influenza drug contains, as an active ingredient, a compound represented by formula I (R<1> is a 1-4C alkyl; R<2> and R<3> are each H or the like; X is a halogen or the like; Y is NH2 ; Z is oxygen), its pharmacologically acceptable salts or its carboxylic esters; typically 5- acetamide-4-guanidino-2,3,4,5,7-pentadeoxy-7-fluoro-D-glycero-D-galact o-non-2- enopyranosonic acid. The compound of the formula I is prepared, for example, by reaction of a compound of formula II (R<2a> is R<2> or the like; R<3a> is R<3> or the like; W<a> is H or the like; X<a> is X or the like) with N,N'-di-t-butoxycarbonyl thiourea followed by deprotection.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a sialidase inhibitor containing a novel 2-deoxy-2,3-didehydro-N-acylneuraminic acid derivative as an active ingredient, a virus (particularly influenza virus) replication inhibitor, a medicament, The present invention relates to a prophylactic and therapeutic agent for a viral infection (particularly influenza).

[0002]

BACKGROUND OF THE INVENTION Viral infections, such as influenza, are diseases caused by viral infection.
One of the processes in which this virus multiplies is a process in which the offspring virus budding on the cell surface is detached from the cell. The offspring virus, via hemagglutinin on the surface of the offspring virus,
It binds to sialic acid on the cell surface. When the sialidase on the surface of the child virus decomposes the sialic acid, the child virus is detached from the cell and secondary infected to the surrounding cells. Therefore, by inhibiting sialidase, it is possible to prevent detachment of the offspring virus from the cell surface and prevent secondary infection. Therefore, a substance having a sialidase inhibitory action is considered to be effective for treating or preventing a viral infection such as influenza.

On the other hand, it has sialidase inhibitory activity,
As a substance having a deoxy-2,3-didehydro-N-acylneuraminic acid skeleton, a substance described in WO 91/16320 (Japanese Translation of PCT Application No. 5-507068) is known.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies over many years on the synthesis of derivatives having better sialidase inhibitory activity than known substances and their pharmacological activities. It has been found that 2-deoxy-2,3-dihydro-N-acylneuraminic acid derivatives have excellent sialidase inhibitory activity and virus replication inhibitory activity. Furthermore, they have found that when administered to an animal infected with an influenza virus, they show excellent infection prevention and treatment effects, and are therefore useful as anti-influenza drugs, and completed the present invention.

[0005]

The active ingredient of the present invention, 2-deoxy-2,3-dihydro-N-acylneuraminic acid derivative, is represented by the general formula:

[0006]

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[0007] [wherein, R ¹ represents a substituted optionally alkyl group optionally having 1 to 4 carbon in halogen atom, R ²
And R ³ are the same or different and each represent a hydrogen atom or an aliphatic acyl group having 2 to 25 carbon atoms; X represents a hydroxyl group, a halogen atom, an R ^a O— group ( ^Ra represents an aliphatic group having 2 to 25 carbon atoms); An acyl group) or an alkoxy group having 1 to 4 carbon atoms, Y is NH ₂ or R ^b R ^c N—O— group (R ^b and R ^c are the same or different and each represents a hydrogen atom or a carbon atom having 1 to 4 carbon atoms; And Z represents an oxygen atom or a sulfur atom. However, when Y is an NH ₂ group, even if X is a hydroxyl group or a R ^a O— group (R ^a has the same meaning as described above), and R ¹ is substituted with a halogen atom, Compounds which are good alkyl groups having 1 to 4 carbon atoms and Z is an oxygen atom are excluded. A pharmaceutically acceptable salt thereof and a carboxylic acid ester thereof.

The present invention is a pharmaceutical composition containing a compound represented by the above formula (1), a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient.

Further, the present invention relates to a medicament containing a compound represented by the above formula (1), a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient (particularly, a prophylactic and therapeutic agent for influenza). It is.

Further, the present invention is a sialidase inhibitor comprising a compound represented by the above formula (1), a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient.

Furthermore, the present invention relates to a virus (particularly influenza virus) replication inhibitor comprising a compound represented by the above formula (1), a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. is there.

In the above formula (1), as the “alkyl group having 1 to 4 carbon atoms” of the “alkyl group having 1 to 4 carbon atoms which may be substituted by a halogen atom” for R ¹ ,
Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl and tert-butyl groups, preferably a methyl group, and a carbon atom which may be substituted by a halogen atom of R ¹ Examples of the “halogen atom” of the “number 1 to 4 alkyl groups” include fluorine, chlorine, and bromine atoms, preferably a fluorine atom, and the “carbon number that may be substituted with a halogen atom” for R ^1. Examples of the “alkyl group having 1 to 4 carbon atoms substituted with a halogen atom” in the “1 to 4 alkyl groups” include monofluoromethyl,
Difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 1-fluoropropyl,
2-fluoropropyl, 3-fluoropropyl, 4-fluorobutyl, monochloromethyl, 1-chloroethyl,
2-chloroethyl, 1-chloropropyl, 2-chloropropyl, 3-chloropropyl, monobromomethyl, 1-
Bromoethyl, 2-bromoethyl, 1-bromopropyl, 2-bromopropyl, 3-bromopropyl and the like, and preferably a methyl group substituted by a fluorine atom (particularly, a monofluoromethyl and difluoromethyl group) , R ¹ "an alkyl group having 1 to 4 carbon atoms which may be substituted by a halogen atom", that is, R ¹ is preferably a methyl group which may be substituted by a fluorine atom. (Especially methyl, monofluoromethyl and difluoromethyl groups), more preferably a methyl group, and a “C2 to C25 aliphatic acyl group” for R ² and R ³ and R ^{a for} X the of O- group R ^a "aliphatic acyl group having 2 to 25 carbon atoms", for example, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, Valeryl, isovaleryl, octanoyl, nonylcarbonyl, decylcarbonyl, 3-
Methylnonylcarbonyl, 8-methylnonylcarbonyl, 3-ethyloctylcarbonyl, 3,7-dimethyloctylcarbonyl, undecylcarbonyl, dodecylcarbonyl, tridecylcarbonyl, tetradecylcarbonyl, pentadecylcarbonyl, hexadecylcarbonyl, 1-methyl Pentadecylcarbonyl, 14-methylpentadecylcarbonyl, 13,13-dimethyltetradecylcarbonyl, heptadecylcarbonyl, 15-
Examples thereof include alkylcarbonyl groups such as methylhexadecylcarbonyl, octadecylcarbonyl, 1-methylheptadecylcarbonyl, nonadecylcarbonyl, eicosylcarbonyl, and tricosylcarbonyl, and preferably have 6 to 25 carbon atoms. And more preferably those having 8 to 16 carbon atoms (especially octanoyl,
Nonylcarbonyl (i.e., decanoyl), undecylcarbonyl (i.e., dodecanoyl), tridecyl carbonyl (i.e., myristoyl), a pentadecyl carbonyl (i.e., palmitoyl)), R ²
As a whole, preferred are a hydrogen atom or an aliphatic acyl group having 6 to 25 carbon atoms, and more preferred are those having 8 to 16 carbon atoms (particularly, octanoyl, nonylcarbonyl (ie, decanoyl) ), undecylcarbonyl (i.e., dodecanoyl), tridecyl carbonyl (i.e., myristoyl), pentadecyl carbonyl (i.e., palmitoyl)), the entire R ^3, as a suitable, having 6 to hydrogen or C 2
5 aliphatic acyl groups, more preferably those having a hydrogen atom or 8 to 16 carbon atoms (especially octanoyl, nonylcarbonyl (ie, decanoyl), undecylcarbonyl (ie, dodecanoyl), tridecyl Carbonyl (ie, myristoyl), pentadecylcarbonyl (ie, palmitoyl)),
A preferred combination of R ² and R ³ is R ²
Is an aliphatic acyl group having 8 to 16 carbon atoms (particularly, octanoyl, nonylcarbonyl (ie, decanoyl),
Undecylcarbonyl (ie, dodecanoyl), tridecylcarbonyl (ie, myristoyl), pentadecylcarbonyl (ie, palmitoyl), and wherein R ³ is a hydrogen atom; Is a fluorine, chlorine or bromine atom, and is preferably a fluorine atom, and examples of the "alkoxy group having 1 to 4 carbon atoms" for X include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, Examples include s-butoxy and t-butoxy groups, preferably methoxy and ethoxy groups, and as a whole X, preferred are a fluorine atom, methoxy and ethoxy group, and R ^b R ^c N of Y as "an alkyl group having 1 to 4 carbon atoms" is a R ^b and R ^c -O- groups, methyl, ethyl, n- propyl, i Propyl, n- butyl, isobutyl, s- butyl, tert- butyl group, and preferably a methyl group, as a whole R ^b R ^c N-O- group in Y, preferred are, NH ₂ —O— group, and in all of Y,
Preferable is an NH ₂ group or an NH ₂ —O— group, more preferably, an NH ₂ group, and, in Z as a whole, an oxygen atom is preferable.

The compound (1), which is an active ingredient of the present invention, comprises
When it has a carboxy group, it can be a salt,
Salts of “the pharmacologically acceptable salts” include sodium salts, potassium salts, alkali metal salts such as lithium salts,
Metal salts such as alkaline earth metal salts such as calcium salts and magnesium salts, aluminum salts, iron salts, zinc salts, copper salts, nickel salts, and cobalt salts; inorganic salts such as ammonium salts, t-octylamine salts; Dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N′-dibenzylethylenediamine salt, Amine salts such as chloroprocaine salts, procaine salts, diethanolamine salts, N-benzyl-phenethylamine salts, piperazine salts, tetramethylammonium salts, and organic salts such as tris (hydroxymethyl) aminomethane salt;
Even when the compound (1), which is an active ingredient of the present invention, has a guanidino group, it can be converted into a salt. Examples of the “pharmacologically acceptable salt” include hydrofluoric acid and hydrochloride. ,
Inorganic acid salts such as hydrohalides such as hydrobromide and hydroiodide, nitrates, perchlorates, sulfates and phosphates; methanesulfonate, trifluoromethanesulfonate and ethane Lower alkane sulfonates such as sulfonates, benzene sulfonates, aryl sulfonates such as p-toluene sulfonate, acetic acid, trifluoroacetate, malic acid, fumarate, succinic acid Organic acid salts such as salts, citrates, tartrates, oxalates and maleates;
And amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate and aspartate, and preferably sodium salts, potassium salts, alkali metal salts such as lithium salts, and acetates.
Organic acid salts such as trifluoroacetate and inorganic acid salts such as hydrochloride and sulfate can be mentioned.

Examples of the group forming the ester group of “the carboxylic acid ester” include, for example, methyl, ethyl, n-
Propyl, isopropyl, n-butyl, isobutyl, s
-Butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutylheptyl, 1- Methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-propylbutyl, 4,4-dimethylpentyl, octyl, 1-methylheptyl, 2-methylheptyl, 3-methyl Heptyl,
4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1-propylpentyl, 2-ethylhexyl, 5,5-dimethylhexyl, nonyl, 3-methyloctyl, 4-methyloctyl, 5-methyloctyl, 6
-Methyloctyl, 1-propylhexyl, 2-ethylheptyl, 6,6-dimethylheptyl, decyl, 1-methylnonyl, 3-methylnonyl, 8-methylnonyl,
-Ethyloctyl, 3,7-dimethyloctyl, 7,7
-Dimethyloctyl, undecyl, 4,8-dimethylnonyl, dodecyl, tridecyl, tetradecyl, pentadecyl, 3,7,11-trimethyldodecyl, hexadecyl, 4,8,12-trimethyltridecyl, 1-methylpentadecyl, 14- Methylpentadecyl, 13, 13
"Alkyl groups" such as dimethyltetradecyl, heptadecyl, 15-methylhexadecyl, octadecyl, 1-methylheptadecyl, nonadecyl, eicosyl, 3,7,11,15-tetramethylhexadecyl, henicosyl and docosyl groups; Ethenyl, 1-propenyl,
2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl,
2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-
Butenyl, 1-methyl-1-butenyl, 3-methyl-2
-Butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl,
-Pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3
-Pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4
-Pentenyl, 1-hexenyl, 2-hexenyl, 3-
“Alkenyl groups” such as hexenyl, 4-hexenyl, 5-hexenyl; ethynyl, 2-propynyl, 1-methyl-2-propynyl, 2-methyl-2-propynyl,
2-ethyl-2-propynyl, 2-butynyl, 1-methyl-2-butynyl, 2-methyl-2-butynyl, 1-ethyl-2-butynyl, 3-butynyl, 1-methyl-3-
Butynyl, 2-methyl-3-butynyl, 1-ethyl-3
-Butynyl, 2-pentynyl, 1-methyl-2-pentynyl, 2-methyl-2-pentynyl, 3-pentynyl,
1-methyl-3-pentynyl, 2-methyl-3-pentynyl, 4-pentynyl, 1-methyl-4-pentynyl,
"Alkynyl groups" such as 2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl; trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl,
"Halogeno lower alkyl group" such as 6-iodohexyl, 2,2-dibromoethyl; 2-hydroxyethyl,
Hydroxy "lower alkyl group" such as 2,3-dihydroxypropyl, 3-hydroxypropyl, 3,4-dihydroxybutyl, 4-hydroxybutyl; "aliphatic acyl" such as acetylmethyl- "lower alkyl group";
Benzyl, phenethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, 6-phenylhexyl, α-
"Lower alkyl group" substituted with 1 to 3 aryl groups such as naphthyldiphenylmethyl, 9-anthrylmethyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5 -Trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzyldiphenylmethyl, bis ( 2-
Nitrophenyl) substituted with 1 to 3 aryl groups in which the aryl ring is substituted with lower alkyl, lower alkoxy, nitro, halogen, cyano, alkoxycarbonyl groups such as methyl, piperonyl and 4-methoxycarbonylbenzyl. "Aralkyl group" such as a lower alkyl group; trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, tert-butyldimethylsilyl, methyldiisopropylsilyl, methylditert-butylsilyl, triisopropylsilyl, methyldiphenylsilyl, isopropyldiphenylsilyl, butyldiphenyl "Silyl group" such as silyl and phenyldiisopropylsilyl; "protecting group which can be cleaved in vivo by a biological method such as hydrolysis", that is, free acid or its free acid which is hydrolyzed in the human body and the like. Salt Esters formed, specifically, methoxymethyl, 1-ethoxyethyl, 1-methyl-1-
Methoxyethyl, 1- (isopropoxy) ethyl, 2-
Lower alkoxy lower alkyl groups such as methoxyethyl, 2-ethoxyethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, n-propoxymethyl, isopropoxymethyl, n-butoxymethyl and tert-butoxymethyl; Lower alkoxylated lower alkoxy lower alkyl groups such as -methoxyethoxymethyl, "aryl" oxy "lower alkyl groups" such as phenoxymethyl, 2,2,2-trichloroethoxymethyl, bis (2-chloroethoxy) methyl "Alkoxy lower alkyl group" such as halogenated lower alkoxy lower alkyl group; "lower alkoxy" carbonyl "lower alkyl group" such as methoxycarbonylmethyl; cyano "lower alkyl group" such as cyanomethyl and 2-cyanoethyl; Methylthiomethyl, d An "aryl" thiomethyl group such as phenylthiomethyl, naphthylthiomethyl; may be substituted with a halogen such as 2-methanesulfonylethyl, 2-trifluoromethanesulfonylethyl; "Lower alkyl" sulfonyl "lower alkyl group";"aryl" sulfonyl "lower alkyl group" such as 2-benzenesulfonylethyl and 2-toluenesulfonylethyl; formyloxymethyl, acetoxymethyl, propionyloxymethyl, butyryloxymethyl , Pivaloyloxymethyl, valeryloxymethyl,
Isovaleryloxymethyl, hexanoyloxymethyl, 1-formyloxyethyl, 1-acetoxyethyl, 1-propionyloxyethyl, 1-butyryloxyethyl, 1-pivaloyloxyethyl, 1-valeryloxyethyl, 1-isovaleryloxyethyl, 1-hexanoyloxyethyl, 2-formyloxyethyl,
2-acetoxyethyl, 2-propionyloxyethyl, 2-butyryloxyethyl, 2-pivaloyloxyethyl, 2-valeryloxyethyl, 2-isovaleryloxyethyl, 2-hexanoyloxyethyl, 1- Formyloxypropyl, 1-acetoxypropyl, 1-
Propionyloxypropyl, 1-butyryloxypropyl, 1-pivaloyloxypropyl, 1-valeryloxypropyl, 1-isovaleryloxypropyl, 1-
Hexanoyloxypropyl, 1-acetoxybutyl,
1-propionyloxybutyl, 1-butyryloxybutyl, 1-pivaloyloxybutyl, 1-acetoxypentyl, 1-propionyloxypentyl, 1-butyryloxypentyl, 1-pivaloyloxypentyl, 1
"Aliphatic acyl" such as pivaloyloxyhexyl
Oxy "lower alkyl group", cyclopentanoyloxymethyl, cyclohexanoyloxymethyl, 1-cyclopentanoyloxyethyl, 1-cyclohexanoyloxyethyl, 1-cyclopentanoyloxypropyl,
"Cycloalkyl" carbonyloxy "lower alkyl" such as 1-cyclohexanoyloxypropyl, 1-cyclopentanoyloxybutyl, 1-cyclohexanoyloxybutyl, "aromatic acyl" oxy such as benzoyloxymethyl Acyloxy "lower alkyl group" such as "lower alkyl group"; methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, propoxycarbonyloxymethyl, isopropoxycarbonyloxymethyl, butoxycarbonyloxymethyl, isobutoxycarbonyloxymethyl, pentyloxycarbonyloxy Methyl, hexyloxycarbonyloxymethyl, cyclohexyloxycarbonyloxymethyl,
Cyclohexyloxycarbonyloxy (cyclohexyl) methyl, 1- (methoxycarbonyloxy) ethyl, 1- (ethoxycarbonyloxy) ethyl, 1-propoxycarbonyloxyethyl, 1- (isopropoxycarbonyloxy) ethyl, 1-butoxycarbonyloxyethyl , 1-isobutoxycarbonyloxyethyl, 1- (tert-butoxycarbonyloxy) ethyl,
1-pentyloxycarbonyloxyethyl, 1-hexyloxycarbonyloxyethyl, 1-cyclopentyloxycarbonyloxyethyl, 1-cyclopentyloxycarbonyloxypropyl, 1-cyclohexyloxycarbonyloxypropyl, 1-cyclopentyloxycarbonyloxybutyl, Cyclohexyloxycarbonyloxybutyl, 1- (cyclohexyloxycarbonyloxy) ethyl, 1- (ethoxycarbonyloxy) propyl, 2-methoxycarbonyloxyethyl, 2-ethoxycarbonyloxyethyl, 2-propoxycarbonyloxyethyl, 2-isopropoxy Carbonyloxyethyl, 2-butoxycarbonyloxyethyl, 2-isobutoxycarbonyloxyethyl,
2-pentyloxycarbonyloxyethyl, 2-hexyloxycarbonyloxyethyl, 1-methoxycarbonyloxypropyl, 1-ethoxycarbonyloxypropyl, 1-propoxycarbonyloxypropyl,
1-isopropoxycarbonyloxypropyl, 1-butoxycarbonyloxypropyl, 1-isobutoxycarbonyloxypropyl, 1-pentyloxycarbonyloxypropyl, 1-hexyloxycarbonyloxypropyl, 1-methoxycarbonyloxybutyl,
-Ethoxycarbonyloxybutyl, 1-propoxycarbonyloxybutyl, 1-isopropoxycarbonyloxybutyl, 1-butoxycarbonyloxybutyl,
(Alkoxycarbonyloxy) alkyl groups such as 1-isobutoxycarbonyloxybutyl, 1-methoxycarbonyloxypentyl, 1-ethoxycarbonyloxypentyl, 1-methoxycarbonyloxyhexyl, 1-ethoxycarbonyloxyhexyl; (5-phenyl -2-oxo-1,3-dioxolen-4-yl) methyl, [5- (4-methylphenyl) -2-oxo-1,3-dioxolen-4-yl] methyl, [5-
(4-methoxyphenyl) -2-oxo-1,3-dioxolen-4-yl] methyl, [5- (4-fluorophenyl) -2-oxo-1,3-dioxolen-4-yl] methyl, [ 5- (4-chlorophenyl) -2-oxo-1,3-dioxolen-4-yl] methyl, (2-
Oxo-1,3-dioxolen-4-yl) methyl,
(5-methyl-2-oxo-1,3-dioxolen-4
-Yl) methyl, (5-ethyl-2-oxo-1,3-
Dioxolen-4-yl) methyl, (5-propyl-2)
-Oxo-1,3-dioxolen-4-yl) methyl,
(5-isopropyl-2-oxo-1,3-dioxolen-4-yl) methyl, (5-butyl-2-oxo-)
"Carbonyloxyalkyl group" such as oxodioxorenylmethyl group such as 1,3-dioxolen-4-yl) methyl: "phthalidyl group" such as phthalidyl, dimethylphthalidyl, dimethoxyphthalidyl: phenyl, indanyl Such as "aryl group": the above "alkyl group": "carboxyalkyl group" such as carboxymethyl; and "amino acid amide-forming residue" such as phenylalanine. A linear or branched alkyl group having 6 to 25 carbon atoms,
More preferably, it has 16 to 25 carbon atoms.

The compound (1), which is an active ingredient of the present invention, comprises:
When left in the air, water may be absorbed, adsorbed water may be attached, or a hydrate may be formed. Such salts are also included in the present invention. Among the compound which is the active ingredient of the present invention, the suitable, 1) R ¹ is, compounds are also good methyl group substituted by a fluorine atom, 2) R ¹ is methyl, monofluoromethyl or 3) a compound in which R ¹ is a methyl group, 4) a compound in which R ² is a hydrogen atom or an aliphatic acyl group having 8 to 16 carbon atoms, 5) a compound in which R ² is octanoyl A compound in which R ³ is a hydrogen atom or an aliphatic acyl group having 8 to 16 carbon atoms; 7) a compound in which R ³ is a hydrogen atom or octanoyl, decanoyl, or a decanoyl, dodecanoyl, myristoyl or palmitoyl group;
A compound which is a dodecanoyl, myristoyl or palmitoyl group; 8) a compound wherein R ² is an aliphatic acyl group having 8 to 16 carbon atoms and R ³ is a hydrogen atom; 9) R ² is octanoyl; A decanoyl, dodecanoyl, myristoyl or palmitoyl group;
A compound wherein ³ is a hydrogen atom; 10) a compound wherein X is a fluorine atom, a methoxy group or an ethoxy group; 11) a compound wherein Y is an NH ₂ or NH ₂ —O— group (aminooxy group); A) compounds wherein Y is an NH ₂ group; and 13) compounds wherein Z is an oxygen atom.

Also, R ¹ is selected from 1) to 3),
² is selected from 4) to 5), R ³ is selected from 6) to 7), X is selected from 10), and Y is 11) to 12).
And compounds obtained by selecting Z from 13) and combining them are also suitable.

The compounds which are the active ingredients of the present invention are illustrated below, but the active ingredients of the present invention are not limited thereto.

Specific compounds contained in the active ingredient of the present invention include the following compounds (1 ') obtained by combining the compounds selected from the combinations of groups shown in Tables 1 and 2. Can be

For example, in Table 1, No. No. 1 and Table 2
The combination of 4 represents the following compound (1 ″). When the compound (1 ″) is specifically shown,
1-4.

In Tables 1 and 2, Me represents a methyl group, Et represents an ethyl group, Pr represents a propyl group, i Pr represents an isopropyl group, Bu represents a butyl group, and i Bu represents an isobutyl group. Show.

[0021]

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[0022]

[Table 1] Ｎｏ No. R ¹ XYZ ──────────────────────────────── 1 CH ₃ F NH ₂ O 2 CF ₂ HF NH ₂ O 3 CFH ₂ F NH ₂ O 4 CH ₃ F NH ₂ S 5 CF ₂ HF NH ₂ S 6 CFH ₂ F NH ₂ S 7 CH ₃ F ONH ₂ O 8 CF ₂ HF ONH ₂ O 9 CFH ₂ F ONH ₂ O 10 CH ₃ F ONH ₂ S 11 CF ₂ HF ONH ₂ S 12 CFH ₂ F ONH ₂ S 13 CH ₃ F ONHMe O 14 CF ₂ HF ONHEt O 15 CFH ₂ F ONHPr O 16 CH ₃ F ONHMe S 17 CF ₂ HF ONHBu S 18 CFH ₂ F ONHMe S 19 CH ₃ F ON (Me) ₂ O 20 CF ₂ HF ON (Et) ₂ O 21 CFH ₂ F ON (Pr) ₂ O 22 CH ₃ F ON (Me) ₂ S 23 CF ₂ HF ON (Bu) ₂ S 24 CFH ₂ F ON (Me) Et S 25 CH ₃ Cl NH ₂ O 26 CF ₂ H Br NH ₂ O 27 CFH ₂ Br NH ₂ O 28 CH ₃ Cl NH ₂ S 29 CF ₂ H Cl NH ₂ S 30 CFH ₂ Br NH ₂ S 31 CH ₃ OH NH ₂ S 32 CF ₂ H OH NH ₂ S 33 CFH ₂ OH NH ₂ S 34 CH ₃ OH ONH ₂ O 35 CF ₂ H OH ONH ₂ O 36 CFH ₂ OH ONH ₂ O 37 CH ₃ OH ONH ₂ S 38 CF ₂ H OH ONH ₂ S 39 CFH ₂ OH ONH ₂ S 40 CH ₃ OH ONHMe O 41 CF ₂ H OH ONHEt O 42 CFH ₂ OH ONHPr O 43 CH ₃ OH ONHMe S 44 CF ₂ H OH ONHBu S 45 CFH ₂ OH ONHMe S 46 CH ₃ OH ON (Me) ₂ O 4 7 CF ₂ H OH ON (Et) ₂ O 48 CFH ₂ OH ON (Pr) ₂ O 49 CH ₃ OH ON (Me) ₂ S 50 CF ₂ H OH ON (Bu) ₂ S 51 CFH ₂ OH ON (Me) Et S 52 Et F NH ₂ O 53 CF ₃ CH ₂ F NH ₂ O 54 Pr F NH ₂ O 55 Bu F NH ₂ S 56 i Pr F NH ₂ S 57 i Bu F NH ₂ S 58 Bu OH NH ₂ S 59 i Pr OH NH ₂ S 60 i Bu OH NH ₂ S 61 Et F ONH ₂ O 62 CF ₃ CH ₂ F ONH ₂ O 63 Pr F ONH ₂ O 64 Bu F ONH ₂ S 65 i Pr F ONH ₂ S 66 i Bu F ONH ₂ S 67 Et CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 68 CF ₃ CH ₂ CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 69 Pr CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 70 Bu CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 71 i Pr CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 72 i Bu CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 73 CH ₃ CH ₃ (CH ₂ ) ₄ COO NH ₂ S 74 CF ₂ H CH ₃ (CH ₂ ) ₄ COO NH ₂ S 75 CFH ₂ CH ₃ (CH ₂ ) ₄ COO NH ₂ S 76 CH ₃ CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 77 CF ₂ H CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 78 CFH ₂ CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 79 CH ₃ CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 80 CF ₂ H CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 81 CFH ₂ CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 82 CH ₃ CH ₃ (CH ₂ ) ₄ COO ONHMe O 83 CF ₂ H CH ₃ (CH ₂ ) ₄ COO ONHEt O 84 CFH ₂ CH ₃ (CH ₂ ) ₄ COO ONHPr O 85 CH ₃ CH ₃ (CH ₂ ) ₄ COO ONHMe S 86 CF ₂ H CH ₃ (CH ₂ ) ₄ COO ONHBu S 87 CFH ₂ CH ₃ (CH ₂ ) ₄ COO ONHMe S 88 CH ₃ CH ₃ (CH ₂ ) ₄ COO ON (Me) ₂ O 89 CF ₂ H CH ₃ (CH ₂ ) ₄ COO ON (Et) ₂ O 90 CFH ₂ CH ₃ (CH ₂ ) ₄ COO ON (Pr) ₂ O 91 CH ₃ CH ₃ (CH ₂ ) ₄ COO ON (Me) ₂ S 92 CF ₂ H CH ₃ (CH ₂ ) ₄ COO ON (Bu) ₂ S 93 CFH ₂ CH ₃ (CH ₂ ) ₄ COO ON (Me) Et S 94 Bu CH ₃ (CH ₂ ) ₄ COO NH ₂ S 95 i Pr CH ₃ (CH ₂ ) ₄ COO NH ₂ S 96 i Bu CH ₃ (CH ₂ ) ₄ COO NH ₂ S 97 Et CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 98 CF ₃ CH ₂ CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 99 Pr CH ₃ (CH ₂ ) ₄ COO ONH ₂ O 100 Bu CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 101 i Pr CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 102 i Bu CH ₃ (CH ₂ ) ₄ COO ONH ₂ S 103 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO NH ₂ S 104 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO NH ₂ S 105 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO NH ₂ S 106 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ O 107 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ O 108 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ O 109 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ S 110 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ S 111 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO ON H ₂ S 112 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO ONHMe O 113 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO ONHEt O 114 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO ONHPr O 115 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO ONHMe S 116 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO ONHBu S 117 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO ONHMe S 118 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO ON (Me) ₂ O 119 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO ON (Et) ₂ O 120 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO ON (Pr) ₂ O 121 CH ₃ CH ₃ (CH ₂ ) ₁₂ COO ON (Me) ₂ S 122 CF ₂ H CH ₃ (CH ₂ ) ₁₂ COO ON (Bu) ₂ S 123 CFH ₂ CH ₃ (CH ₂ ) ₁₂ COO ON (Me) Et S 124 Bu CH ₃ (CH ₂ ) ₁₂ COO NH ₂ S 125 i Pr CH ₃ (CH ₂ ) ₁₂ COO NH ₂ S 126 i Bu CH ₃ (CH ₂ ) ₁₂ COO NH ₂ S 127 Et CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ O 128 CF ₃ CH ₂ CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ O 129 Pr CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ O 130 Bu CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ S 131 i Pr CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ S 132 i Bu CH ₃ (CH ₂ ) ₁₂ COO ONH ₂ S 133 CH ₃ CH ₃ (CH ₂ ) ₂ COO NH ₂ S 134 CF ₂ H CH ₃ (CH ₂ ) ₃ COO NH ₂ S 135 CFH ₂ CH ₃ (CH ₂ ) ₅ COO NH ₂ S 136 CH ₃ CH ₃ (CH ₂ ) ₆ COO ONH ₂ O 137 CF ₂ H CH ₃ (CH ₂ ) ₈ COO ONH ₂ O 138 CFH ₂ C H ₃ (CH ₂ ) ₁₀ COO ONH ₂ O 139 CH ₃ CH ₃ (CH ₂ ) ₁₄ COO ONH ₂ S 140 CF ₂ H CH ₃ (CH ₂ ) ₁₆ COO ONH ₂ S 141 CFH ₂ CH ₃ (CH ₂ ) ₁₈ COO ONH ₂ S 142 CH ₃ CH ₃ (CH ₂ ) ₂₀ COO ONHMe O 143 CF ₂ H CH ₃ (CH ₂ ) ₂₂ COO ONHEt O 144 CFH ₂ CH ₃ CH ₂ COO ONHPr O 145 CH ₃ CH ₃ (CH ₂ ) ₂ COO ONHMe S 146 CF ₂ H CH ₃ (CH ₂ ) ₃ COO ONHBu S 147 CFH ₂ CH ₃ (CH ₂ ) ₅ COO ONHMe S 148 CH ₃ CH ₃ (CH ₂ ) ₆ COO ON (Me) ₂ O 149 CF ₂ H CH ₃ (CH ₂ ) ₈ COO ON (Et) ₂ O 150 CFH ₂ CH ₃ (CH ₂ ) ₁₀ COO ON (Pr) ₂ O 151 CH ₃ CH ₃ (CH ₂ ) ₁₄ COO ON (Me) ₂ S 152 CF ₂ H CH ₃ (CH ₂ ) ₁₆ COO ON (Bu) ₂ S 153 CFH ₂ CH ₃ (CH ₂ ) ₁₈ COO ON (Me) Et S 154 Bu CH ₃ (CH ₂ ) ₂ COO NH ₂ S 155 i Pr CH ₃ (CH ₂ ) ₃ COO NH ₂ S 156 i Bu CH ₃ (CH ₂ ) ₅ COO NH ₂ S 157 Et CH ₃ (CH ₂ ) ₆ COO ONH ₂ O 158 CF ₃ CH ₂ CH ₃ (CH ₂ ) ₈ COO ONH ₂ O 159 Pr CH ₃ (CH ₂ ) ₁₀ COO ONH ₂ O 160 Bu CH ₃ (CH ₂ ) ₁₄ COO ONH ₂ S 161 i Pr CH ₃ (CH ₂ ) ₁₆ COO ONH ₂ S 162 i Bu CH ₃ (CH ₂ ) ₁₈ COO ONH ₂ S 163 CH ₃ OMe NH ₂ O 164 CF ₂ H OMe NH ₂ O 165 CFH ₂ OMe NH ₂ O 166 CH ₃ OM e NH ₂ S 167 CF ₂ H OMe NH ₂ S 168 CFH ₂ OMe NH ₂ S 169 CH ₃ OMe ONH ₂ O 170 CF ₂ H OMe ONH ₂ O 171 CFH ₂ OMe ONH ₂ O 172 CH ₃ OMe ONH ₂ S 173 CF ₂ H OMe ONH ₂ S 174 CFH ₂ OMe ONH ₂ S 175 CH ₃ OMe ONHMe O 176 CF ₂ H OMe ONHEt O 177 CFH ₂ OMe ONHPr O 178 CH ₃ OMe ONHMe S 179 CF ₂ H OMe ONHBu S 180 CFH ₂ OMe ONHMe S 181 CH ₃ OMe ON (Me) ₂ O 182 CF ₂ H OMe ON (Et) ₂ O 183 CFH ₂ OMe ON (Pr) ₂ O 184 CH ₃ OMe ON (Me) ₂ S 185 CF ₂ H OMe ON (Bu ) ₂ S 186 CFH ₂ OMe ON (Me) Et S 187 Et OMe NH ₂ O 188 CF ₃ CH ₂ OMe NH ₂ O 189 Pr OMe NH ₂ O 190 Bu OMe NH ₂ S 191 i Pr OMe NH ₂ S 192 i Bu OMe NH ₂ S 193 Et OMe ONH ₂ O 194 CF ₃ CH ₂ OMe ONH ₂ O 195 Pr OMe ONH ₂ O 196 Bu OMe ONH ₂ S 197 i Pr OMe ONH ₂ S 198 i Bu OMe ONH ₂ S 199 CH ₃ OEt NH ₂ O 200 CF ₂ H OEt NH ₂ O 201 CFH ₂ OEt NH ₂ O 202 CH ₃ OEt NH ₂ S 203 CF ₂ H OEt NH ₂ S 204 CFH ₂ OEt NH ₂ S 205 CH ₃ OEt ONH ₂ O 206 CF ₂ H OEt ONH ₂ O 207 CFH ₂ OEt ONH ₂ O 208 CH ₃ OEt ONH ₂ S 209 CF ₂ H OEt ONH ₂ S 210 CFH ₂ OEt ONH ₂ S 211 CH ₃ OEt ONHMe O 212 CF ₂ H OEt ONHEt O 213 CFH ₂ OEt ONHPr O 214 CH ₃ OEt ONHMe S 215 CF ₂ H OEt ONHBu S 216 CFH ₂ OEt ONHMe S 217 CH ₃ OEt ON (Me) ₂ O 218 CF ₂ H OEt ON (Et) ₂ O 219 CFH ₂ OEt ON (Pr) ₂ O 220 CH ₃ OEt ON (Me) ₂ S 221 CF ₂ H OEt ON (Bu) ₂ S 222 CFH ₂ OEt ON (Me) Et S 223 Et OEt NH ₂ O 224 CF ₃ CH ₂ OEt NH ₂ O 225 Pr OEt NH ₂ O 226 Bu OEt NH ₂ S 227 i Pr OEt NH ₂ S 228 i Bu OEt NH ₂ S 229 Et OEt ONH ₂ O 230 CF ₃ CH ₂ OEt ONH ₂ O 231 Pr OEt ONH ₂ O 232 Bu OEt ONH ₂ S 233 i Pr OEt ONH ₂ S 234 i Bu OEt ONH ₂ S ──────────────────────────── ────

[0023]

[Table 2] Ｎｏ No. R ^Two R ^Three W ──────────────────────────────── 1 HHH 2 HH CH _Three 3 HH (CH _Two ) _Five CH _Three 4 HH (CH _Two ) _Ten CH _Three 5 HH (CH _Two ) ₁₃ CH _Three 6 HH (CH _Two ) _Fifteen CH _Three 7 HH (CH _Two ) ₁₇ CH _Three 8 HH (CH _Two ) _{twenty one} CH _Three 9 H CH _Three CO H 10 H CH _Three CH _Two CO H 11 H CH _Three (CH _Two ) _Two CO H 12 H CH _Three (CH _Two ) _Three CO H 13 H CH _Three (CH _Two ) _Four CO H 14 H CH _Three (CH _Two ) _Five CO H 15 H CH _Three (CH _Two ) ₆ CO H 16 H CH _Three (CH _Two ) ₈ CO H 17 H CH _Three (CH _Two ) _Ten CO H 18 H CH _Three (CH _Two ) ₁₂ CO H 19 H CH _Three (CH _Two ) ₁₄ CO H 20 H CH _Three (CH _Two ) ₁₆ CO H 21 H CH _Three (CH _Two ) ₁₈ CO H 22 H CH _Three (CH _Two ) ₂₀ CO H 23 H CH _Three (CH _Two ) _{twenty two} CO H 24 H CH _Three (CH _Two ) _Four CO CH _Three 25 H CH _Three (CH _Two ) _Four CO (CH _Two ) _Five CH _Three 26 H CH _Three (CH _Two ) _Four CO (CH _Two ) _Ten CH _Three 27 H CH _Three (CH _Two ) _Four CO (CH _Two ) ₁₃ CH _Three 28 H CH _Three (CH _Two ) ₁₂ CO CH _Three 29 H CH _Three (CH _Two ) ₁₂ CO (CH _Two ) _Five CH _Three 30 H CH _Three (CH _Two ) ₁₂ CO (CH _Two ) _Ten CH _Three 31 H CH _Three (CH _Two ) ₁₂ CO (CH _Two ) ₁₃ CH _Three 32 CH _Three CO HH 33 CH _Three CH _Two CO HH 34 CH _Three (CH _Two ) _Two CO HH 35 CH _Three (CH _Two ) _Three CO HH 36 CH _Three (CH _Two ) _Four CO HH 37 CH _Three (CH _Two ) _Five CO HH 38 CH _Three (CH _Two ) ₆ CO HH 39 CH _Three (CH _Two ) ₈ CO HH 40 CH _Three (CH _Two ) _Ten CO HH 41 CH _Three (CH _Two ) ₁₂ CO HH 42 CH _Three (CH _Two ) ₁₄ CO HH 43 CH _Three (CH _Two ) ₁₆ CO HH 44 CH _Three (CH _Two ) ₁₈ CO HH 45 CH _Three (CH _Two ) ₂₀ CO HH 46 CH _Three (CH _Two ) _Four CO H CH _Three 47 CH _Three (CH _Two ) _Four CO H (CH _Two ) _Five CH _Three 48 CH _Three (CH _Two ) _Four CO H (CH _Two ) _Ten CH _Three 49 CH _Three (CH _Two ) _Four CO H (CH _Two ) ₁₃ CH _Three 50 CH _Three (CH _Two ) ₁₂ CO H CH _Three 51 CH _Three (CH _Two ) ₁₂ CO H (CH _Two ) _Five CH _Three 52 CH _Three (CH _Two ) ₁₂ CO H (CH _Two ) _Ten CH _Three 53 CH _Three (CH _Two ) ₁₂ CO H (CH _Two ) ₁₃ CH _Three 54 CH _Three CO CH _Three CO H 55 CH _Three CH _Two CO CH _Three CH _Two CO H 56 CH _Three (CH _Two ) _Two CO CH _Three (CH _Two ) _Two CO H 57 CH _Three (CH _Two ) _Three CO CH _Three (CH _Two ) _Three CO H 58 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) _Four CO H 59 CH _Three (CH _Two ) _Five CO CH _Three (CH _Two ) _Five CO H 60 CH _Three (CH _Two ) ₆ CO CH _Three (CH _Two ) ₆ CO H 61 CH _Three (CH _Two ) ₈ CO CH _Three (CH _Two ) ₈ CO H 62 CH _Three (CH _Two ) _Ten CO CH _Three (CH _Two ) _Ten CO H 63 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) ₁₂ CO H 64 CH _Three (CH _Two ) ₁₄ CO CH _Three (CH _Two ) ₁₄ CO H 65 CH _Three (CH _Two ) ₁₆ CO CH _Three (CH _Two ) ₁₆ CO H 66 CH _Three (CH _Two ) ₁₈ CO CH _Three (CH _Two ) ₁₈ CO H 67 CH _Three (CH _Two ) ₂₀ CO CH _Three (CH _Two ) ₂₀ CO H 68 CH _Three (CH _Two ) _{twenty two} CO CH _Three (CH _Two ) _{twenty two} CO H 69 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) ₆ CO H 70 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) ₁₂ CO H 71 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) _Four CO CH _Three 72 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) _Four CO (CH _Two ) _Five CH _Three 73 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) _Four CO (CH _Two ) _Ten CH _Three 74 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) _Four CO (CH _Two ) ₁₃ CH _Three 75 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) ₁₂ CO CH _Three 76 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) ₁₂ CO (CH _Two ) _Five CH _Three 77 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) ₁₂ CO (CH _Two ) _Ten CH _Three 78 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) ₁₂ CO (CH _Two ) ₁₃ CH _Three 79 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) ₁₂ CO CH _Three 80 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) ₁₂ CO (CH _Two ) _Five CH _Three 81 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) ₁₂ CO (CH _Two ) _Ten CH _Three 82 CH _Three (CH _Two ) _Four CO CH _Three (CH _Two ) ₁₂ CO (CH _Two ) ₁₃ CH _Three 83 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) _Four CO CH _Three 84 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) _Four CO (CH _Two ) _Five CH _Three 85 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) _Four CO (CH _Two ) _Ten CH _Three 86 CH _Three (CH _Two ) ₁₂ CO CH _Three (CH _Two ) _Four CO (CH _Two ) ₁₃ CH _Three 87 CH _Three (CH _Two ) ₆ CO H CH _Three 88 CH _Three (CH _Two ) ₈ CO H CH _Three 89 CH _Three (CH _Two ) _Ten CO H CH _Three 90 CH _Three (CH _Two ) ₁₄ CO H CH _Three 91 CH _Three (CH _Two ) ₁₆ CO H CH _Three 92 CH _Three (CH _Two ) ₆ CO H CH _Two CH _Three 93 CH _Three (CH _Two ) ₈ CO H CH _Two CH _Three 94 CH _Three (CH _Two ) _Ten CO H CH _Two CH _Three 95 CH _Three (CH _Two ) ₁₂ CO H CH _Two CH _Three 96 CH _Three (CH _Two ) ₁₄ CO H CH _Two CH _Three 97 CH _Three (CH _Two ) ₁₆ CO H CH _Two CH _Three ──────────────────────────────── Specific examples of compounds include No. 1-1, 1-2, 1-3, 1-
4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-1
3, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21,
1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1
-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-3
8, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46,
1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1
-55, 1-56, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-6
3, 1-64, 1-65, 1-66, 1-67, 1-68, 1-69, 1-70, 1-71,
1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1
-80, 1-81, 1-82, 1-83, 1-84, 1-85, 1-86, 1-87, 1-8
8, 1-89, 1-90, 1-91, 1-92, 1-93, 1-94, 1-95, 1-96,
1-97,2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9,
2-10, 2-11, 2-12, 2-13, 2-14, 2-15, 2-16, 2-17, 2
-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 2-25, 2-2
6, 2-27, 2-28, 2-29, 2-30, 2-31, 2-32, 2-33, 2-34,
2-35, 2-36, 2-37, 2-38, 2-39, 2-40, 2-41, 2-42, 2
-43, 2-44, 2-45, 2-46, 2-47, 2-48, 2-49, 2-50, 2-5
1, 2-52, 2-53, 2-54, 2-55, 2-56, 2-57, 2-58, 2-59,
2-60, 2-61, 2-62, 2-63, 2-64, 2-65, 2-66, 2-67, 2
-68, 2-69, 2-70, 2-71, 2-72, 2-73, 2-74, 2-75, 2-7
6, 2-77, 2-78, 2-79, 2-80, 2-81, 2-82, 2-83, 2-84,
2-85, 2-86, 2-87, 2-88, 2-89, 2-90, 2-91, 2-92, 2
-93, 2-94, 2-95, 2-96, 2-97,3-1, 3-2, 3-3, 3-4, 3-
5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, 3-12, 3-13, 3-1
4, 3-15, 3-16, 3-17, 3-18, 3-19, 3-20, 3-21, 3-22,
3-23, 3-24, 3-25, 3-26, 3-27, 3-28, 3-29, 3-30, 3
-31, 3-32, 3-33, 3-34, 3-35, 3-36, 3-37, 3-38, 3-3
9, 3-40, 3-41, 3-42, 3-43, 3-44, 3-45, 3-46, 3-47,
3-48, 3-49, 3-50, 3-51, 3-52, 3-53, 3-54, 3-55, 3
-56, 3-57, 3-58, 3-59, 3-60, 3-61, 3-62, 3-63, 3-6
4, 3-65, 3-66, 3-67, 3-68, 3-69, 3-70, 3-71, 3-72,
3-73, 3-74, 3-75, 3-76, 3-77, 3-78, 3-79, 3-80, 3
-81, 3-82, 3-83, 3-84, 3-85, 3-86, 3-87, 3-88, 3-8
9, 3-90, 3-91, 3-92, 3-93, 3-94, 3-95, 3-96, 3-97,
4-1, 4-2, 4-3, 4-4, 4-5, 4-6, 4-7, 4-8, 4-9, 4-10,
4-11, 4-12, 4-13, 4-14, 4-15, 4-16, 4-17, 4-18, 4
-19, 4-20, 4-21, 4-22, 4-23, 4-24, 4-25, 4-26, 4-2
7, 4-28, 4-29, 4-30, 4-31, 4-32, 4-33, 4-34, 4-35,
4-36, 4-37, 4-38, 4-39, 4-40, 4-41, 4-42, 4-43, 4
-44, 4-45, 4-46, 4-47, 4-48, 4-49, 4-50, 4-51, 4-5
2, 4-53, 4-54, 4-55, 4-56, 4-57, 4-58, 4-59, 4-60,
4-61, 4-62, 4-63, 4-64, 4-65, 4-66, 4-67, 4-68, 4
-69, 4-70, 4-71, 4-72, 4-73, 4-74, 4-75, 4-76, 4-7
7, 4-78, 4-79, 4-80, 4-81, 4-82, 4-83, 4-84, 4-85,
4-86, 4-87, 4-88, 4-89, 4-90, 4-91, 4-92, 4-93, 4
-94, 4-95, 4-96, 4-97,5-1, 5-2, 5-3, 5-4, 5-5, 5-
6, 5-7, 5-8, 5-9, 5-10, 5-11, 5-12, 5-13, 5-14, 5-
15, 5-16, 5-17, 5-18, 5-19, 5-20, 5-21, 5-22, 5-2
3, 5-24, 5-25, 5-26, 5-27, 5-28, 5-29, 5-30, 5-31,
5-32, 5-33, 5-34, 5-35, 5-36, 5-37, 5-38, 5-39, 5
-40, 5-41, 5-42, 5-43, 5-44, 5-45, 5-46, 5-47, 5-4
8, 5-49, 5-50, 5-51, 5-52, 5-53, 5-54, 5-55, 5-56,
5-57, 5-58, 5-59, 5-60, 5-61, 5-62, 5-63, 5-64, 5
-65, 5-66, 5-67, 5-68, 5-69, 5-70, 5-71, 5-72, 5-7
3, 5-74, 5-75, 5-76, 5-77, 5-78, 5-79, 5-80, 5-81,
5-82, 5-83, 5-84, 5-85, 5-86, 5-87, 5-88, 5-89, 5
-90, 5-91, 5-92, 5-93, 5-94, 5-95, 5-96, 5-97,6-1,
6-2, 6-3, 6-4, 6-5, 6-6, 6-7, 6-8, 6-9, 6-10, 6-1
1, 6-12, 6-13, 6-14, 6-15, 6-16, 6-17, 6-18, 6-19,
6-20, 6-21, 6-22, 6-23, 6-24, 6-25, 6-26, 6-27, 6
-28, 6-29, 6-30, 6-31, 6-32, 6-33, 6-34, 6-35, 6-3
6, 6-37, 6-38, 6-39, 6-40, 6-41, 6-42, 6-43, 6-44,
6-45, 6-46, 6-47, 6-48, 6-49, 6-50, 6-51, 6-52, 6
-53, 6-54, 6-55, 6-56, 6-57, 6-58, 6-59, 6-60, 6-6
1, 6-62, 6-63, 6-64, 6-65, 6-66, 6-67, 6-68, 6-69,
6-70, 6-71, 6-72, 6-73, 6-74, 6-75, 6-76, 6-77, 6
-78, 6-79, 6-80, 6-81, 6-82, 6-83, 6-84, 6-85, 6-8
6, 6-87, 6-88, 6-89, 6-90, 6-91, 6-92, 6-93, 6-94,
6-95, 6-96, 6-97,7-1, 7-2, 7-3, 7-4, 7-5, 7-6, 7-
7, 7-8, 7-9, 7-10, 7-11, 7-12, 7-13, 7-14, 7-15, 7
-16, 7-17, 7-18, 7-19, 7-20, 7-21, 7-22, 7-23, 7-2
4, 7-25, 7-26, 7-27, 7-28, 7-29, 7-30, 7-31, 7-32,
7-33, 7-34, 7-35, 7-36, 7-37, 7-38, 7-39, 7-40, 7
-41, 7-42, 7-43, 7-44, 7-45, 7-46, 7-47, 7-48, 7-4
9, 7-50, 7-51, 7-52, 7-53, 7-54, 7-55, 7-56, 7-57,
7-58, 7-59, 7-60, 7-61, 7-62, 7-63, 7-64, 7-65, 7
-66, 7-67, 7-68, 7-69, 7-70, 7-71, 7-72, 7-73, 7-7
4, 7-75, 7-76, 7-77, 7-78, 7-79, 7-80, 7-81, 7-82,
7-83, 7-84, 7-85, 7-86, 7-87, 7-88, 7-89, 7-90, 7
-91, 7-92, 7-93, 7-94, 7-95, 7-96, 7-97,8-1, 8-2,
8-3, 8-4, 8-5, 8-6, 8-7, 8-8, 8-9, 8-10, 8-11, 8-1
2, 8-13, 8-14, 8-15, 8-16, 8-17, 8-18, 8-19, 8-20,
8-21, 8-22, 8-23, 8-24, 8-25, 8-26, 8-27, 8-28, 8
-29, 8-30, 8-31, 8-32, 8-33, 8-34, 8-35, 8-36, 8-3
7, 8-38, 8-39, 8-40, 8-41, 8-42, 8-43, 8-44, 8-45,
8-46, 8-47, 8-48, 8-49, 8-50, 8-51, 8-52, 8-53, 8
-54, 8-55, 8-56, 8-57, 8-58, 8-59, 8-60, 8-61, 8-6
2, 8-63, 8-64, 8-65, 8-66, 8-67, 8-68, 8-69, 8-70,
8-71, 8-72, 8-73, 8-74, 8-75, 8-76, 8-77, 8-78, 8
-79, 8-80, 8-81, 8-82, 8-83, 8-84, 8-85, 8-86, 8-8
7, 8-88, 8-89, 8-90, 8-91, 8-92, 8-93, 8-94, 8-95,
8-96, 8-97,9-1, 9-2, 9-3, 9-4, 9-5, 9-6, 9-7, 9-
8, 9-9, 9-10, 9-11, 9-12, 9-13, 9-14, 9-15, 9-16,
9-17, 9-18, 9-19, 9-20, 9-21, 9-22, 9-23, 9-24, 9-
25, 9-26, 9-27, 9-28, 9-29, 9-30, 9-31, 9-32, 9-3
3, 9-34, 9-35, 9-36, 9-37, 9-38, 9-39, 9-40, 9-41,
9-42, 9-43, 9-44, 9-45, 9-46, 9-47, 9-48, 9-49, 9
-50, 9-51, 9-52, 9-53, 9-54, 9-55, 9-56, 9-57, 9-5
8, 9-59, 9-60, 9-61, 9-62, 9-63, 9-64, 9-65, 9-66,
9-67, 9-68, 9-69, 9-70, 9-71, 9-72, 9-73, 9-74, 9
-75, 9-76, 9-77, 9-78, 9-79, 9-80, 9-81, 9-82, 9-8
3, 9-84, 9-85, 9-86, 9-87, 9-88, 9-89, 9-90, 9-91,
9-92, 9-93, 9-94, 9-95, 9-96, 9-97,10-1, 10-2, 10
-3, 10-4, 10-5, 10-6, 10-7, 10-8, 10-9, 10-10, 10-
11, 10-12, 10-13, 10-14, 10-15, 10-16, 10-17, 10-1
8, 10-19, 10-20, 10-21, 10-22,10-23, 10-24, 10-25,
10-26, 10-27, 10-28, 10-29, 10-30, 10-31, 10-32,
10-33, 10-34, 10-35, 10-36, 10-37, 10-38, 10-39, 1
0-40, 10-41, 10-42, 10-43, 10-44, 10-45, 10-46, 10
-47, 10-48, 10-49, 10-50, 10-51, 10-52, 10-53, 10-
54, 10-55, 10-56, 10-57, 10-58, 10-59, 10-60, 10-6
1, 10-62, 10-63,10-64, 10-65, 10-66, 10-67, 10-68,
10-69, 10-70, 10-71, 10-72, 10-73, 10-74, 10-75,
10-76, 10-77, 10-78, 10-79, 10-80, 10-81, 10-82, 1
0-83, 10-84, 10-85, 10-86, 10-87, 10-88, 10-89, 10
-90, 10-91, 10-92, 10-93, 10-94,10-95, 10-96, 10-9
7,11-1, 11-2, 11-3, 11-4, 11-5, 11-6, 11-7, 11-8,
11-9, 11-10, 11-11, 11-12, 11-13, 11-14, 11-15, 11
-16, 11-17, 11-18, 11-19, 11-20, 11-21, 11-22,11-2
3, 11-24, 11-25, 11-26, 11-27, 11-28, 11-29, 11-3
0, 11-31, 11-32, 11-33, 11-34, 11-35, 11-36, 11-3
7, 11-38, 11-39, 11-40, 11-41, 11-42, 11-43, 11-4
4, 11-45, 11-46, 11-47, 11-48, 11-49, 11-50, 11-5
1, 11-52, 11-53, 11-54, 11-55, 11-56, 11-57, 11-5
8, 11-59, 11-60, 11-61, 11-62, 11-63,11-64, 11-65,
11-66, 11-67, 11-68, 11-69, 11-70, 11-71, 11-72,
11-73, 11-74, 11-75, 11-76, 11-77, 11-78, 11-79, 1
1-80, 11-81, 11-82, 11-83, 11-84, 11-85, 11-86, 11
-87, 11-88, 11-89, 11-90, 11-91, 11-92, 11-93, 11-
94,11-95, 11-96, 11-97,12-1, 12-2, 12-3, 12-4, 12-
5, 12-6, 12-7, 12-8, 12-9, 12-10, 12-11, 12-12, 12
-13, 12-14, 12-15, 12-16, 12-17, 12-18, 12-19, 12-
20, 12-21, 12-22, 12-23, 12-24, 12-25, 12-26, 12-2
7, 12-28, 12-29, 12-30, 12-31, 12-32, 12-33, 12-3
4, 12-35, 12-36, 12-37, 12-38, 12-39, 12-40, 12-4
1, 12-42, 12-43, 12-44, 12-45, 12-46, 12-47, 12-4
8, 12-49, 12-50, 12-51, 12-52, 12-53, 12-54, 12-5
5, 12-56, 12-57, 12-58, 12-59, 12-60, 12-61, 12-6
2, 12-63,12-64, 12-65, 12-66, 12-67, 12-68, 12-69,
12-70, 12-71, 12-72, 12-73, 12-74, 12-75, 12-76,
12-77, 12-78, 12-79, 12-80, 12-81, 12-82, 12-83, 1
2-84, 12-85, 12-86, 12-87, 12-88, 12-89, 12-90, 12
-91, 12-92, 12-93, 12-94,12-95, 12-96, 12-97,13-1,
13-2, 13-3, 13-4, 13-5, 13-6, 13-7, 13-8, 13-9, 1
3-10, 13-11, 13-12, 13-13, 13-14, 13-15, 13-16, 13
-17, 13-18, 13-19, 13-20, 13-21, 13-22, 13-23, 13-2
4, 13-25, 13-26, 13-27, 13-28, 13-29, 13-30, 13-3
1, 13-32, 13-33, 13-34, 13-35, 13-36, 13-37, 13-3
8, 13-39, 13-40, 13-41, 13-42, 13-43, 13-44, 13-4
5, 13-46, 13-47, 13-48, 13-49, 13-50, 13-51, 13-5
2, 13-53, 13-54, 13-55, 13-56, 13-57, 13-58, 13-5
9, 13-60, 13-61, 13-62, 13-63,13-64, 13-65, 13-66,
13-67, 13-68, 13-69, 13-70, 13-71, 13-72, 13-73,
13-74, 13-75, 13-76, 13-77, 13-78, 13-79, 13-80, 1
3-81, 13-82, 13-83, 13-84, 13-85, 13-86, 13-87, 13
-88, 13-89, 13-90, 13-91, 13-92, 13-93, 13-94,13-9
5, 13-96, 13-97,14-1, 14-2, 14-3, 14-4, 14-5, 14-
6, 14-7, 14-8, 14-9, 14-10, 14-11, 14-12, 14-13, 1
4-14, 14-15, 14-16, 14-17, 14-18, 14-19, 14-20, 14
-21, 14-22, 14-23, 14-24, 14-25, 14-26, 14-27, 14-2
8, 14-29, 14-30, 14-31, 14-32, 14-33, 14-34, 14-3
5, 14-36, 14-37, 14-38, 14-39, 14-40, 14-41, 14-4
2, 14-43, 14-44, 14-45, 14-46, 14-47, 14-48, 14-4
9, 14-50, 14-51, 14-52, 14-53, 14-54, 14-55, 14-5
6, 14-57, 14-58, 14-59, 14-60, 14-61, 14-62, 14-6
3,14-64, 14-65, 14-66, 14-67, 14-68, 14-69, 14-70,
14-71, 14-72, 14-73, 14-74, 14-75, 14-76, 14-77,
14-78, 14-79, 14-80, 14-81, 14-82, 14-83, 14-84, 1
4-85, 14-86, 14-87, 14-88, 14-89, 14-90, 14-91, 14
-92, 14-93, 14-94,14-95, 14-96, 14-97,15-1, 15-2,
15-3, 15-4, 15-5, 15-6, 15-7, 15-8, 15-9, 15-10, 1
5-11, 15-12, 15-13, 15-14, 15-15, 15-16, 15-17, 15
-18, 15-19, 15-20, 15-21, 15-22,15-23, 15-24, 15-2
5, 15-26, 15-27, 15-28, 15-29, 15-30, 15-31, 15-3
2, 15-33, 15-34, 15-35, 15-36, 15-37, 15-38, 15-3
9, 15-40, 15-41, 15-42, 15-43, 15-44, 15-45, 15-4
6, 15-47, 15-48, 15-49, 15-50, 15-51, 15-52, 15-5
3, 15-54, 15-55, 15-56, 15-57, 15-58, 15-59, 15-6
0, 15-61, 15-62, 15-63,15-64, 15-65, 15-66, 15-67,
15-68, 15-69, 15-70, 15-71, 15-72, 15-73, 15-74,
15-75, 15-76, 15-77, 15-78, 15-79, 15-80, 15-81, 1
5-82, 15-83, 15-84, 15-85, 15-86, 15-87, 15-88, 15
-89, 15-90, 15-91, 15-92, 15-93, 15-94,15-95, 15-9
6, 15-97,16-1, 16-2, 16-3, 16-4, 16-5, 16-6, 16-7,
16-8, 16-9, 16-10, 16-11, 16-12, 16-13, 16-14, 16
-15, 16-16, 16-17, 16-18, 16-19, 16-20, 16-21, 16-
22,16-23, 16-24, 16-25, 16-26, 16-27, 16-28, 16-2
9, 16-30, 16-31, 16-32, 16-33, 16-34, 16-35, 16-3
6, 16-37, 16-38, 16-39, 16-40, 16-41, 16-42, 16-4
3, 16-44, 16-45, 16-46, 16-47, 16-48, 16-49, 16-5
0, 16-51, 16-52, 16-53, 16-54, 16-55, 16-56, 16-5
7, 16-58, 16-59, 16-60, 16-61, 16-62, 16-63,16-64,
16-65, 16-66, 16-67, 16-68, 16-69, 16-70, 16-71,
16-72, 16-73, 16-74, 16-75, 16-76, 16-77, 16-78, 1
6-79, 16-80, 16-81, 16-82, 16-83, 16-84, 16-85, 16
-86, 16-87, 16-88, 16-89, 16-90, 16-91, 16-92, 16-
93, 16-94, 16-95, 16-96, 16-97,17-1, 17-2, 17-3, 17
-4, 17-5, 17-6, 17-7, 17-8, 17-9, 17-10, 17-11, 17
-12, 17-13, 17-14, 17-15, 17-16, 17-17, 17-18, 17-
19, 17-20, 17-21, 17-22, 17-23, 17-24, 17-25, 17-2
6, 17-27, 17-28, 17-29, 17-30, 17-31, 17-32, 17-3
3, 17-34, 17-35, 17-36, 17-37, 17-38, 17-39, 17-4
0, 17-41, 17-42, 17-43, 17-44, 17-45, 17-46, 17-4
7, 17-48, 17-49, 17-50, 17-51, 17-52, 17-53, 17-5
4, 17-55, 17-56, 17-57, 17-58, 17-59, 17-60, 17-6
1, 17-62, 17-63,17-64, 17-65, 17-66, 17-67, 17-68,
17-69, 17-70, 17-71, 17-72, 17-73, 17-74, 17-75,
17-76, 17-77, 17-78, 17-79, 17-80, 17-81, 17-82, 1
7-83, 17-84, 17-85, 17-86, 17-87, 17-88, 17-89, 17
-90, 17-91, 17-92, 17-93, 17-94,17-95, 17-96, 17-9
7,18-1, 18-2, 18-3, 18-4, 18-5, 18-6, 18-7, 18-8,
18-9, 18-10, 18-11, 18-12, 18-13, 18-14, 18-15, 18
-16, 18-17, 18-18, 18-19, 18-20, 18-21, 18-22, 18-2
3, 18-24, 18-25, 18-26, 18-27, 18-28, 18-29, 18-3
0, 18-31, 18-32, 18-33, 18-34, 18-35, 18-36, 18-3
7, 18-38, 18-39, 18-40, 18-41, 18-42, 18-43, 18-4
4, 18-45, 18-46, 18-47, 18-48, 18-49, 18-50, 18-5
1, 18-52, 18-53, 18-54, 18-55, 18-56, 18-57, 18-5
8, 18-59, 18-60, 18-61, 18-62, 18-63,18-64, 18-65,
18-66, 18-67, 18-68, 18-69, 18-70, 18-71, 18-72,
18-73, 18-74, 18-75, 18-76, 18-77, 18-78, 18-79, 1
8-80, 18-81, 18-82, 18-83, 18-84, 18-85, 18-86, 18
-87, 18-88, 18-89, 18-90, 18-91, 18-92, 18-93, 18-
94,18-95, 18-96, 18-97,19-1, 19-2, 19-3, 19-4, 19-
5, 19-6, 19-7, 19-8, 19-9, 19-10, 19-11, 19-12, 19
-13, 19-14, 19-15, 19-16, 19-17, 19-18, 19-19, 19-
20, 19-21, 19-22, 19-23, 19-24, 19-25, 19-26, 19-2
7, 19-28, 19-29, 19-30, 19-31, 19-32, 19-33, 19-3
4, 19-35, 19-36, 19-37, 19-38, 19-39, 19-40, 19-4
1, 19-42, 19-43, 19-44, 19-45, 19-46, 19-47, 19-4
8, 19-49, 19-50, 19-51, 19-52, 19-53, 19-54, 19-5
5, 19-56, 19-57, 19-58, 19-59, 19-60, 19-61, 19-6
2, 19-63,19-64, 19-65, 19-66, 19-67, 19-68, 19-69,
19-70, 19-71, 19-72, 19-73, 19-74, 19-75, 19-76,
19-77, 19-78, 19-79, 19-80, 19-81, 19-82, 19-83, 1
9-84, 19-85, 19-86, 19-87, 19-88, 19-89, 19-90, 19
-91, 19-92, 19-93, 19-94,19-95, 19-96, 19-97,20-1,
20-2, 20-3, 20-4, 20-5, 20-6, 20-7, 20-8, 20-9, 2
0-10, 20-11, 20-12, 20-13, 20-14, 20-15, 20-16, 20
-17, 20-18, 20-19, 20-20, 20-21, 20-22, 20-23, 20-2
4, 20-25, 20-26, 20-27, 20-28, 20-29, 20-30, 20-3
1, 20-32, 20-33, 20-34, 20-35, 20-36, 20-37, 20-3
8, 20-39, 20-40, 20-41, 20-42, 20-43, 20-44, 20-4
5, 20-46, 20-47, 20-48, 20-49, 20-50, 20-51, 20-5
2, 20-53, 20-54, 20-55, 20-56, 20-57, 20-58, 20-5
9, 20-60, 20-61, 20-62, 20-63,20-64, 20-65, 20-66,
20-67, 20-68, 20-69, 20-70, 20-71, 20-72, 20-73,
20-74, 20-75, 20-76, 20-77, 20-78, 20-79, 20-80, 2
0-81, 20-82, 20-83, 20-84, 20-85, 20-86, 20-87, 20
-88, 20-89, 20-90, 20-91, 20-92, 20-93, 20-94,20-9
5, 20-96, 20-97,21-1, 21-2, 21-3, 21-4, 21-5, 21-
6, 21-7, 21-8, 21-9, 21-10, 21-11, 21-12, 21-13, 2
1-14, 21-15, 21-16, 21-17, 21-18, 21-19, 21-20, 21
-21, 21-22, 21-23, 21-24, 21-25, 21-26, 21-27, 21-2
8, 21-29, 21-30, 21-31, 21-32, 21-33, 21-34, 21-3
5, 21-36, 21-37, 21-38, 21-39, 21-40, 21-41, 21-4
2, 21-43, 21-44, 21-45, 21-46, 21-47, 21-48, 21-4
9, 21-50, 21-51, 21-52, 21-53, 21-54, 21-55, 21-5
6, 21-57, 21-58, 21-59, 21-60, 21-61, 21-62, 21-6
3,21-64, 21-65, 21-66, 21-67, 21-68, 21-69, 21-70,
21-71, 21-72, 21-73, 21-74, 21-75, 21-76, 21-77,
21-78, 21-79, 21-80, 21-81, 21-82, 21-83, 21-84, 2
1-85, 21-86, 21-87, 21-88, 21-89, 21-90, 21-91, 21
-92, 21-93, 21-94,21-95, 21-96, 21-97,22-1, 22-2,
22-3, 22-4, 22-5, 22-6, 22-7, 22-8, 22-9, 22-10, 2
2-11, 22-12, 22-13, 22-14, 22-15, 22-16, 22-17, 22
-18, 22-19, 22-20, 22-21, 22-22,22-23, 22-24, 22-2
5, 22-26, 22-27, 22-28, 22-29, 22-30, 22-31, 22-3
2, 22-33, 22-34, 22-35, 22-36, 22-37, 22-38, 22-3
9, 22-40, 22-41, 22-42, 22-43, 22-44, 22-45, 22-4
6, 22-47, 22-48, 22-49, 22-50, 22-51, 22-52, 22-5
3, 22-54, 22-55, 22-56, 22-57, 22-58, 22-59, 22-6
0, 22-61, 22-62, 22-63,22-64, 22-65, 22-66, 22-67,
22-68, 22-69, 22-70, 22-71, 22-72, 22-73, 22-74,
22-75, 22-76, 22-77, 22-78, 22-79, 22-80, 22-81, 2
2-82, 22-83, 22-84, 22-85, 22-86, 22-87, 22-88, 22
-89, 22-90, 22-91, 22-92, 22-93, 22-94,22-95, 22-9
6, 22-97,23-1, 23-2, 23-3, 23-4, 23-5, 23-6, 23-7,
23-8, 23-9, 23-10, 23-11, 23-12, 23-13, 23-14, 23
-15, 23-16, 23-17, 23-18, 23-19, 23-20, 23-21, 23-
22,23-23, 23-24, 23-25, 23-26, 23-27, 23-28, 23-2
9, 23-30, 23-31, 23-32, 23-33, 23-34, 23-35, 23-3
6, 23-37, 23-38, 23-39, 23-40, 23-41, 23-42, 23-4
3, 23-44, 23-45, 23-46, 23-47, 23-48, 23-49, 23-5
0, 23-51, 23-52, 23-53, 23-54, 23-55, 23-56, 23-5
7, 23-58, 23-59, 23-60, 23-61, 23-62, 23-63,23-64,
23-65, 23-66, 23-67, 23-68, 23-69, 23-70, 23-71,
23-72, 23-73, 23-74, 23-75, 23-76, 23-77, 23-78, 2
3-79, 23-80, 23-81, 23-82, 23-83, 23-84, 23-85, 23
-86, 23-87, 23-88, 23-89, 23-90, 23-91, 23-92, 23-
93, 23-94, 23-95, 23-96, 23-97,24-1, 24-2, 24-3, 24
-4, 24-5, 24-6, 24-7, 24-8, 24-9, 24-10, 24-11, 24
-12, 24-13, 24-14, 24-15, 24-16, 24-17, 24-18, 24-
19, 24-20, 24-21, 24-22,24-23, 24-24, 24-25, 24-2
6, 24-27, 24-28, 24-29, 24-30, 24-31, 24-32, 24-3
3, 24-34, 24-35, 24-36, 24-37, 24-38, 24-39, 24-4
0, 24-41, 24-42, 24-43, 24-44, 24-45, 24-46, 24-4
7, 24-48, 24-49, 24-50, 24-51, 24-52, 24-53, 24-5
4, 24-55, 24-56, 24-57, 24-58, 24-59, 24-60, 24-6
1, 24-62, 24-63, 24-64, 24-65, 24-66, 24-67, 24-68,
24-69, 24-70, 24-71, 24-72, 24-73, 24-74, 24-75,
24-76, 24-77, 24-78, 24-79, 24-80, 24-81, 24-82, 2
4-83, 24-84, 24-85, 24-86, 24-87, 24-88, 24-89, 24
-90, 24-91, 24-92, 24-93, 24-94,24-95, 24-96, 24-9
7,25-1, 25-2, 25-3, 25-4, 25-5, 25-6, 25-7, 25-8,
25-9, 25-10, 25-11, 25-12, 25-13, 25-14, 25-15, 25
-16, 25-17, 25-18, 25-19, 25-20, 25-21, 25-22,25-2
3, 25-24, 25-25, 25-26, 25-27, 25-28, 25-29, 25-3
0, 25-31, 25-32, 25-33, 25-34, 25-35, 25-36, 25-3
7, 25-38, 25-39, 25-40, 25-41, 25-42, 25-43, 25-4
4, 25-45, 25-46, 25-47, 25-48, 25-49, 25-50, 25-5
1, 25-52, 25-53, 25-54, 25-55, 25-56, 25-57, 25-5
8, 25-59, 25-60, 25-61, 25-62, 25-63,25-64, 25-65,
25-66, 25-67, 25-68, 25-69, 25-70, 25-71, 25-72,
25-73, 25-74, 25-75, 25-76, 25-77, 25-78, 25-79, 2
5-80, 25-81, 25-82, 25-83, 25-84, 25-85, 25-86, 25
-87, 25-88, 25-89, 25-90, 25-91, 25-92, 25-93, 25-
94,25-95, 25-96, 25-97,26-1, 26-2, 26-3, 26-4, 26-
5, 26-6, 26-7, 26-8, 26-9, 26-10, 26-11, 26-12, 26
-13, 26-14, 26-15, 26-16, 26-17, 26-18, 26-19, 26-
20, 26-21, 26-22, 26-23, 26-24, 26-25, 26-26, 26-2
7, 26-28, 26-29, 26-30, 26-31, 26-32, 26-33, 26-3
4, 26-35, 26-36, 26-37, 26-38, 26-39, 26-40, 26-4
1, 26-42, 26-43, 26-44, 26-45, 26-46, 26-47, 26-4
8, 26-49, 26-50, 26-51, 26-52, 26-53, 26-54, 26-5
5, 26-56, 26-57, 26-58, 26-59, 26-60, 26-61, 26-6
2, 26-63,26-64, 26-65, 26-66, 26-67, 26-68, 26-69,
26-70, 26-71, 26-72, 26-73, 26-74, 26-75, 26-76,
26-77, 26-78, 26-79, 26-80, 26-81, 26-82, 26-83, 2
6-84, 26-85, 26-86, 26-87, 26-88, 26-89, 26-90, 26
-91, 26-92, 26-93, 26-94,26-95, 26-96, 26-97,27-1,
27-2, 27-3, 27-4, 27-5, 27-6, 27-7, 27-8, 27-9, 2
7-10, 27-11, 27-12, 27-13, 27-14, 27-15, 27-16, 27
-17, 27-18, 27-19, 27-20, 27-21, 27-22, 27-23, 27-2
4, 27-25, 27-26, 27-27, 27-28, 27-29, 27-30, 27-3
1, 27-32, 27-33, 27-34, 27-35, 27-36, 27-37, 27-3
8, 27-39, 27-40, 27-41, 27-42, 27-43, 27-44, 27-4
5, 27-46, 27-47, 27-48, 27-49, 27-50, 27-51, 27-5
2, 27-53, 27-54, 27-55, 27-56, 27-57, 27-58, 27-5
9, 27-60, 27-61, 27-62, 27-63,27-64, 27-65, 27-66,
27-67, 27-68, 27-69, 27-70, 27-71, 27-72, 27-73,
27-74, 27-75, 27-76, 27-77, 27-78, 27-79, 27-80, 2
7-81, 27-82, 27-83, 27-84, 27-85, 27-86, 27-87, 27
-88, 27-89, 27-90, 27-91, 27-92, 27-93, 27-94,27-9
5, 27-96, 27-97,28-1, 28-2, 28-3, 28-4, 28-5, 28-
6, 28-7, 28-8, 28-9, 28-10, 28-11, 28-12, 28-13, 2
8-14, 28-15, 28-16, 28-17, 28-18, 28-19, 28-20, 28
-21, 28-22, 28-23, 28-24, 28-25, 28-26, 28-27, 28-2
8, 28-29, 28-30, 28-31, 28-32, 28-33, 28-34, 28-3
5, 28-36, 28-37, 28-38, 28-39, 28-40, 28-41, 28-4
2, 28-43, 28-44, 28-45, 28-46, 28-47, 28-48, 28-4
9, 28-50, 28-51, 28-52, 28-53, 28-54, 28-55, 28-5
6, 28-57, 28-58, 28-59, 28-60, 28-61, 28-62, 28-6
3,28-64, 28-65, 28-66, 28-67, 28-68, 28-69, 28-70,
28-71, 28-72, 28-73, 28-74, 28-75, 28-76, 28-77,
28-78, 28-79, 28-80, 28-81, 28-82, 28-83, 28-84, 2
8-85, 28-86, 28-87, 28-88, 28-89, 28-90, 28-91, 28
-92, 28-93, 28-94,28-95, 28-96, 28-97,29-1, 29-2,
29-3, 29-4, 29-5, 29-6, 29-7, 29-8, 29-9, 29-10, 2
9-11, 29-12, 29-13, 29-14, 29-15, 29-16, 29-17, 29
-18, 29-19, 29-20, 29-21, 29-22,29-23, 29-24, 29-2
5, 29-26, 29-27, 29-28, 29-29, 29-30, 29-31, 29-3
2, 29-33, 29-34, 29-35, 29-36, 29-37, 29-38, 29-3
9, 29-40, 29-41, 29-42, 29-43, 29-44, 29-45, 29-4
6, 29-47, 29-48, 29-49, 29-50, 29-51, 29-52, 29-5
3, 29-54, 29-55, 29-56, 29-57, 29-58, 29-59, 29-6
0, 29-61, 29-62, 29-63, 29-64, 29-65, 29-66, 29-67,
29-68, 29-69, 29-70, 29-71, 29-72, 29-73, 29-74,
29-75, 29-76, 29-77, 29-78, 29-79, 29-80, 29-81, 2
9-82, 29-83, 29-84, 29-85, 29-86, 29-87, 29-88, 29
-89, 29-90, 29-91, 29-92, 29-93, 29-94,29-95, 29-9
6, 29-97,30-1, 30-2, 30-3, 30-4, 30-5, 30-6, 30-7,
30-8, 30-9, 30-10, 30-11, 30-12, 30-13, 30-14, 30
-15, 30-16, 30-17, 30-18, 30-19, 30-20, 30-21, 30-
22,30-23, 30-24, 30-25, 30-26, 30-27, 30-28, 30-2
9, 30-30, 30-31, 30-32, 30-33, 30-34, 30-35, 30-3
6, 30-37, 30-38, 30-39, 30-40, 30-41, 30-42, 30-4
3, 30-44, 30-45, 30-46, 30-47, 30-48, 30-49, 30-5
0, 30-51, 30-52, 30-53, 30-54, 30-55, 30-56, 30-5
7, 30-58, 30-59, 30-60, 30-61, 30-62, 30-63,30-64,
30-65, 30-66, 30-67, 30-68, 30-69, 30-70, 30-71,
30-72, 30-73, 30-74, 30-75, 30-76, 30-77, 30-78, 3
0-79, 30-80, 30-81, 30-82, 30-83, 30-84, 30-85, 30
-86, 30-87, 30-88, 30-89, 30-90, 30-91, 30-92, 30-
93, 30-94, 30-95, 30-96, 30-97,31-1, 31-2, 31-3, 31
-4, 31-5, 31-6, 31-7, 31-8, 31-9, 31-10, 31-11, 31
-12, 31-13, 31-14, 31-15, 31-16, 31-17, 31-18, 31-
19, 31-20, 31-21, 31-22, 31-23, 31-24, 31-25, 31-2
6, 31-27, 31-28, 31-29, 31-30, 31-31, 31-32, 31-3
3, 31-34, 31-35, 31-36, 31-37, 31-38, 31-39, 31-4
0, 31-41, 31-42, 31-43, 31-44, 31-45, 31-46, 31-4
7, 31-48, 31-49, 31-50, 31-51, 31-52, 31-53, 31-5
4, 31-55, 31-56, 31-57, 31-58, 31-59, 31-60, 31-6
1, 31-62, 31-63, 31-64, 31-65, 31-66, 31-67, 31-68,
31-69, 31-70, 31-71, 31-72, 31-73, 31-74, 31-75,
31-76, 31-77, 31-78, 31-79, 31-80, 31-81, 31-82, 3
1-83, 31-84, 31-85, 31-86, 31-87, 31-88, 31-89, 31
-90, 31-91, 31-92, 31-93, 31-94,31-95, 31-96, 31-9
7,32-1, 32-2, 32-3, 32-4, 32-5, 32-6, 32-7, 32-8,
32-9, 32-10, 32-11, 32-12, 32-13, 32-14, 32-15, 32
-16, 32-17, 32-18, 32-19, 32-20, 32-21, 32-22, 32-2
3, 32-24, 32-25, 32-26, 32-27, 32-28, 32-29, 32-3
0, 32-31, 32-32, 32-33, 32-34, 32-35, 32-36, 32-3
7, 32-38, 32-39, 32-40, 32-41, 32-42, 32-43, 32-4
4, 32-45, 32-46, 32-47, 32-48, 32-49, 32-50, 32-5
1, 32-52, 32-53, 32-54, 32-55, 32-56, 32-57, 32-5
8, 32-59, 32-60, 32-61, 32-62, 32-63, 32-64, 32-65,
32-66, 32-67, 32-68, 32-69, 32-70, 32-71, 32-72,
32-73, 32-74, 32-75, 32-76, 32-77, 32-78, 32-79, 3
2-80, 32-81, 32-82, 32-83, 32-84, 32-85, 32-86, 32
-87, 32-88, 32-89, 32-90, 32-91, 32-92, 32-93, 32-
94,32-95, 32-96, 32-97,33-1, 33-2, 33-3, 33-4, 33-
5, 33-6, 33-7, 33-8, 33-9, 33-10, 33-11, 33-12, 33
-13, 33-14, 33-15, 33-16, 33-17, 33-18, 33-19, 33-
20, 33-21, 33-22, 33-23, 33-24, 33-25, 33-26, 33-2
7, 33-28, 33-29, 33-30, 33-31, 33-32, 33-33, 33-3
4, 33-35, 33-36, 33-37, 33-38, 33-39, 33-40, 33-4
1, 33-42, 33-43, 33-44, 33-45, 33-46, 33-47, 33-4
8, 33-49, 33-50, 33-51, 33-52, 33-53, 33-54, 33-5
5, 33-56, 33-57, 33-58, 33-59, 33-60, 33-61, 33-6
2, 33-63,33-64, 33-65, 33-66, 33-67, 33-68, 33-69,
33-70, 33-71, 33-72, 33-73, 33-74, 33-75, 33-76,
33-77, 33-78, 33-79, 33-80, 33-81, 33-82, 33-83, 3
3-84, 33-85, 33-86, 33-87, 33-88, 33-89, 33-90, 33
-91, 33-92, 33-93, 33-94,33-95, 33-96, 33-97,34-1,
34-2, 34-3, 34-4, 34-5, 34-6, 34-7, 34-8, 34-9, 3
4-10, 34-11, 34-12, 34-13, 34-14, 34-15, 34-16, 34
-17, 34-18, 34-19, 34-20, 34-21, 34-22, 34-23, 34-2
4, 34-25, 34-26, 34-27, 34-28, 34-29, 34-30, 34-3
1, 34-32, 34-33, 34-34, 34-35, 34-36, 34-37, 34-3
8, 34-39, 34-40, 34-41, 34-42, 34-43, 34-44, 34-4
5, 34-46, 34-47, 34-48, 34-49, 34-50, 34-51, 34-5
2, 34-53, 34-54, 34-55, 34-56, 34-57, 34-58, 34-5
9, 34-60, 34-61, 34-62, 34-63,34-64, 34-65, 34-66,
34-67, 34-68, 34-69, 34-70, 34-71, 34-72, 34-73,
34-74, 34-75, 34-76, 34-77, 34-78, 34-79, 34-80, 3
4-81, 34-82, 34-83, 34-84, 34-85, 34-86, 34-87, 34
-88, 34-89, 34-90, 34-91, 34-92, 34-93, 34-94,34-9
5, 34-96, 34-97,35-1, 35-2, 35-3, 35-4, 35-5, 35-
6, 35-7, 35-8, 35-9, 35-10, 35-11, 35-12, 35-13, 3
5-14, 35-15, 35-16, 35-17, 35-18, 35-19, 35-20, 35
-21, 35-22, 35-23, 35-24, 35-25, 35-26, 35-27, 35-2
8, 35-29, 35-30, 35-31, 35-32, 35-33, 35-34, 35-3
5, 35-36, 35-37, 35-38, 35-39, 35-40, 35-41, 35-4
2, 35-43, 35-44, 35-45, 35-46, 35-47, 35-48, 35-4
9, 35-50, 35-51, 35-52, 35-53, 35-54, 35-55, 35-5
6, 35-57, 35-58, 35-59, 35-60, 35-61, 35-62, 35-6
3,35-64, 35-65, 35-66, 35-67, 35-68, 35-69, 35-70,
35-71, 35-72, 35-73, 35-74, 35-75, 35-76, 35-77,
35-78, 35-79, 35-80, 35-81, 35-82, 35-83, 35-84, 3
5-85, 35-86, 35-87, 35-88, 35-89, 35-90, 35-91, 35
-92, 35-93, 35-94,35-95, 35-96, 35-97,36-1, 36-2,
36-3, 36-4, 36-5, 36-6, 36-7, 36-8, 36-9, 36-10, 3
6-11, 36-12, 36-13, 36-14, 36-15, 36-16, 36-17, 36
-18, 36-19, 36-20, 36-21, 36-22,36-23, 36-24, 36-2
5, 36-26, 36-27, 36-28, 36-29, 36-30, 36-31, 36-3
2, 36-33, 36-34, 36-35, 36-36, 36-37, 36-38, 36-3
9, 36-40, 36-41, 36-42, 36-43, 36-44, 36-45, 36-4
6, 36-47, 36-48, 36-49, 36-50, 36-51, 36-52, 36-5
3, 36-54, 36-55, 36-56, 36-57, 36-58, 36-59, 36-6
0, 36-61, 36-62, 36-63,36-64, 36-65, 36-66, 36-67,
36-68, 36-69, 36-70, 36-71, 36-72, 36-73, 36-74,
36-75, 36-76, 36-77, 36-78, 36-79, 36-80, 36-81, 3
6-82, 36-83, 36-84, 36-85, 36-86, 36-87, 36-88, 36
-89, 36-90, 36-91, 36-92, 36-93, 36-94,36-95, 36-9
6, 36-97, 37-1, 37-2, 37-3, 37-4, 37-5, 37-6, 37-7,
37-8, 37-9, 37-10, 37-11, 37-12, 37-13, 37-14, 37
-15, 37-16, 37-17, 37-18, 37-19, 37-20, 37-21, 37-
22,37-23, 37-24, 37-25, 37-26, 37-27, 37-28, 37-2
9, 37-30, 37-31, 37-32, 37-33, 37-34, 37-35, 37-3
6, 37-37, 37-38, 37-39, 37-40, 37-41, 37-42, 37-4
3, 37-44, 37-45, 37-46, 37-47, 37-48, 37-49, 37-5
0, 37-51, 37-52, 37-53, 37-54, 37-55, 37-56, 37-5
7, 37-58, 37-59, 37-60, 37-61, 37-62, 37-63,37-64,
37-65, 37-66, 37-67, 37-68, 37-69, 37-70, 37-71,
37-72, 37-73, 37-74, 37-75, 37-76, 37-77, 37-78, 3
7-79, 37-80, 37-81, 37-82, 37-83, 37-84, 37-85, 37
-86, 37-87, 37-88, 37-89, 37-90, 37-91, 37-92, 37-
93, 37-94, 37-95, 37-96, 37-97,38-1, 38-2, 38-3, 38
-4, 38-5, 38-6, 38-7, 38-8, 38-9, 38-10, 38-11, 38
-12, 38-13, 38-14, 38-15, 38-16, 38-17, 38-18, 38-
19, 38-20, 38-21, 38-22, 38-23, 38-24, 38-25, 38-2
6, 38-27, 38-28, 38-29, 38-30, 38-31, 38-32, 38-3
3, 38-34, 38-35, 38-36, 38-37, 38-38, 38-39, 38-4
0, 38-41, 38-42, 38-43, 38-44, 38-45, 38-46, 38-4
7, 38-48, 38-49, 38-50, 38-51, 38-52, 38-53, 38-5
4, 38-55, 38-56, 38-57, 38-58, 38-59, 38-60, 38-6
1, 38-62, 38-63,38-64, 38-65, 38-66, 38-67, 38-68,
38-69, 38-70, 38-71, 38-72, 38-73, 38-74, 38-75,
38-76, 38-77, 38-78, 38-79, 38-80, 38-81, 38-82, 3
8-83, 38-84, 38-85, 38-86, 38-87, 38-88, 38-89, 38
-90, 38-91, 38-92, 38-93, 38-94,38-95, 38-96, 38-9
7,39-1, 39-2, 39-3, 39-4, 39-5, 39-6, 39-7, 39-8,
39-9, 39-10, 39-11, 39-12, 39-13, 39-14, 39-15, 39
-16, 39-17, 39-18, 39-19, 39-20, 39-21, 39-22, 39-2
3, 39-24, 39-25, 39-26, 39-27, 39-28, 39-29, 39-3
0, 39-31, 39-32, 39-33, 39-34, 39-35, 39-36, 39-3
7, 39-38, 39-39, 39-40, 39-41, 39-42, 39-43, 39-4
4, 39-45, 39-46, 39-47, 39-48, 39-49, 39-50, 39-5
1, 39-52, 39-53, 39-54, 39-55, 39-56, 39-57, 39-5
8, 39-59, 39-60, 39-61, 39-62, 39-63,39-64, 39-65,
39-66, 39-67, 39-68, 39-69, 39-70, 39-71, 39-72,
39-73, 39-74, 39-75, 39-76, 39-77, 39-78, 39-79, 3
9-80, 39-81, 39-82, 39-83, 39-84, 39-85, 39-86, 39
-87, 39-88, 39-89, 39-90, 39-91, 39-92, 39-93, 39-
94,39-95, 39-96, 39-97,40-1, 40-2, 40-3, 40-4, 40-
5, 40-6, 40-7, 40-8, 40-9, 40-10, 40-11, 40-12, 40
-13, 40-14, 40-15, 40-16, 40-17, 40-18, 40-19, 40-
20, 40-21, 40-22, 40-23, 40-24, 40-25, 40-26, 40-2
7, 40-28, 40-29, 40-30, 40-31, 40-32, 40-33, 40-3
4, 40-35, 40-36, 40-37, 40-38, 40-39, 40-40, 40-4
1, 40-42, 40-43, 40-44, 40-45, 40-46, 40-47, 40-4
8, 40-49, 40-50, 40-51, 40-52, 40-53, 40-54, 40-5
5, 40-56, 40-57, 40-58, 40-59, 40-60, 40-61, 40-6
2, 40-63,40-64, 40-65, 40-66, 40-67, 40-68, 40-69,
40-70, 40-71, 40-72, 40-73, 40-74, 40-75, 40-76,
40-77, 40-78, 40-79, 40-80, 40-81, 40-82, 40-83, 4
0-84, 40-85, 40-86, 40-87, 40-88, 40-89, 40-90, 40
-91, 40-92, 40-93, 40-94,40-95, 40-96, 40-97,41-1,
41-2, 41-3, 41-4, 41-5, 41-6, 41-7, 41-8, 41-9, 4
1-10, 41-11, 41-12, 41-13, 41-14, 41-15, 41-16, 41
-17, 41-18, 41-19, 41-20, 41-21, 41-22, 41-23, 41-2
4, 41-25, 41-26, 41-27, 41-28, 41-29, 41-30, 41-3
1, 41-32, 41-33, 41-34, 41-35, 41-36, 41-37, 41-3
8, 41-39, 41-40, 41-41, 41-42, 41-43, 41-44, 41-4
5, 41-46, 41-47, 41-48, 41-49, 41-50, 41-51, 41-5
2, 41-53, 41-54, 41-55, 41-56, 41-57, 41-58, 41-5
9, 41-60, 41-61, 41-62, 41-63,41-64, 41-65, 41-66,
41-67, 41-68, 41-69, 41-70, 41-71, 41-72, 41-73,
41-74, 41-75, 41-76, 41-77, 41-78, 41-79, 41-80, 4
1-81, 41-82, 41-83, 41-84, 41-85, 41-86, 41-87, 41
-88, 41-89, 41-90, 41-91, 41-92, 41-93, 41-94,41-9
5, 41-96, 41-97,42-1, 42-2, 42-3, 42-4, 42-5, 42-
6, 42-7, 42-8, 42-9, 42-10, 42-11, 42-12, 42-13, 4
2-14, 42-15, 42-16, 42-17, 42-18, 42-19, 42-20, 42
-21, 42-22, 42-23, 42-24, 42-25, 42-26, 42-27, 42-2
8, 42-29, 42-30, 42-31, 42-32, 42-33, 42-34, 42-3
5, 42-36, 42-37, 42-38, 42-39, 42-40, 42-41, 42-4
2, 42-43, 42-44, 42-45, 42-46, 42-47, 42-48, 42-4
9, 42-50, 42-51, 42-52, 42-53, 42-54, 42-55, 42-5
6, 42-57, 42-58, 42-59, 42-60, 42-61, 42-62, 42-6
3,42-64, 42-65, 42-66, 42-67, 42-68, 42-69, 42-70,
42-71, 42-72, 42-73, 42-74, 42-75, 42-76, 42-77,
42-78, 42-79, 42-80, 42-81, 42-82, 42-83, 42-84, 4
2-85, 42-86, 42-87, 42-88, 42-89, 42-90, 42-91, 42
-92, 42-93, 42-94,42-95, 42-96, 42-97,43-1, 43-2,
43-3, 43-4, 43-5, 43-6, 43-7, 43-8, 43-9, 43-10, 4
3-11, 43-12, 43-13, 43-14, 43-15, 43-16, 43-17, 43
-18, 43-19, 43-20, 43-21, 43-22, 43-23, 43-24, 43-2
5, 43-26, 43-27, 43-28, 43-29, 43-30, 43-31, 43-3
2, 43-33, 43-34, 43-35, 43-36, 43-37, 43-38, 43-3
9, 43-40, 43-41, 43-42, 43-43, 43-44, 43-45, 43-4
6, 43-47, 43-48, 43-49, 43-50, 43-51, 43-52, 43-5
3, 43-54, 43-55, 43-56, 43-57, 43-58, 43-59, 43-6
0, 43-61, 43-62, 43-63, 43-64, 43-65, 43-66, 43-67,
43-68, 43-69, 43-70, 43-71, 43-72, 43-73, 43-74,
43-75, 43-76, 43-77, 43-78, 43-79, 43-80, 43-81, 4
3-82, 43-83, 43-84, 43-85, 43-86, 43-87, 43-88, 43
-89, 43-90, 43-91, 43-92, 43-93, 43-94,43-95, 43-9
6, 43-97,44-1, 44-2, 44-3, 44-4, 44-5, 44-6, 44-7,
44-8, 44-9, 44-10, 44-11, 44-12, 44-13, 44-14, 44
-15, 44-16, 44-17, 44-18, 44-19, 44-20, 44-21, 44-
22,44-23, 44-24, 44-25, 44-26, 44-27, 44-28, 44-2
9, 44-30, 44-31, 44-32, 44-33, 44-34, 44-35, 44-3
6, 44-37, 44-38, 44-39, 44-40, 44-41, 44-42, 44-4
3, 44-44, 44-45, 44-46, 44-47, 44-48, 44-49, 44-5
0, 44-51, 44-52, 44-53, 44-54, 44-55, 44-56, 44-5
7, 44-58, 44-59, 44-60, 44-61, 44-62, 44-63,44-64,
44-65, 44-66, 44-67, 44-68, 44-69, 44-70, 44-71,
44-72, 44-73, 44-74, 44-75, 44-76, 44-77, 44-78, 4
4-79, 44-80, 44-81, 44-82, 44-83, 44-84, 44-85, 44
-86, 44-87, 44-88, 44-89, 44-90, 44-91, 44-92, 44-
93, 44-94,44-95, 44-96, 44-97,45-1, 45-2, 45-3, 45
-4, 45-5, 45-6, 45-7, 45-8, 45-9, 45-10, 45-11, 45
-12, 45-13, 45-14, 45-15, 45-16, 45-17, 45-18, 45-
19, 45-20, 45-21, 45-22, 45-23, 45-24, 45-25, 45-2
6, 45-27, 45-28, 45-29, 45-30, 45-31, 45-32, 45-3
3, 45-34, 45-35, 45-36, 45-37, 45-38, 45-39, 45-4
0, 45-41, 45-42, 45-43, 45-44, 45-45, 45-46, 45-4
7, 45-48, 45-49, 45-50, 45-51, 45-52, 45-53, 45-5
4, 45-55, 45-56, 45-57, 45-58, 45-59, 45-60, 45-6
1, 45-62, 45-63, 45-64, 45-65, 45-66, 45-67, 45-68,
45-69, 45-70, 45-71, 45-72, 45-73, 45-74, 45-75,
45-76, 45-77, 45-78, 45-79, 45-80, 45-81, 45-82, 4
5-83, 45-84, 45-85, 45-86, 45-87, 45-88, 45-89, 45
-90, 45-91, 45-92, 45-93, 45-94,45-95, 45-96, 45-9
7,46-1, 46-2, 46-3, 46-4, 46-5, 46-6, 46-7, 46-8,
46-9, 46-10, 46-11, 46-12, 46-13, 46-14, 46-15, 46
-16, 46-17, 46-18, 46-19, 46-20, 46-21, 46-22, 46-2
3, 46-24, 46-25, 46-26, 46-27, 46-28, 46-29, 46-3
0, 46-31, 46-32, 46-33, 46-34, 46-35, 46-36, 46-3
7, 46-38, 46-39, 46-40, 46-41, 46-42, 46-43, 46-4
4, 46-45, 46-46, 46-47, 46-48, 46-49, 46-50, 46-5
1, 46-52, 46-53, 46-54, 46-55, 46-56, 46-57, 46-5
8, 46-59, 46-60, 46-61, 46-62, 46-63,46-64, 46-65,
46-66, 46-67, 46-68, 46-69, 46-70, 46-71, 46-72,
46-73, 46-74, 46-75, 46-76, 46-77, 46-78, 46-79, 4
6-80, 46-81, 46-82, 46-83, 46-84, 46-85, 46-86, 46
-87, 46-88, 46-89, 46-90, 46-91, 46-92, 46-93, 46-
94,46-95, 46-96, 46-97,47-1, 47-2, 47-3, 47-4, 47-
5, 47-6, 47-7, 47-8, 47-9, 47-10, 47-11, 47-12, 47
-13, 47-14, 47-15, 47-16, 47-17, 47-18, 47-19, 47-
20, 47-21, 47-22,47-23, 47-24, 47-25, 47-26, 47-2
7, 47-28, 47-29, 47-30, 47-31, 47-32, 47-33, 47-3
4, 47-35, 47-36, 47-37, 47-38, 47-39, 47-40, 47-4
1, 47-42, 47-43, 47-44, 47-45, 47-46, 47-47, 47-4
8, 47-49, 47-50, 47-51, 47-52, 47-53, 47-54, 47-5
5, 47-56, 47-57, 47-58, 47-59, 47-60, 47-61, 47-6
2, 47-63,47-64, 47-65, 47-66, 47-67, 47-68, 47-69,
47-70, 47-71, 47-72, 47-73, 47-74, 47-75, 47-76,
47-77, 47-78, 47-79, 47-80, 47-81, 47-82, 47-83, 4
7-84, 47-85, 47-86, 47-87, 47-88, 47-89, 47-90, 47
-91, 47-92, 47-93, 47-94,47-95, 47-96, 47-97,48-1,
48-2, 48-3, 48-4, 48-5, 48-6, 48-7, 48-8, 48-9, 4
8-10, 48-11, 48-12, 48-13, 48-14, 48-15, 48-16, 48
-17, 48-18, 48-19, 48-20, 48-21, 48-22,48-23, 48-2
4, 48-25, 48-26, 48-27, 48-28, 48-29, 48-30, 48-3
1, 48-32, 48-33, 48-34, 48-35, 48-36, 48-37, 48-3
8, 48-39, 48-40, 48-41, 48-42, 48-43, 48-44, 48-4
5, 48-46, 48-47, 48-48, 48-49, 48-50, 48-51, 48-5
2, 48-53, 48-54, 48-55, 48-56, 48-57, 48-58, 48-5
9, 48-60, 48-61, 48-62, 48-63,48-64, 48-65, 48-66,
48-67, 48-68, 48-69, 48-70, 48-71, 48-72, 48-73,
48-74, 48-75, 48-76, 48-77, 48-78, 48-79, 48-80, 4
8-81, 48-82, 48-83, 48-84, 48-85, 48-86, 48-87, 48
-88, 48-89, 48-90, 48-91, 48-92, 48-93, 48-94,48-9
5, 48-96, 48-97,49-1, 49-2, 49-3, 49-4, 49-5, 49-
6, 49-7, 49-8, 49-9, 49-10, 49-11, 49-12, 49-13, 4
9-14, 49-15, 49-16, 49-17, 49-18, 49-19, 49-20, 49
-21, 49-22, 49-23, 49-24, 49-25, 49-26, 49-27, 49-2
8, 49-29, 49-30, 49-31, 49-32, 49-33, 49-34, 49-3
5, 49-36, 49-37, 49-38, 49-39, 49-40, 49-41, 49-4
2, 49-43, 49-44, 49-45, 49-46, 49-47, 49-48, 49-4
9, 49-50, 49-51, 49-52, 49-53, 49-54, 49-55, 49-5
6, 49-57, 49-58, 49-59, 49-60, 49-61, 49-62, 49-6
3,49-64, 49-65, 49-66, 49-67, 49-68, 49-69, 49-70,
49-71, 49-72, 49-73, 49-74, 49-75, 49-76, 49-77,
49-78, 49-79, 49-80, 49-81, 49-82, 49-83, 49-84, 4
9-85, 49-86, 49-87, 49-88, 49-89, 49-90, 49-91, 49
-92, 49-93, 49-94,49-95, 49-96, 49-97,50-1, 50-2,
50-3, 50-4, 50-5, 50-6, 50-7, 50-8, 50-9, 50-10, 5
0-11, 50-12, 50-13, 50-14, 50-15, 50-16, 50-17, 50
-18, 50-19, 50-20, 50-21, 50-22,50-23, 50-24, 50-2
5, 50-26, 50-27, 50-28, 50-29, 50-30, 50-31, 50-3
2, 50-33, 50-34, 50-35, 50-36, 50-37, 50-38, 50-3
9, 50-40, 50-41, 50-42, 50-43, 50-44, 50-45, 50-4
6, 50-47, 50-48, 50-49, 50-50, 50-51, 50-52, 50-5
3, 50-54, 50-55, 50-56, 50-57, 50-58, 50-59, 50-6
0, 50-61, 50-62, 50-63,50-64, 50-65, 50-66, 50-67,
50-68, 50-69, 50-70, 50-71, 50-72, 50-73, 50-74,
50-75, 50-76, 50-77, 50-78, 50-79, 50-80, 50-81, 5
0-82, 50-83, 50-84, 50-85, 50-86, 50-87, 50-88, 50
-89, 50-90, 50-91, 50-92, 50-93, 50-94,50-95, 50-9
6, 50-97,51-1, 51-2, 51-3, 51-4, 51-5, 51-6, 51-7,
51-8, 51-9, 51-10, 51-11, 51-12, 51-13, 51-14, 51
-15, 51-16, 51-17, 51-18, 51-19, 51-20, 51-21, 51-
22,51-23, 51-24, 51-25, 51-26, 51-27, 51-28, 51-2
9, 51-30, 51-31, 51-32, 51-33, 51-34, 51-35, 51-3
6, 51-37, 51-38, 51-39, 51-40, 51-41, 51-42, 51-4
3, 51-44, 51-45, 51-46, 51-47, 51-48, 51-49, 51-5
0, 51-51, 51-52, 51-53, 51-54, 51-55, 51-56, 51-5
7, 51-58, 51-59, 51-60, 51-61, 51-62, 51-63,51-64,
51-65, 51-66, 51-67, 51-68, 51-69, 51-70, 51-71,
51-72, 51-73, 51-74, 51-75, 51-76, 51-77, 51-78, 5
1-79, 51-80, 51-81, 51-82, 51-83, 51-84, 51-85, 51
-86, 51-87, 51-88, 51-89, 51-90, 51-91, 51-92, 51-
93, 51-94,51-95, 51-96, 51-97,52-1, 52-2, 52-3, 52
-4, 52-5, 52-6, 52-7, 52-8, 52-9, 52-10, 52-11, 52
-12, 52-13, 52-14, 52-15, 52-16, 52-17, 52-18, 52-
19, 52-20, 52-21, 52-22, 52-23, 52-24, 52-25, 52-2
6, 52-27, 52-28, 52-29, 52-30, 52-31, 52-32, 52-3
3, 52-34, 52-35, 52-36, 52-37, 52-38, 52-39, 52-4
0, 52-41, 52-42, 52-43, 52-44, 52-45, 52-46, 52-4
7, 52-48, 52-49, 52-50, 52-51, 52-52, 52-53, 52-5
4, 52-55, 52-56, 52-57, 52-58, 52-59, 52-60, 52-6
1, 52-62, 52-63, 52-64, 52-65, 52-66, 52-67, 52-68,
52-69, 52-70, 52-71, 52-72, 52-73, 52-74, 52-75,
52-76, 52-77, 52-78, 52-79, 52-80, 52-81, 52-82, 5
2-83, 52-84, 52-85, 52-86, 52-87, 52-88, 52-89, 52
-90, 52-91, 52-92, 52-93, 52-94,52-95, 52-96, 52-9
7,53-1, 53-2, 53-3, 53-4, 53-5, 53-6, 53-7, 53-8,
53-9, 53-10, 53-11, 53-12, 53-13, 53-14, 53-15, 53
-16, 53-17, 53-18, 53-19, 53-20, 53-21, 53-22, 53-2
3, 53-24, 53-25, 53-26, 53-27, 53-28, 53-29, 53-3
0, 53-31, 53-32, 53-33, 53-34, 53-35, 53-36, 53-3
7, 53-38, 53-39, 53-40, 53-41, 53-42, 53-43, 53-4
4, 53-45, 53-46, 53-47, 53-48, 53-49, 53-50, 53-5
1, 53-52, 53-53, 53-54, 53-55, 53-56, 53-57, 53-5
8, 53-59, 53-60, 53-61, 53-62, 53-63, 53-64, 53-65,
53-66, 53-67, 53-68, 53-69, 53-70, 53-71, 53-72,
53-73, 53-74, 53-75, 53-76, 53-77, 53-78, 53-79, 5
3-80, 53-81, 53-82, 53-83, 53-84, 53-85, 53-86, 53
-87, 53-88, 53-89, 53-90, 53-91, 53-92, 53-93, 53-
94,53-95, 53-96, 53-97,54-1, 54-2, 54-3, 54-4, 54-
5, 54-6, 54-7, 54-8, 54-9, 54-10, 54-11, 54-12, 54
-13, 54-14, 54-15, 54-16, 54-17, 54-18, 54-19, 54-
20, 54-21, 54-22, 54-23, 54-24, 54-25, 54-26, 54-2
7, 54-28, 54-29, 54-30, 54-31, 54-32, 54-33, 54-3
4, 54-35, 54-36, 54-37, 54-38, 54-39, 54-40, 54-4
1, 54-42, 54-43, 54-44, 54-45, 54-46, 54-47, 54-4
8, 54-49, 54-50, 54-51, 54-52, 54-53, 54-54, 54-5
5, 54-56, 54-57, 54-58, 54-59, 54-60, 54-61, 54-6
2, 54-63, 54-64, 54-65, 54-66, 54-67, 54-68, 54-69,
54-70, 54-71, 54-72, 54-73, 54-74, 54-75, 54-76,
54-77, 54-78, 54-79, 54-80, 54-81, 54-82, 54-83, 5
4-84, 54-85, 54-86, 54-87, 54-88, 54-89, 54-90, 54
-91, 54-92, 54-93, 54-94,54-95, 54-96, 54-97,55-1,
55-2, 55-3, 55-4, 55-5, 55-6, 55-7, 55-8, 55-9, 5
5-10, 55-11, 55-12, 55-13, 55-14, 55-15, 55-16, 55
-17, 55-18, 55-19, 55-20, 55-21, 55-22,55-23, 55-2
4, 55-25, 55-26, 55-27, 55-28, 55-29, 55-30, 55-3
1, 55-32, 55-33, 55-34, 55-35, 55-36, 55-37, 55-3
8, 55-39, 55-40, 55-41, 55-42, 55-43, 55-44, 55-4
5, 55-46, 55-47, 55-48, 55-49, 55-50, 55-51, 55-5
2, 55-53, 55-54, 55-55, 55-56, 55-57, 55-58, 55-5
9, 55-60, 55-61, 55-62, 55-63,55-64, 55-65, 55-66,
55-67, 55-68, 55-69, 55-70, 55-71, 55-72, 55-73,
55-74, 55-75, 55-76, 55-77, 55-78, 55-79, 55-80, 5
5-81, 55-82, 55-83, 55-84, 55-85, 55-86, 55-87, 55
-88, 55-89, 55-90, 55-91, 55-92, 55-93, 55-94,55-9
5, 55-96, 55-97,56-1, 56-2, 56-3, 56-4, 56-5, 56-
6, 56-7, 56-8, 56-9, 56-10, 56-11, 56-12, 56-13, 5
6-14, 56-15, 56-16, 56-17, 56-18, 56-19, 56-20, 56
-21, 56-22, 56-23, 56-24, 56-25, 56-26, 56-27, 56-2
8, 56-29, 56-30, 56-31, 56-32, 56-33, 56-34, 56-3
5, 56-36, 56-37, 56-38, 56-39, 56-40, 56-41, 56-4
2, 56-43, 56-44, 56-45, 56-46, 56-47, 56-48, 56-4
9, 56-50, 56-51, 56-52, 56-53, 56-54, 56-55, 56-5
6, 56-57, 56-58, 56-59, 56-60, 56-61, 56-62, 56-6
3,56-64, 56-65, 56-66, 56-67, 56-68, 56-69, 56-70,
56-71, 56-72, 56-73, 56-74, 56-75, 56-76, 56-77,
56-78, 56-79, 56-80, 56-81, 56-82, 56-83, 56-84, 5
6-85, 56-86, 56-87, 56-88, 56-89, 56-90, 56-91, 56
-92, 56-93, 56-94,56-95, 56-96, 56-97,57-1, 57-2,
57-3, 57-4, 57-5, 57-6, 57-7, 57-8, 57-9, 57-10, 5
7-11, 57-12, 57-13, 57-14, 57-15, 57-16, 57-17, 57
-18, 57-19, 57-20, 57-21, 57-22,57-23, 57-24, 57-2
5, 57-26, 57-27, 57-28, 57-29, 57-30, 57-31, 57-3
2, 57-33, 57-34, 57-35, 57-36, 57-37, 57-38, 57-3
9, 57-40, 57-41, 57-42, 57-43, 57-44, 57-45, 57-4
6, 57-47, 57-48, 57-49, 57-50, 57-51, 57-52, 57-5
3, 57-54, 57-55, 57-56, 57-57, 57-58, 57-59, 57-6
0, 57-61, 57-62, 57-63,57-64, 57-65, 57-66, 57-67,
57-68, 57-69, 57-70, 57-71, 57-72, 57-73, 57-74,
57-75, 57-76, 57-77, 57-78, 57-79, 57-80, 57-81, 5
7-82, 57-83, 57-84, 57-85, 57-86, 57-87, 57-88, 57
-89, 57-90, 57-91, 57-92, 57-93, 57-94,57-95, 57-9
6, 57-97,58-1, 58-2, 58-3, 58-4, 58-5, 58-6, 58-7,
58-8, 58-9, 58-10, 58-11, 58-12, 58-13, 58-14, 58
-15, 58-16, 58-17, 58-18, 58-19, 58-20, 58-21, 58-
22,58-23, 58-24, 58-25, 58-26, 58-27, 58-28, 58-2
9, 58-30, 58-31, 58-32, 58-33, 58-34, 58-35, 58-3
6, 58-37, 58-38, 58-39, 58-40, 58-41, 58-42, 58-4
3, 58-44, 58-45, 58-46, 58-47, 58-48, 58-49, 58-5
0, 58-51, 58-52, 58-53, 58-54, 58-55, 58-56, 58-5
7, 58-58, 58-59, 58-60, 58-61, 58-62, 58-63,58-64,
58-65, 58-66, 58-67, 58-68, 58-69, 58-70, 58-71,
58-72, 58-73, 58-74, 58-75, 58-76, 58-77, 58-78, 5
8-79, 58-80, 58-81, 58-82, 58-83, 58-84, 58-85, 58
-86, 58-87, 58-88, 58-89, 58-90, 58-91, 58-92, 58-
93, 58-94, 58-95, 58-96, 58-97,59-1, 59-2, 59-3, 59
-4, 59-5, 59-6, 59-7, 59-8, 59-9, 59-10, 59-11, 59
-12, 59-13, 59-14, 59-15, 59-16, 59-17, 59-18, 59-
19, 59-20, 59-21, 59-22, 59-23, 59-24, 59-25, 59-2
6, 59-27, 59-28, 59-29, 59-30, 59-31, 59-32, 59-3
3, 59-34, 59-35, 59-36, 59-37, 59-38, 59-39, 59-4
0, 59-41, 59-42, 59-43, 59-44, 59-45, 59-46, 59-4
7, 59-48, 59-49, 59-50, 59-51, 59-52, 59-53, 59-5
4, 59-55, 59-56, 59-57, 59-58, 59-59, 59-60, 59-6
1, 59-62, 59-63,59-64, 59-65, 59-66, 59-67, 59-68,
59-69, 59-70, 59-71, 59-72, 59-73, 59-74, 59-75,
59-76, 59-77, 59-78, 59-79, 59-80, 59-81, 59-82, 5
9-83, 59-84, 59-85, 59-86, 59-87, 59-88, 59-89, 59
-90, 59-91, 59-92, 59-93, 59-94,59-95, 59-96, 59-9
7,60-1, 60-2, 60-3, 60-4, 60-5, 60-6, 60-7, 60-8,
60-9, 60-10, 60-11, 60-12, 60-13, 60-14, 60-15, 60
-16, 60-17, 60-18, 60-19, 60-20, 60-21, 60-22,60-2
3, 60-24, 60-25, 60-26, 60-27, 60-28, 60-29, 60-3
0, 60-31, 60-32, 60-33, 60-34, 60-35, 60-36, 60-3
7, 60-38, 60-39, 60-40, 60-41, 60-42, 60-43, 60-4
4, 60-45, 60-46, 60-47, 60-48, 60-49, 60-50, 60-5
1, 60-52, 60-53, 60-54, 60-55, 60-56, 60-57, 60-5
8, 60-59, 60-60, 60-61, 60-62, 60-63,60-64, 60-65,
60-66, 60-67, 60-68, 60-69, 60-70, 60-71, 60-72,
60-73, 60-74, 60-75, 60-76, 60-77, 60-78, 60-79, 6
0-80, 60-81, 60-82, 60-83, 60-84, 60-85, 60-86, 60
-87, 60-88, 60-89, 60-90, 60-91, 60-92, 60-93, 60-
94,60-95, 60-96, 60-97,61-1, 61-2, 61-3, 61-4, 61-
5, 61-6, 61-7, 61-8, 61-9, 61-10, 61-11, 61-12, 61
-13, 61-14, 61-15, 61-16, 61-17, 61-18, 61-19, 61-
20, 61-21, 61-22, 61-23, 61-24, 61-25, 61-26, 61-2
7, 61-28, 61-29, 61-30, 61-31, 61-32, 61-33, 61-3
4, 61-35, 61-36, 61-37, 61-38, 61-39, 61-40, 61-4
1, 61-42, 61-43, 61-44, 61-45, 61-46, 61-47, 61-4
8, 61-49, 61-50, 61-51, 61-52, 61-53, 61-54, 61-5
5, 61-56, 61-57, 61-58, 61-59, 61-60, 61-61, 61-6
2, 61-63, 61-64, 61-65, 61-66, 61-67, 61-68, 61-69,
61-70, 61-71, 61-72, 61-73, 61-74, 61-75, 61-76,
61-77, 61-78, 61-79, 61-80, 61-81, 61-82, 61-83, 6
1-84, 61-85, 61-86, 61-87, 61-88, 61-89, 61-90, 61
-91, 61-92, 61-93, 61-94,61-95, 61-96, 61-97,62-1,
62-2, 62-3, 62-4, 62-5, 62-6, 62-7, 62-8, 62-9, 6
2-10, 62-11, 62-12, 62-13, 62-14, 62-15, 62-16, 62
-17, 62-18, 62-19, 62-20, 62-21, 62-22, 62-23, 62-2
4, 62-25, 62-26, 62-27, 62-28, 62-29, 62-30, 62-3
1, 62-32, 62-33, 62-34, 62-35, 62-36, 62-37, 62-3
8, 62-39, 62-40, 62-41, 62-42, 62-43, 62-44, 62-4
5, 62-46, 62-47, 62-48, 62-49, 62-50, 62-51, 62-5
2, 62-53, 62-54, 62-55, 62-56, 62-57, 62-58, 62-5
9, 62-60, 62-61, 62-62, 62-63,62-64, 62-65, 62-66,
62-67, 62-68, 62-69, 62-70, 62-71, 62-72, 62-73,
62-74, 62-75, 62-76, 62-77, 62-78, 62-79, 62-80, 6
2-81, 62-82, 62-83, 62-84, 62-85, 62-86, 62-87, 62
-88, 62-89, 62-90, 62-91, 62-92, 62-93, 62-94,62-9
5, 62-96, 62-97,63-1, 63-2, 63-3, 63-4, 63-5, 63-
6, 63-7, 63-8, 63-9, 63-10, 63-11, 63-12, 63-13, 6
3-14, 63-15, 63-16, 63-17, 63-18, 63-19, 63-20, 63
-21, 63-22, 63-23, 63-24, 63-25, 63-26, 63-27, 63-2
8, 63-29, 63-30, 63-31, 63-32, 63-33, 63-34, 63-3
5, 63-36, 63-37, 63-38, 63-39, 63-40, 63-41, 63-4
2, 63-43, 63-44, 63-45, 63-46, 63-47, 63-48, 63-4
9, 63-50, 63-51, 63-52, 63-53, 63-54, 63-55, 63-5
6, 63-57, 63-58, 63-59, 63-60, 63-61, 63-62, 63-6
3,63-64, 63-65, 63-66, 63-67, 63-68, 63-69, 63-70,
63-71, 63-72, 63-73, 63-74, 63-75, 63-76, 63-77,
63-78, 63-79, 63-80, 63-81, 63-82, 63-83, 63-84, 6
3-85, 63-86, 63-87, 63-88, 63-89, 63-90, 63-91, 63
-92, 63-93, 63-94,63-95, 63-96, 63-97,64-1, 64-2,
64-3, 64-4, 64-5, 64-6, 64-7, 64-8, 64-9, 64-10, 6
4-11, 64-12, 64-13, 64-14, 64-15, 64-16, 64-17, 64
-18, 64-19, 64-20, 64-21, 64-22,64-23, 64-24, 64-2
5, 64-26, 64-27, 64-28, 64-29, 64-30, 64-31, 64-3
2, 64-33, 64-34, 64-35, 64-36, 64-37, 64-38, 64-3
9, 64-40, 64-41, 64-42, 64-43, 64-44, 64-45, 64-4
6, 64-47, 64-48, 64-49, 64-50, 64-51, 64-52, 64-5
3, 64-54, 64-55, 64-56, 64-57, 64-58, 64-59, 64-6
0, 64-61, 64-62, 64-63, 64-64, 64-65, 64-66, 64-67,
64-68, 64-69, 64-70, 64-71, 64-72, 64-73, 64-74,
64-75, 64-76, 64-77, 64-78, 64-79, 64-80, 64-81, 6
4-82, 64-83, 64-84, 64-85, 64-86, 64-87, 64-88, 64
-89, 64-90, 64-91, 64-92, 64-93, 64-94, 64-95, 64-9
6, 64-97,65-1, 65-2, 65-3, 65-4, 65-5, 65-6, 65-7,
65-8, 65-9, 65-10, 65-11, 65-12, 65-13, 65-14, 65
-15, 65-16, 65-17, 65-18, 65-19, 65-20, 65-21, 65-
22,65-23, 65-24, 65-25, 65-26, 65-27, 65-28, 65-2
9, 65-30, 65-31, 65-32, 65-33, 65-34, 65-35, 65-3
6, 65-37, 65-38, 65-39, 65-40, 65-41, 65-42, 65-4
3, 65-44, 65-45, 65-46, 65-47, 65-48, 65-49, 65-5
0, 65-51, 65-52, 65-53, 65-54, 65-55, 65-56, 65-5
7, 65-58, 65-59, 65-60, 65-61, 65-62, 65-63,65-64,
65-65, 65-66, 65-67, 65-68, 65-69, 65-70, 65-71,
65-72, 65-73, 65-74, 65-75, 65-76, 65-77, 65-78, 6
5-79, 65-80, 65-81, 65-82, 65-83, 65-84, 65-85, 65
-86, 65-87, 65-88, 65-89, 65-90, 65-91, 65-92, 65-
93, 65-94, 65-95, 65-96, 65-97,66-1, 66-2, 66-3, 66
-4, 66-5, 66-6, 66-7, 66-8, 66-9, 66-10, 66-11, 66
-12, 66-13, 66-14, 66-15, 66-16, 66-17, 66-18, 66-
19, 66-20, 66-21, 66-22, 66-23, 66-24, 66-25, 66-2
6, 66-27, 66-28, 66-29, 66-30, 66-31, 66-32, 66-3
3, 66-34, 66-35, 66-36, 66-37, 66-38, 66-39, 66-4
0, 66-41, 66-42, 66-43, 66-44, 66-45, 66-46, 66-4
7, 66-48, 66-49, 66-50, 66-51, 66-52, 66-53, 66-5
4, 66-55, 66-56, 66-57, 66-58, 66-59, 66-60, 66-6
1, 66-62, 66-63,66-64, 66-65, 66-66, 66-67, 66-68,
66-69, 66-70, 66-71, 66-72, 66-73, 66-74, 66-75,
66-76, 66-77, 66-78, 66-79, 66-80, 66-81, 66-82, 6
6-83, 66-84, 66-85, 66-86, 66-87, 66-88, 66-89, 66
-90, 66-91, 66-92, 66-93, 66-94,66-95, 66-96, 66-9
7,67-1, 67-2, 67-3, 67-4, 67-5, 67-6, 67-7, 67-8,
67-9, 67-10, 67-11, 67-12, 67-13, 67-14, 67-15, 67
-16, 67-17, 67-18, 67-19, 67-20, 67-21, 67-22, 67-2
3, 67-24, 67-25, 67-26, 67-27, 67-28, 67-29, 67-3
0, 67-31, 67-32, 67-33, 67-34, 67-35, 67-36, 67-3
7, 67-38, 67-39, 67-40, 67-41, 67-42, 67-43, 67-4
4, 67-45, 67-46, 67-47, 67-48, 67-49, 67-50, 67-5
1, 67-52, 67-53, 67-54, 67-55, 67-56, 67-57, 67-5
8, 67-59, 67-60, 67-61, 67-62, 67-63, 67-64, 67-65,
67-66, 67-67, 67-68, 67-69, 67-70, 67-71, 67-72,
67-73, 67-74, 67-75, 67-76, 67-77, 67-78, 67-79, 6
7-80, 67-81, 67-82, 67-83, 67-84, 67-85, 67-86, 67
-87, 67-88, 67-89, 67-90, 67-91, 67-92, 67-93, 67-
94,67-95, 67-96, 67-97,68-1, 68-2, 68-3, 68-4, 68-
5, 68-6, 68-7, 68-8, 68-9, 68-10, 68-11, 68-12, 68
-13, 68-14, 68-15, 68-16, 68-17, 68-18, 68-19, 68-
20, 68-21, 68-22,68-23, 68-24, 68-25, 68-26, 68-2
7, 68-28, 68-29, 68-30, 68-31, 68-32, 68-33, 68-3
4, 68-35, 68-36, 68-37, 68-38, 68-39, 68-40, 68-4
1, 68-42, 68-43, 68-44, 68-45, 68-46, 68-47, 68-4
8, 68-49, 68-50, 68-51, 68-52, 68-53, 68-54, 68-5
5, 68-56, 68-57, 68-58, 68-59, 68-60, 68-61, 68-6
2, 68-63,68-64, 68-65, 68-66, 68-67, 68-68, 68-69,
68-70, 68-71, 68-72, 68-73, 68-74, 68-75, 68-76,
68-77, 68-78, 68-79, 68-80, 68-81, 68-82, 68-83, 6
8-84, 68-85, 68-86, 68-87, 68-88, 68-89, 68-90, 68
-91, 68-92, 68-93, 68-94,68-95, 68-96, 68-97,69-1,
69-2, 69-3, 69-4, 69-5, 69-6, 69-7, 69-8, 69-9, 6
9-10, 69-11, 69-12, 69-13, 69-14, 69-15, 69-16, 69
-17, 69-18, 69-19, 69-20, 69-21, 69-22, 69-23, 69-2
4, 69-25, 69-26, 69-27, 69-28, 69-29, 69-30, 69-3
1, 69-32, 69-33, 69-34, 69-35, 69-36, 69-37, 69-3
8, 69-39, 69-40, 69-41, 69-42, 69-43, 69-44, 69-4
5, 69-46, 69-47, 69-48, 69-49, 69-50, 69-51, 69-5
2, 69-53, 69-54, 69-55, 69-56, 69-57, 69-58, 69-5
9, 69-60, 69-61, 69-62, 69-63,69-64, 69-65, 69-66,
69-67, 69-68, 69-69, 69-70, 69-71, 69-72, 69-73,
69-74, 69-75, 69-76, 69-77, 69-78, 69-79, 69-80, 6
9-81, 69-82, 69-83, 69-84, 69-85, 69-86, 69-87, 69
-88, 69-89, 69-90, 69-91, 69-92, 69-93, 69-94,69-9
5, 69-96, 69-97,70-1, 70-2, 70-3, 70-4, 70-5, 70-
6, 70-7, 70-8, 70-9, 70-10, 70-11, 70-12, 70-13, 7
0-14, 70-15, 70-16, 70-17, 70-18, 70-19, 70-20, 70
-21, 70-22, 70-23, 70-24, 70-25, 70-26, 70-27, 70-2
8, 70-29, 70-30, 70-31, 70-32, 70-33, 70-34, 70-3
5, 70-36, 70-37, 70-38, 70-39, 70-40, 70-41, 70-4
2, 70-43, 70-44, 70-45, 70-46, 70-47, 70-48, 70-4
9, 70-50, 70-51, 70-52, 70-53, 70-54, 70-55, 70-5
6, 70-57, 70-58, 70-59, 70-60, 70-61, 70-62, 70-6
3,70-64, 70-65, 70-66, 70-67, 70-68, 70-69, 70-70,
70-71, 70-72, 70-73, 70-74, 70-75, 70-76, 70-77,
70-78, 70-79, 70-80, 70-81, 70-82, 70-83, 70-84, 7
0-85, 70-86, 70-87, 70-88, 70-89, 70-90, 70-91, 70
-92, 70-93, 70-94,70-95, 70-96, 70-97,71-1, 71-2,
71-3, 71-4, 71-5, 71-6, 71-7, 71-8, 71-9, 71-10, 7
1-11, 71-12, 71-13, 71-14, 71-15, 71-16, 71-17, 71
-18, 71-19, 71-20, 71-21, 71-22,71-23, 71-24, 71-2
5, 71-26, 71-27, 71-28, 71-29, 71-30, 71-31, 71-3
2, 71-33, 71-34, 71-35, 71-36, 71-37, 71-38, 71-3
9, 71-40, 71-41, 71-42, 71-43, 71-44, 71-45, 71-4
6, 71-47, 71-48, 71-49, 71-50, 71-51, 71-52, 71-5
3, 71-54, 71-55, 71-56, 71-57, 71-58, 71-59, 71-6
0, 71-61, 71-62, 71-63,71-64, 71-65, 71-66, 71-67,
71-68, 71-69, 71-70, 71-71, 71-72, 71-73, 71-74,
71-75, 71-76, 71-77, 71-78, 71-79, 71-80, 71-81, 7
1-82, 71-83, 71-84, 71-85, 71-86, 71-87, 71-88, 71
-89, 71-90, 71-91, 71-92, 71-93, 71-94,71-95, 71-9
6, 71-97,72-1, 72-2, 72-3, 72-4, 72-5, 72-6, 72-7,
72-8, 72-9, 72-10, 72-11, 72-12, 72-13, 72-14, 72
-15, 72-16, 72-17, 72-18, 72-19, 72-20, 72-21, 72-
22,72-23, 72-24, 72-25, 72-26, 72-27, 72-28, 72-2
9, 72-30, 72-31, 72-32, 72-33, 72-34, 72-35, 72-3
6, 72-37, 72-38, 72-39, 72-40, 72-41, 72-42, 72-4
3, 72-44, 72-45, 72-46, 72-47, 72-48, 72-49, 72-5
0, 72-51, 72-52, 72-53, 72-54, 72-55, 72-56, 72-5
7, 72-58, 72-59, 72-60, 72-61, 72-62, 72-63,72-64,
72-65, 72-66, 72-67, 72-68, 72-69, 72-70, 72-71,
72-72, 72-73, 72-74, 72-75, 72-76, 72-77, 72-78, 7
2-79, 72-80, 72-81, 72-82, 72-83, 72-84, 72-85, 72
-86, 72-87, 72-88, 72-89, 72-90, 72-91, 72-92, 72-
93, 72-94, 72-95, 72-96, 72-97,73-1, 73-2, 73-3, 73
-4, 73-5, 73-6, 73-7, 73-8, 73-9, 73-10, 73-11, 73
-12, 73-13, 73-14, 73-15, 73-16, 73-17, 73-18, 73-
19, 73-20, 73-21, 73-22, 73-23, 73-24, 73-25, 73-2
6, 73-27, 73-28, 73-29, 73-30, 73-31, 73-32, 73-3
3, 73-34, 73-35, 73-36, 73-37, 73-38, 73-39, 73-4
0, 73-41, 73-42, 73-43, 73-44, 73-45, 73-46, 73-4
7, 73-48, 73-49, 73-50, 73-51, 73-52, 73-53, 73-5
4, 73-55, 73-56, 73-57, 73-58, 73-59, 73-60, 73-6
1, 73-62, 73-63, 73-64, 73-65, 73-66, 73-67, 73-68,
73-69, 73-70, 73-71, 73-72, 73-73, 73-74, 73-75,
73-76, 73-77, 73-78, 73-79, 73-80, 73-81, 73-82, 7
3-83, 73-84, 73-85, 73-86, 73-87, 73-88, 73-89, 73
-90, 73-91, 73-92, 73-93, 73-94,73-95, 73-96, 73-9
7,74-1, 74-2, 74-3, 74-4, 74-5, 74-6, 74-7, 74-8,
74-9, 74-10, 74-11, 74-12, 74-13, 74-14, 74-15, 74
-16, 74-17, 74-18, 74-19, 74-20, 74-21, 74-22, 74-2
3, 74-24, 74-25, 74-26, 74-27, 74-28, 74-29, 74-3
0, 74-31, 74-32, 74-33, 74-34, 74-35, 74-36, 74-3
7, 74-38, 74-39, 74-40, 74-41, 74-42, 74-43, 74-4
4, 74-45, 74-46, 74-47, 74-48, 74-49, 74-50, 74-5
1, 74-52, 74-53, 74-54, 74-55, 74-56, 74-57, 74-5
8, 74-59, 74-60, 74-61, 74-62, 74-63, 74-64, 74-65,
74-66, 74-67, 74-68, 74-69, 74-70, 74-71, 74-72,
74-73, 74-74, 74-75, 74-76, 74-77, 74-78, 74-79, 7
4-80, 74-81, 74-82, 74-83, 74-84, 74-85, 74-86, 74
-87, 74-88, 74-89, 74-90, 74-91, 74-92, 74-93, 74-
94,74-95, 74-96, 74-97,75-1, 75-2, 75-3, 75-4, 75-
5, 75-6, 75-7, 75-8, 75-9, 75-10, 75-11, 75-12, 75
-13, 75-14, 75-15, 75-16, 75-17, 75-18, 75-19, 75-
20, 75-21, 75-22, 75-23, 75-24, 75-25, 75-26, 75-2
7, 75-28, 75-29, 75-30, 75-31, 75-32, 75-33, 75-3
4, 75-35, 75-36, 75-37, 75-38, 75-39, 75-40, 75-4
1, 75-42, 75-43, 75-44, 75-45, 75-46, 75-47, 75-4
8, 75-49, 75-50, 75-51, 75-52, 75-53, 75-54, 75-5
5, 75-56, 75-57, 75-58, 75-59, 75-60, 75-61, 75-6
2, 75-63, 75-64, 75-65, 75-66, 75-67, 75-68, 75-69,
75-70, 75-71, 75-72, 75-73, 75-74, 75-75, 75-76,
75-77, 75-78, 75-79, 75-80, 75-81, 75-82, 75-83, 7
5-84, 75-85, 75-86, 75-87, 75-88, 75-89, 75-90, 75
-91, 75-92, 75-93, 75-94,75-95, 75-96, 75-97,76-1,
76-2, 76-3, 76-4, 76-5, 76-6, 76-7, 76-8, 76-9, 7
6-10, 76-11, 76-12, 76-13, 76-14, 76-15, 76-16, 76
-17, 76-18, 76-19, 76-20, 76-21, 76-22,76-23, 76-2
4, 76-25, 76-26, 76-27, 76-28, 76-29, 76-30, 76-3
1, 76-32, 76-33, 76-34, 76-35, 76-36, 76-37, 76-3
8, 76-39, 76-40, 76-41, 76-42, 76-43, 76-44, 76-4
5, 76-46, 76-47, 76-48, 76-49, 76-50, 76-51, 76-5
2, 76-53, 76-54, 76-55, 76-56, 76-57, 76-58, 76-5
9, 76-60, 76-61, 76-62, 76-63,76-64, 76-65, 76-66,
76-67, 76-68, 76-69, 76-70, 76-71, 76-72, 76-73,
76-74, 76-75, 76-76, 76-77, 76-78, 76-79, 76-80, 7
6-81, 76-82, 76-83, 76-84, 76-85, 76-86, 76-87, 76
-88, 76-89, 76-90, 76-91, 76-92, 76-93, 76-94,76-9
5, 76-96, 76-97,77-1, 77-2, 77-3, 77-4, 77-5, 77-
6, 77-7, 77-8, 77-9, 77-10, 77-11, 77-12, 77-13, 7
7-14, 77-15, 77-16, 77-17, 77-18, 77-19, 77-20, 77
-21, 77-22, 77-23, 77-24, 77-25, 77-26, 77-27, 77-2
8, 77-29, 77-30, 77-31, 77-32, 77-33, 77-34, 77-3
5, 77-36, 77-37, 77-38, 77-39, 77-40, 77-41, 77-4
2, 77-43, 77-44, 77-45, 77-46, 77-47, 77-48, 77-4
9, 77-50, 77-51, 77-52, 77-53, 77-54, 77-55, 77-5
6, 77-57, 77-58, 77-59, 77-60, 77-61, 77-62, 77-6
3,77-64, 77-65, 77-66, 77-67, 77-68, 77-69, 77-70,
77-71, 77-72, 77-73, 77-74, 77-75, 77-76, 77-77,
77-78, 77-79, 77-80, 77-81, 77-82, 77-83, 77-84, 7
7-85, 77-86, 77-87, 77-88, 77-89, 77-90, 77-91, 77
-92, 77-93, 77-94,77-95, 77-96, 77-97,78-1, 78-2,
78-3, 78-4, 78-5, 78-6, 78-7, 78-8, 78-9, 78-10, 7
8-11, 78-12, 78-13, 78-14, 78-15, 78-16, 78-17, 78
-18, 78-19, 78-20, 78-21, 78-22,78-23, 78-24, 78-2
5, 78-26, 78-27, 78-28, 78-29, 78-30, 78-31, 78-3
2, 78-33, 78-34, 78-35, 78-36, 78-37, 78-38, 78-3
9, 78-40, 78-41, 78-42, 78-43, 78-44, 78-45, 78-4
6, 78-47, 78-48, 78-49, 78-50, 78-51, 78-52, 78-5
3, 78-54, 78-55, 78-56, 78-57, 78-58, 78-59, 78-6
0, 78-61, 78-62, 78-63, 78-64, 78-65, 78-66, 78-67,
78-68, 78-69, 78-70, 78-71, 78-72, 78-73, 78-74,
78-75, 78-76, 78-77, 78-78, 78-79, 78-80, 78-81, 7
8-82, 78-83, 78-84, 78-85, 78-86, 78-87, 78-88, 78
-89, 78-90, 78-91, 78-92, 78-93, 78-94,78-95, 78-9
6, 78-97,79-1, 79-2, 79-3, 79-4, 79-5, 79-6, 79-7,
79-8, 79-9, 79-10, 79-11, 79-12, 79-13, 79-14, 79
-15, 79-16, 79-17, 79-18, 79-19, 79-20, 79-21, 79-
22,79-23, 79-24, 79-25, 79-26, 79-27, 79-28, 79-2
9, 79-30, 79-31, 79-32, 79-33, 79-34, 79-35, 79-3
6, 79-37, 79-38, 79-39, 79-40, 79-41, 79-42, 79-4
3, 79-44, 79-45, 79-46, 79-47, 79-48, 79-49, 79-5
0, 79-51, 79-52, 79-53, 79-54, 79-55, 79-56, 79-5
7, 79-58, 79-59, 79-60, 79-61, 79-62, 79-63,79-64,
79-65, 79-66, 79-67, 79-68, 79-69, 79-70, 79-71,
79-72, 79-73, 79-74, 79-75, 79-76, 79-77, 79-78, 7
9-79, 79-80, 79-81, 79-82, 79-83, 79-84, 79-85, 79
-86, 79-87, 79-88, 79-89, 79-90, 79-91, 79-92, 79-
93, 79-94, 79-95, 79-96, 79-97,80-1, 80-2, 80-3, 80
-4, 80-5, 80-6, 80-7, 80-8, 80-9, 80-10, 80-11, 80
-12, 80-13, 80-14, 80-15, 80-16, 80-17, 80-18, 80-
19, 80-20, 80-21, 80-22, 80-23, 80-24, 80-25, 80-2
6, 80-27, 80-28, 80-29, 80-30, 80-31, 80-32, 80-3
3, 80-34, 80-35, 80-36, 80-37, 80-38, 80-39, 80-4
0, 80-41, 80-42, 80-43, 80-44, 80-45, 80-46, 80-4
7, 80-48, 80-49, 80-50, 80-51, 80-52, 80-53, 80-5
4, 80-55, 80-56, 80-57, 80-58, 80-59, 80-60, 80-6
1, 80-62, 80-63,80-64, 80-65, 80-66, 80-67, 80-68,
80-69, 80-70, 80-71, 80-72, 80-73, 80-74, 80-75,
80-76, 80-77, 80-78, 80-79, 80-80, 80-81, 80-82, 8
0-83, 80-84, 80-85, 80-86, 80-87, 80-88, 80-89, 80
-90, 80-91, 80-92, 80-93, 80-94,80-95, 80-96, 80-9
7,81-1, 81-2, 81-3, 81-4, 81-5, 81-6, 81-7, 81-8,
81-9, 81-10, 81-11, 81-12, 81-13, 81-14, 81-15, 81
-16, 81-17, 81-18, 81-19, 81-20, 81-21, 81-22,81-2
3, 81-24, 81-25, 81-26, 81-27, 81-28, 81-29, 81-3
0, 81-31, 81-32, 81-33, 81-34, 81-35, 81-36, 81-3
7, 81-38, 81-39, 81-40, 81-41, 81-42, 81-43, 81-4
4, 81-45, 81-46, 81-47, 81-48, 81-49, 81-50, 81-5
1, 81-52, 81-53, 81-54, 81-55, 81-56, 81-57, 81-5
8, 81-59, 81-60, 81-61, 81-62, 81-63,81-64, 81-65,
81-66, 81-67, 81-68, 81-69, 81-70, 81-71, 81-72,
81-73, 81-74, 81-75, 81-76, 81-77, 81-78, 81-79, 8
1-80, 81-81, 81-82, 81-83, 81-84, 81-85, 81-86, 81
-87, 81-88, 81-89, 81-90, 81-91, 81-92, 81-93, 81-
94,81-95, 81-96, 81-97,82-1, 82-2, 82-3, 82-4, 82-
5, 82-6, 82-7, 82-8, 82-9, 82-10, 82-11, 82-12, 82
-13, 82-14, 82-15, 82-16, 82-17, 82-18, 82-19, 82-
20, 82-21, 82-22, 82-23, 82-24, 82-25, 82-26, 82-2
7, 82-28, 82-29, 82-30, 82-31, 82-32, 82-33, 82-3
4, 82-35, 82-36, 82-37, 82-38, 82-39, 82-40, 82-4
1, 82-42, 82-43, 82-44, 82-45, 82-46, 82-47, 82-4
8, 82-49, 82-50, 82-51, 82-52, 82-53, 82-54, 82-5
5, 82-56, 82-57, 82-58, 82-59, 82-60, 82-61, 82-6
2, 82-63, 82-64, 82-65, 82-66, 82-67, 82-68, 82-69,
82-70, 82-71, 82-72, 82-73, 82-74, 82-75, 82-76,
82-77, 82-78, 82-79, 82-80, 82-81, 82-82, 82-83, 8
2-84, 82-85, 82-86, 82-87, 82-88, 82-89, 82-90, 82
-91, 82-92, 82-93, 82-94,82-95, 82-96, 82-97,83-1,
83-2, 83-3, 83-4, 83-5, 83-6, 83-7, 83-8, 83-9, 8
3-10, 83-11, 83-12, 83-13, 83-14, 83-15, 83-16, 83
-17, 83-18, 83-19, 83-20, 83-21, 83-22,83-23, 83-2
4, 83-25, 83-26, 83-27, 83-28, 83-29, 83-30, 83-3
1, 83-32, 83-33, 83-34, 83-35, 83-36, 83-37, 83-3
8, 83-39, 83-40, 83-41, 83-42, 83-43, 83-44, 83-4
5, 83-46, 83-47, 83-48, 83-49, 83-50, 83-51, 83-5
2, 83-53, 83-54, 83-55, 83-56, 83-57, 83-58, 83-5
9, 83-60, 83-61, 83-62, 83-63,83-64, 83-65, 83-66,
83-67, 83-68, 83-69, 83-70, 83-71, 83-72, 83-73,
83-74, 83-75, 83-76, 83-77, 83-78, 83-79, 83-80, 8
3-81, 83-82, 83-83, 83-84, 83-85, 83-86, 83-87, 83
-88, 83-89, 83-90, 83-91, 83-92, 83-93, 83-94,83-9
5, 83-96, 83-97,84-1, 84-2, 84-3, 84-4, 84-5, 84-
6, 84-7, 84-8, 84-9, 84-10, 84-11, 84-12, 84-13, 8
4-14, 84-15, 84-16, 84-17, 84-18, 84-19, 84-20, 84
-21, 84-22, 84-23, 84-24, 84-25, 84-26, 84-27, 84-2
8, 84-29, 84-30, 84-31, 84-32, 84-33, 84-34, 84-3
5, 84-36, 84-37, 84-38, 84-39, 84-40, 84-41, 84-4
2, 84-43, 84-44, 84-45, 84-46, 84-47, 84-48, 84-4
9, 84-50, 84-51, 84-52, 84-53, 84-54, 84-55, 84-5
6, 84-57, 84-58, 84-59, 84-60, 84-61, 84-62, 84-6
3,84-64, 84-65, 84-66, 84-67, 84-68, 84-69, 84-70,
84-71, 84-72, 84-73, 84-74, 84-75, 84-76, 84-77,
84-78, 84-79, 84-80, 84-81, 84-82, 84-83, 84-84, 8
4-85, 84-86, 84-87, 84-88, 84-89, 84-90, 84-91, 84
-92, 84-93, 84-94,84-95, 84-96, 84-97,85-1, 85-2,
85-3, 85-4, 85-5, 85-6, 85-7, 85-8, 85-9, 85-10, 8
5-11, 85-12, 85-13, 85-14, 85-15, 85-16, 85-17, 85
-18, 85-19, 85-20, 85-21, 85-22,85-23, 85-24, 85-2
5, 85-26, 85-27, 85-28, 85-29, 85-30, 85-31, 85-3
2, 85-33, 85-34, 85-35, 85-36, 85-37, 85-38, 85-3
9, 85-40, 85-41, 85-42, 85-43, 85-44, 85-45, 85-4
6, 85-47, 85-48, 85-49, 85-50, 85-51, 85-52, 85-5
3, 85-54, 85-55, 85-56, 85-57, 85-58, 85-59, 85-6
0, 85-61, 85-62, 85-63,85-64, 85-65, 85-66, 85-67,
85-68, 85-69, 85-70, 85-71, 85-72, 85-73, 85-74,
85-75, 85-76, 85-77, 85-78, 85-79, 85-80, 85-81, 8
5-82, 85-83, 85-84, 85-85, 85-86, 85-87, 85-88, 85
-89, 85-90, 85-91, 85-92, 85-93, 85-94,85-95, 85-9
6, 85-97,86-1, 86-2, 86-3, 86-4, 86-5, 86-6, 86-7,
86-8, 86-9, 86-10, 86-11, 86-12, 86-13, 86-14, 86
-15, 86-16, 86-17, 86-18, 86-19, 86-20, 86-21, 86-
22,86-23, 86-24, 86-25, 86-26, 86-27, 86-28, 86-2
9, 86-30, 86-31, 86-32, 86-33, 86-34, 86-35, 86-3
6, 86-37, 86-38, 86-39, 86-40, 86-41, 86-42, 86-4
3, 86-44, 86-45, 86-46, 86-47, 86-48, 86-49, 86-5
0, 86-51, 86-52, 86-53, 86-54, 86-55, 86-56, 86-5
7, 86-58, 86-59, 86-60, 86-61, 86-62, 86-63,86-64,
86-65, 86-66, 86-67, 86-68, 86-69, 86-70, 86-71,
86-72, 86-73, 86-74, 86-75, 86-76, 86-77, 86-78, 8
6-79, 86-80, 86-81, 86-82, 86-83, 86-84, 86-85, 86
-86, 86-87, 86-88, 86-89, 86-90, 86-91, 86-92, 86-
93, 86-94,86-95, 86-96, 86-97,87-1, 87-2, 87-3, 87
-4, 87-5, 87-6, 87-7, 87-8, 87-9, 87-10, 87-11, 87
-12, 87-13, 87-14, 87-15, 87-16, 87-17, 87-18, 87-
19, 87-20, 87-21, 87-22,87-23, 87-24, 87-25, 87-2
6, 87-27, 87-28, 87-29, 87-30, 87-31, 87-32, 87-3
3, 87-34, 87-35, 87-36, 87-37, 87-38, 87-39, 87-4
0, 87-41, 87-42, 87-43, 87-44, 87-45, 87-46, 87-4
7, 87-48, 87-49, 87-50, 87-51, 87-52, 87-53, 87-5
4, 87-55, 87-56, 87-57, 87-58, 87-59, 87-60, 87-6
1, 87-62, 87-63,87-64, 87-65, 87-66, 87-67, 87-68,
87-69, 87-70, 87-71, 87-72, 87-73, 87-74, 87-75,
87-76, 87-77, 87-78, 87-79, 87-80, 87-81, 87-82, 8
7-83, 87-84, 87-85, 87-86, 87-87, 87-88, 87-89, 87
-90, 87-91, 87-92, 87-93, 87-94,87-95, 87-96, 87-9
7,88-1, 88-2, 88-3, 88-4, 88-5, 88-6, 88-7, 88-8,
88-9, 88-10, 88-11, 88-12, 88-13, 88-14, 88-15, 88
-16, 88-17, 88-18, 88-19, 88-20, 88-21, 88-22,88-2
3, 88-24, 88-25, 88-26, 88-27, 88-28, 88-29, 88-3
0, 88-31, 88-32, 88-33, 88-34, 88-35, 88-36, 88-3
7, 88-38, 88-39, 88-40, 88-41, 88-42, 88-43, 88-4
4, 88-45, 88-46, 88-47, 88-48, 88-49, 88-50, 88-5
1, 88-52, 88-53, 88-54, 88-55, 88-56, 88-57, 88-5
8, 88-59, 88-60, 88-61, 88-62, 88-63,88-64, 88-65,
88-66, 88-67, 88-68, 88-69, 88-70, 88-71, 88-72,
88-73, 88-74, 88-75, 88-76, 88-77, 88-78, 88-79, 8
8-80, 88-81, 88-82, 88-83, 88-84, 88-85, 88-86, 88
-87, 88-88, 88-89, 88-90, 88-91, 88-92, 88-93, 88-
94,88-95, 88-96, 88-97,89-1, 89-2, 89-3, 89-4, 89-
5, 89-6, 89-7, 89-8, 89-9, 89-10, 89-11, 89-12, 89
-13, 89-14, 89-15, 89-16, 89-17, 89-18, 89-19, 89-
20, 89-21, 89-22,89-23, 89-24, 89-25, 89-26, 89-2
7, 89-28, 89-29, 89-30, 89-31, 89-32, 89-33, 89-3
4, 89-35, 89-36, 89-37, 89-38, 89-39, 89-40, 89-4
1, 89-42, 89-43, 89-44, 89-45, 89-46, 89-47, 89-4
8, 89-49, 89-50, 89-51, 89-52, 89-53, 89-54, 89-5
5, 89-56, 89-57, 89-58, 89-59, 89-60, 89-61, 89-6
2, 89-63,89-64, 89-65, 89-66, 89-67, 89-68, 89-69,
89-70, 89-71, 89-72, 89-73, 89-74, 89-75, 89-76,
89-77, 89-78, 89-79, 89-80, 89-81, 89-82, 89-83, 8
9-84, 89-85, 89-86, 89-87, 89-88, 89-89, 89-90, 89
-91, 89-92, 89-93, 89-94,89-95, 89-96, 89-97,90-1,
90-2, 90-3, 90-4, 90-5, 90-6, 90-7, 90-8, 90-9, 9
0-10, 90-11, 90-12, 90-13, 90-14, 90-15, 90-16, 90
-17, 90-18, 90-19, 90-20, 90-21, 90-22,90-23, 90-2
4, 90-25, 90-26, 90-27, 90-28, 90-29, 90-30, 90-3
1, 90-32, 90-33, 90-34, 90-35, 90-36, 90-37, 90-3
8, 90-39, 90-40, 90-41, 90-42, 90-43, 90-44, 90-4
5, 90-46, 90-47, 90-48, 90-49, 90-50, 90-51, 90-5
2, 90-53, 90-54, 90-55, 90-56, 90-57, 90-58, 90-5
9, 90-60, 90-61, 90-62, 90-63,90-64, 90-65, 90-66,
90-67, 90-68, 90-69, 90-70, 90-71, 90-72, 90-73,
90-74, 90-75, 90-76, 90-77, 90-78, 90-79, 90-80, 9
0-81, 90-82, 90-83, 90-84, 90-85, 90-86, 90-87, 90
-88, 90-89, 90-90, 90-91, 90-92, 90-93, 90-94,90-9
5, 90-96, 90-97,91-1, 91-2, 91-3, 91-4, 91-5, 91-
6, 91-7, 91-8, 91-9, 91-10, 91-11, 91-12, 91-13, 9
1-14, 91-15, 91-16, 91-17, 91-18, 91-19, 91-20, 91
-21, 91-22, 91-23, 91-24, 91-25, 91-26, 91-27, 91-2
8, 91-29, 91-30, 91-31, 91-32, 91-33, 91-34, 91-3
5, 91-36, 91-37, 91-38, 91-39, 91-40, 91-41, 91-4
2, 91-43, 91-44, 91-45, 91-46, 91-47, 91-48, 91-4
9, 91-50, 91-51, 91-52, 91-53, 91-54, 91-55, 91-5
6, 91-57, 91-58, 91-59, 91-60, 91-61, 91-62, 91-6
3,91-64, 91-65, 91-66, 91-67, 91-68, 91-69, 91-70,
91-71, 91-72, 91-73, 91-74, 91-75, 91-76, 91-77,
91-78, 91-79, 91-80, 91-81, 91-82, 91-83, 91-84, 9
1-85, 91-86, 91-87, 91-88, 91-89, 91-90, 91-91, 91
-92, 91-93, 91-94,91-95, 91-96, 91-97,92-1, 92-2,
92-3, 92-4, 92-5, 92-6, 92-7, 92-8, 92-9, 92-10, 9
2-11, 92-12, 92-13, 92-14, 92-15, 92-16, 92-17, 92
-18, 92-19, 92-20, 92-21, 92-22,92-23, 92-24, 92-2
5, 92-26, 92-27, 92-28, 92-29, 92-30, 92-31, 92-3
2, 92-33, 92-34, 92-35, 92-36, 92-37, 92-38, 92-3
9, 92-40, 92-41, 92-42, 92-43, 92-44, 92-45, 92-4
6, 92-47, 92-48, 92-49, 92-50, 92-51, 92-52, 92-5
3, 92-54, 92-55, 92-56, 92-57, 92-58, 92-59, 92-6
0, 92-61, 92-62, 92-63,92-64, 92-65, 92-66, 92-67,
92-68, 92-69, 92-70, 92-71, 92-72, 92-73, 92-74,
92-75, 92-76, 92-77, 92-78, 92-79, 92-80, 92-81, 9
2-82, 92-83, 92-84, 92-85, 92-86, 92-87, 92-88, 92
-89, 92-90, 92-91, 92-92, 92-93, 92-94,92-95, 92-9
6, 92-97,93-1, 93-2, 93-3, 93-4, 93-5, 93-6, 93-7,
93-8, 93-9, 93-10, 93-11, 93-12, 93-13, 93-14, 93
-15, 93-16, 93-17, 93-18, 93-19, 93-20, 93-21, 93-
22,93-23, 93-24, 93-25, 93-26, 93-27, 93-28, 93-2
9, 93-30, 93-31, 93-32, 93-33, 93-34, 93-35, 93-3
6, 93-37, 93-38, 93-39, 93-40, 93-41, 93-42, 93-4
3, 93-44, 93-45, 93-46, 93-47, 93-48, 93-49, 93-5
0, 93-51, 93-52, 93-53, 93-54, 93-55, 93-56, 93-5
7, 93-58, 93-59, 93-60, 93-61, 93-62, 93-63,93-64,
93-65, 93-66, 93-67, 93-68, 93-69, 93-70, 93-71,
93-72, 93-73, 93-74, 93-75, 93-76, 93-77, 93-78, 9
3-79, 93-80, 93-81, 93-82, 93-83, 93-84, 93-85, 93
-86, 93-87, 93-88, 93-89, 93-90, 93-91, 93-92, 93-
93, 93-94,93-95, 93-96, 93-97,94-1, 94-2, 94-3, 94
-4, 94-5, 94-6, 94-7, 94-8, 94-9, 94-10, 94-11, 94
-12, 94-13, 94-14, 94-15, 94-16, 94-17, 94-18, 94-
19, 94-20, 94-21, 94-22, 94-23, 94-24, 94-25, 94-2
6, 94-27, 94-28, 94-29, 94-30, 94-31, 94-32, 94-3
3, 94-34, 94-35, 94-36, 94-37, 94-38, 94-39, 94-4
0, 94-41, 94-42, 94-43, 94-44, 94-45, 94-46, 94-4
7, 94-48, 94-49, 94-50, 94-51, 94-52, 94-53, 94-5
4, 94-55, 94-56, 94-57, 94-58, 94-59, 94-60, 94-6
1, 94-62, 94-63,94-64, 94-65, 94-66, 94-67, 94-68,
94-69, 94-70, 94-71, 94-72, 94-73, 94-74, 94-75,
94-76, 94-77, 94-78, 94-79, 94-80, 94-81, 94-82, 9
4-83, 94-84, 94-85, 94-86, 94-87, 94-88, 94-89, 94
-90, 94-91, 94-92, 94-93, 94-94,94-95, 94-96, 94-9
7,95-1, 95-2, 95-3, 95-4, 95-5, 95-6, 95-7, 95-8,
95-9, 95-10, 95-11, 95-12, 95-13, 95-14, 95-15, 95
-16, 95-17, 95-18, 95-19, 95-20, 95-21, 95-22,95-2
3, 95-24, 95-25, 95-26, 95-27, 95-28, 95-29, 95-3
0, 95-31, 95-32, 95-33, 95-34, 95-35, 95-36, 95-3
7, 95-38, 95-39, 95-40, 95-41, 95-42, 95-43, 95-4
4, 95-45, 95-46, 95-47, 95-48, 95-49, 95-50, 95-5
1, 95-52, 95-53, 95-54, 95-55, 95-56, 95-57, 95-5
8, 95-59, 95-60, 95-61, 95-62, 95-63,95-64, 95-65,
95-66, 95-67, 95-68, 95-69, 95-70, 95-71, 95-72,
95-73, 95-74, 95-75, 95-76, 95-77, 95-78, 95-79, 9
5-80, 95-81, 95-82, 95-83, 95-84, 95-85, 95-86, 95
-87, 95-88, 95-89, 95-90, 95-91, 95-92, 95-93, 95-
94,95-95, 95-96, 95-97,96-1, 96-2, 96-3, 96-4, 96-
5, 96-6, 96-7, 96-8, 96-9, 96-10, 96-11, 96-12, 96
-13, 96-14, 96-15, 96-16, 96-17, 96-18, 96-19, 96-
20, 96-21, 96-22, 96-23, 96-24, 96-25, 96-26, 96-2
7, 96-28, 96-29, 96-30, 96-31, 96-32, 96-33, 96-3
4, 96-35, 96-36, 96-37, 96-38, 96-39, 96-40, 96-4
1, 96-42, 96-43, 96-44, 96-45, 96-46, 96-47, 96-4
8, 96-49, 96-50, 96-51, 96-52, 96-53, 96-54, 96-5
5, 96-56, 96-57, 96-58, 96-59, 96-60, 96-61, 96-6
2, 96-63, 96-64, 96-65, 96-66, 96-67, 96-68, 96-69,
96-70, 96-71, 96-72, 96-73, 96-74, 96-75, 96-76,
96-77, 96-78, 96-79, 96-80, 96-81, 96-82, 96-83, 9
6-84, 96-85, 96-86, 96-87, 96-88, 96-89, 96-90, 96
-91, 96-92, 96-93, 96-94,96-95, 96-96, 96-97,97-1,
97-2, 97-3, 97-4, 97-5, 97-6, 97-7, 97-8, 97-9, 9
7-10, 97-11, 97-12, 97-13, 97-14, 97-15, 97-16, 97
-17, 97-18, 97-19, 97-20, 97-21, 97-22,97-23, 97-2
4, 97-25, 97-26, 97-27, 97-28, 97-29, 97-30, 97-3
1, 97-32, 97-33, 97-34, 97-35, 97-36, 97-37, 97-3
8, 97-39, 97-40, 97-41, 97-42, 97-43, 97-44, 97-4
5, 97-46, 97-47, 97-48, 97-49, 97-50, 97-51, 97-5
2, 97-53, 97-54, 97-55, 97-56, 97-57, 97-58, 97-5
9, 97-60, 97-61, 97-62, 97-63,97-64, 97-65, 97-66,
97-67, 97-68, 97-69, 97-70, 97-71, 97-72, 97-73,
97-74, 97-75, 97-76, 97-77, 97-78, 97-79, 97-80, 9
7-81, 97-82, 97-83, 97-84, 97-85, 97-86, 97-87, 97
-88, 97-89, 97-90, 97-91, 97-92, 97-93, 97-94,97-9
5, 97-96, 97-97,98-1, 98-2, 98-3, 98-4, 98-5, 98-
6, 98-7, 98-8, 98-9, 98-10, 98-11, 98-12, 98-13, 9
8-14, 98-15, 98-16, 98-17, 98-18, 98-19, 98-20, 98
-21, 98-22, 98-23, 98-24, 98-25, 98-26, 98-27, 98-2
8, 98-29, 98-30, 98-31, 98-32, 98-33, 98-34, 98-3
5, 98-36, 98-37, 98-38, 98-39, 98-40, 98-41, 98-4
2, 98-43, 98-44, 98-45, 98-46, 98-47, 98-48, 98-4
9, 98-50, 98-51, 98-52, 98-53, 98-54, 98-55, 98-5
6, 98-57, 98-58, 98-59, 98-60, 98-61, 98-62, 98-6
3,98-64, 98-65, 98-66, 98-67, 98-68, 98-69, 98-70,
98-71, 98-72, 98-73, 98-74, 98-75, 98-76, 98-77,
98-78, 98-79, 98-80, 98-81, 98-82, 98-83, 98-84, 9
8-85, 98-86, 98-87, 98-88, 98-89, 98-90, 98-91, 98
-92, 98-93, 98-94,98-95, 98-96, 98-97,99-1, 99-2,
99-3, 99-4, 99-5, 99-6, 99-7, 99-8, 99-9, 99-10, 9
9-11, 99-12, 99-13, 99-14, 99-15, 99-16, 99-17, 99
-18, 99-19, 99-20, 99-21, 99-22,99-23, 99-24, 99-2
5, 99-26, 99-27, 99-28, 99-29, 99-30, 99-31, 99-3
2, 99-33, 99-34, 99-35, 99-36, 99-37, 99-38, 99-3
9, 99-40, 99-41, 99-42, 99-43, 99-44, 99-45, 99-4
6, 99-47, 99-48, 99-49, 99-50, 99-51, 99-52, 99-5
3, 99-54, 99-55, 99-56, 99-57, 99-58, 99-59, 99-6
0, 99-61, 99-62, 99-63,99-64, 99-65, 99-66, 99-67,
99-68, 99-69, 99-70, 99-71, 99-72, 99-73, 99-74,
99-75, 99-76, 99-77, 99-78, 99-79, 99-80, 99-81, 9
9-82, 99-83, 99-84, 99-85, 99-86, 99-87, 99-88, 99
-89, 99-90, 99-91, 99-92, 99-93, 99-94,99-95, 99-9
6, 99-97,100-1, 100-2, 100-3, 100-4, 100-5, 100-6,
100-7, 100-8, 100-9, 100-10, 100-11, 100-12, 100-
13, 100-14, 100-15, 100-16, 100-17, 100-18, 100-1
9, 100-20, 100-21, 100-22, 100-23, 100-24, 100-25,
100-26, 100-27, 100-28, 100-29, 100-30, 100-31, 1
00-32, 100-33, 100-34, 100-35, 100-36, 100-37, 100
-38, 100-39, 100-40, 100-41, 100-42, 100-43, 100-4
4, 100-45, 100-46, 100-47, 100-48, 100-49, 100-50,
100-51, 100-52, 100-53, 100-54, 100-55, 100-56, 1
00-57, 100-58, 100-59, 100-60, 100-61, 100-62, 100
-63, 100-64, 100-65, 100-66, 100-67, 100-68, 100-6
9, 100-70, 100-71, 100-72, 100-73, 100-74, 100-75,
100-76, 100-77, 100-78, 100-79, 100-80, 100-81, 1
00-82, 100-83, 100-84, 100-85, 100-86, 100-87, 100
-88, 100-89, 100-90, 100-91, 100-92, 100-93, 100-9
4, 100-95, 100-96, 100-97,101-1, 101-2, 101-3, 101
-4, 101-5, 101-6, 101-7, 101-8, 101-9, 101-10, 101
-11, 101-12, 101-13, 101-14, 101-15, 101-16, 101-1
7, 101-18, 101-19, 101-20, 101-21, 101-22, 101-23,
101-24, 101-25, 101-26, 101-27, 101-28, 101-29, 1
01-30, 101-31, 101-32, 101-33, 101-34, 101-35, 101
-36, 101-37, 101-38, 101-39, 101-40, 101-41, 101-4
2, 101-43, 101-44, 101-45, 101-46, 101-47, 101-48,
101-49, 101-50, 101-51, 101-52, 101-53, 101-54, 1
01-55, 101-56, 101-57, 101-58, 101-59, 101-60, 101
-61, 101-62, 101-63, 101-64, 101-65, 101-66, 101-6
7, 101-68, 101-69, 101-70, 101-71, 101-72, 101-73,
101-74, 101-75, 101-76, 101-77, 101-78, 101-79, 1
01-80, 101-81, 101-82, 101-83, 101-84, 101-85, 101
-86, 101-87, 101-88, 101-89, 101-90, 101-91, 101-9
2, 101-93, 101-94, 101-95, 101-96, 101-97,102-1, 1
02-2, 102-3, 102-4, 102-5, 102-6, 102-7, 102-8, 10
2-9, 102-10, 102-11, 102-12, 102-13, 102-14, 102-1
5, 102-16, 102-17, 102-18, 102-19, 102-20, 102-21,
102-22, 102-23, 102-24, 102-25, 102-26, 102-27, 1
02-28, 102-29, 102-30, 102-31, 102-32, 102-33, 102
-34, 102-35, 102-36, 102-37, 102-38, 102-39, 102-4
0, 102-41, 102-42, 102-43, 102-44, 102-45, 102-46,
102-47, 102-48, 102-49, 102-50, 102-51, 102-52, 1
02-53, 102-54, 102-55, 102-56, 102-57, 102-58, 102
-59, 102-60, 102-61, 102-62, 102-63, 102-64, 102-6
5, 102-66, 102-67, 102-68, 102-69, 102-70, 102-71,
102-72, 102-73, 102-74, 102-75, 102-76, 102-77, 1
02-78, 102-79, 102-80, 102-81, 102-82, 102-83, 102
-84, 102-85, 102-86, 102-87, 102-88, 102-89, 102-9
0, 102-91, 102-92, 102-93, 102-94, 102-95, 102-96,
102-97,103-1, 103-2, 103-3, 103-4, 103-5, 103-6,
103-7, 103-8, 103-9, 103-10, 103-11, 103-12, 103-1
3, 103-14, 103-15, 103-16, 103-17, 103-18, 103-19,
103-20, 103-21, 103-22, 103-23, 103-24, 103-25, 1
03-26, 103-27, 103-28, 103-29, 103-30, 103-31, 103
-32, 103-33, 103-34, 103-35, 103-36, 103-37, 103-3
8, 103-39, 103-40, 103-41, 103-42, 103-43, 103-44,
103-45, 103-46, 103-47, 103-48, 103-49, 103-50, 1
03-51, 103-52, 103-53, 103-54, 103-55, 103-56, 103
-57, 103-58, 103-59, 103-60, 103-61, 103-62, 103-6
3, 103-64, 103-65, 103-66, 103-67, 103-68, 103-69,
103-70, 103-71, 103-72, 103-73, 103-74, 103-75, 1
03-76, 103-77, 103-78, 103-79, 103-80, 103-81, 103
-82, 103-83, 103-84, 103-85, 103-86, 103-87, 103-8
8, 103-89, 103-90, 103-91, 103-92, 103-93, 103-94,
103-95, 103-96, 103-97,104-1, 104-2, 104-3, 104-
4, 104-5, 104-6, 104-7, 104-8, 104-9, 104-10, 104-
11, 104-12, 104-13, 104-14, 104-15, 104-16, 104-1
7, 104-18, 104-19, 104-20, 104-21, 104-22, 104-23,
104-24, 104-25, 104-26, 104-27, 104-28, 104-29, 1
04-30, 104-31, 104-32, 104-33, 104-34, 104-35, 104
-36, 104-37, 104-38, 104-39, 104-40, 104-41, 104-4
2, 104-43, 104-44, 104-45, 104-46, 104-47, 104-48,
104-49, 104-50, 104-51, 104-52, 104-53, 104-54, 1
04-55, 104-56, 104-57, 104-58, 104-59, 104-60, 104
-61, 104-62, 104-63, 104-64, 104-65, 104-66, 104-6
7, 104-68, 104-69, 104-70, 104-71, 104-72, 104-73,
104-74, 104-75, 104-76, 104-77, 104-78, 104-79, 1
04-80, 104-81, 104-82, 104-83, 104-84, 104-85, 104
-86, 104-87, 104-88, 104-89, 104-90, 104-91, 104-9
2, 104-93, 104-94, 104-95, 104-96, 104-97,105-1, 1
05-2, 105-3, 105-4, 105-5, 105-6, 105-7, 105-8, 10
5-9, 105-10, 105-11, 105-12, 105-13, 105-14, 105-1
5, 105-16, 105-17, 105-18, 105-19, 105-20, 105-21,
105-22, 105-23, 105-24, 105-25, 105-26, 105-27, 1
05-28, 105-29, 105-30, 105-31, 105-32, 105-33, 105
-34, 105-35, 105-36, 105-37, 105-38, 105-39, 105-4
0, 105-41, 105-42, 105-43, 105-44, 105-45, 105-46,
105-47, 105-48, 105-49, 105-50, 105-51, 105-52, 1
05-53, 105-54, 105-55, 105-56, 105-57, 105-58, 105
-59, 105-60, 105-61, 105-62, 105-63, 105-64, 105-6
5, 105-66, 105-67, 105-68, 105-69, 105-70, 105-71,
105-72, 105-73, 105-74, 105-75, 105-76, 105-77, 1
05-78, 105-79, 105-80, 105-81, 105-82, 105-83, 105
-84, 105-85, 105-86, 105-87, 105-88, 105-89, 105-9
0, 105-91, 105-92, 105-93, 105-94, 105-95, 105-96,
105-97,106-1, 106-2, 106-3, 106-4, 106-5, 106-6,
106-7, 106-8, 106-9, 106-10, 106-11, 106-12, 106-1
3, 106-14, 106-15, 106-16, 106-17, 106-18, 106-19,
106-20, 106-21, 106-22, 106-23, 106-24, 106-25, 1
06-26, 106-27, 106-28, 106-29, 106-30, 106-31, 106
-32, 106-33, 106-34, 106-35, 106-36, 106-37, 106-3
8, 106-39, 106-40, 106-41, 106-42, 106-43, 106-44,
106-45, 106-46, 106-47, 106-48, 106-49, 106-50, 1
06-51, 106-52, 106-53, 106-54, 106-55, 106-56, 106
-57, 106-58, 106-59, 106-60, 106-61, 106-62, 106-6
3, 106-64, 106-65, 106-66, 106-67, 106-68, 106-69,
106-70, 106-71, 106-72, 106-73, 106-74, 106-75, 1
06-76, 106-77, 106-78, 106-79, 106-80, 106-81, 106
-82, 106-83, 106-84, 106-85, 106-86, 106-87, 106-8
8, 106-89, 106-90, 106-91, 106-92, 106-93, 106-94,
106-95, 106-96, 106-97,107-1, 107-2, 107-3, 107-
4, 107-5, 107-6, 107-7, 107-8, 107-9, 107-10, 107-
11, 107-12, 107-13, 107-14, 107-15, 107-16, 107-1
7, 107-18, 107-19, 107-20, 107-21, 107-22, 107-23,
107-24, 107-25, 107-26, 107-27, 107-28, 107-29, 1
07-30, 107-31, 107-32, 107-33, 107-34, 107-35, 107
-36, 107-37, 107-38, 107-39, 107-40, 107-41, 107-4
2, 107-43, 107-44, 107-45, 107-46, 107-47, 107-48,
107-49, 107-50, 107-51, 107-52, 107-53, 107-54, 1
07-55, 107-56, 107-57, 107-58, 107-59, 107-60, 107
-61, 107-62, 107-63, 107-64, 107-65, 107-66, 107-6
7, 107-68, 107-69, 107-70, 107-71, 107-72, 107-73,
107-74, 107-75, 107-76, 107-77, 107-78, 107-79, 1
07-80, 107-81, 107-82, 107-83, 107-84, 107-85, 107
-86, 107-87, 107-88, 107-89, 107-90, 107-91, 107-9
2, 107-93, 107-94, 107-95, 107-96, 107-97,108-1, 1
08-2, 108-3, 108-4, 108-5, 108-6, 108-7, 108-8, 10
8-9, 108-10, 108-11, 108-12, 108-13, 108-14, 108-1
5, 108-16, 108-17, 108-18, 108-19, 108-20, 108-21,
108-22, 108-23, 108-24, 108-25, 108-26, 108-27, 1
08-28, 108-29, 108-30, 108-31, 108-32, 108-33, 108
-34, 108-35, 108-36, 108-37, 108-38, 108-39, 108-4
0, 108-41, 108-42, 108-43, 108-44, 108-45, 108-46,
108-47, 108-48, 108-49, 108-50, 108-51, 108-52, 1
08-53, 108-54, 108-55, 108-56, 108-57, 108-58, 108
-59, 108-60, 108-61, 108-62, 108-63, 108-64, 108-6
5, 108-66, 108-67, 108-68, 108-69, 108-70, 108-71,
108-72, 108-73, 108-74, 108-75, 108-76, 108-77, 1
08-78, 108-79, 108-80, 108-81, 108-82, 108-83, 108
-84, 108-85, 108-86, 108-87, 108-88, 108-89, 108-9
0, 108-91, 108-92, 108-93, 108-94, 108-95, 108-96,
108-97,109-1, 109-2, 109-3, 109-4, 109-5, 109-6,
109-7, 109-8, 109-9, 109-10, 109-11, 109-12, 109-1
3, 109-14, 109-15, 109-16, 109-17, 109-18, 109-19,
109-20, 109-21, 109-22, 109-23, 109-24, 109-25, 1
09-26, 109-27, 109-28, 109-29, 109-30, 109-31, 109
-32, 109-33, 109-34, 109-35, 109-36, 109-37, 109-3
8, 109-39, 109-40, 109-41, 109-42, 109-43, 109-44,
109-45, 109-46, 109-47, 109-48, 109-49, 109-50, 1
09-51, 109-52, 109-53, 109-54, 109-55, 109-56, 109
-57, 109-58, 109-59, 109-60, 109-61, 109-62, 109-6
3, 109-64, 109-65, 109-66, 109-67, 109-68, 109-69,
109-70, 109-71, 109-72, 109-73, 109-74, 109-75, 1
09-76, 109-77, 109-78, 109-79, 109-80, 109-81, 109
-82, 109-83, 109-84, 109-85, 109-86, 109-87, 109-8
8, 109-89, 109-90, 109-91, 109-92, 109-93, 109-94,
109-95, 109-96, 109-97,110-1, 110-2, 110-3, 110-
4, 110-5, 110-6, 110-7, 110-8, 110-9, 110-10, 110-
11, 110-12, 110-13, 110-14, 110-15, 110-16, 110-1
7, 110-18, 110-19, 110-20, 110-21, 110-22, 110-23,
110-24, 110-25, 110-26, 110-27, 110-28, 110-29, 1
10-30, 110-31, 110-32, 110-33, 110-34, 110-35, 110
-36, 110-37, 110-38, 110-39, 110-40, 110-41, 110-4
2, 110-43, 110-44, 110-45, 110-46, 110-47, 110-48,
110-49, 110-50, 110-51, 110-52, 110-53, 110-54, 1
10-55, 110-56, 110-57, 110-58, 110-59, 110-60, 110
-61, 110-62, 110-63, 110-64, 110-65, 110-66, 110-6
7, 110-68, 110-69, 110-70, 110-71, 110-72, 110-73,
110-74, 110-75, 110-76, 110-77, 110-78, 110-79, 1
10-80, 110-81, 110-82, 110-83, 110-84, 110-85, 110
-86, 110-87, 110-88, 110-89, 110-90, 110-91, 110-9
2, 110-93, 110-94, 110-95, 110-96, 110-97,111-1, 1
11-2, 111-3, 111-4, 111-5, 111-6, 111-7, 111-8, 11
1-9, 111-10, 111-11, 111-12, 111-13, 111-14, 111-1
5, 111-16, 111-17, 111-18, 111-19, 111-20, 111-21,
111-22, 111-23, 111-24, 111-25, 111-26, 111-27, 1
11-28, 111-29, 111-30, 111-31, 111-32, 111-33, 111
-34, 111-35, 111-36, 111-37, 111-38, 111-39, 111-4
0, 111-41, 111-42, 111-43, 111-44, 111-45, 111-46,
111-47, 111-48, 111-49, 111-50, 111-51, 111-52, 1
11-53, 111-54, 111-55, 111-56, 111-57, 111-58, 111
-59, 111-60, 111-61, 111-62, 111-63, 111-64, 111-6
5, 111-66, 111-67, 111-68, 111-69, 111-70, 111-71,
111-72, 111-73, 111-74, 111-75, 111-76, 111-77, 1
11-78, 111-79, 111-80, 111-81, 111-82, 111-83, 111
-84, 111-85, 111-86, 111-87, 111-88, 111-89, 111-9
0, 111-91, 111-92, 111-93, 111-94, 111-95, 111-96,
111-97,112-1, 112-2, 112-3, 112-4, 112-5, 112-6,
112-7, 112-8, 112-9, 112-10, 112-11, 112-12, 112-1
3, 112-14, 112-15, 112-16, 112-17, 112-18, 112-19,
112-20, 112-21, 112-22, 112-23, 112-24, 112-25, 1
12-26, 112-27, 112-28, 112-29, 112-30, 112-31, 112
-32, 112-33, 112-34, 112-35, 112-36, 112-37, 112-3
8, 112-39, 112-40, 112-41, 112-42, 112-43, 112-44,
112-45, 112-46, 112-47, 112-48, 112-49, 112-50, 1
12-51, 112-52, 112-53, 112-54, 112-55, 112-56, 112
-57, 112-58, 112-59, 112-60, 112-61, 112-62, 112-6
3, 112-64, 112-65, 112-66, 112-67, 112-68, 112-69,
112-70, 112-71, 112-72, 112-73, 112-74, 112-75, 1
12-76, 112-77, 112-78, 112-79, 112-80, 112-81, 112
-82, 112-83, 112-84, 112-85, 112-86, 112-87, 112-8
8, 112-89, 112-90, 112-91, 112-92, 112-93, 112-94,
112-95, 112-96, 112-97,113-1, 113-2, 113-3, 113-
4, 113-5, 113-6, 113-7, 113-8, 113-9, 113-10, 113-
11, 113-12, 113-13, 113-14, 113-15, 113-16, 113-1
7, 113-18, 113-19, 113-20, 113-21, 113-22, 113-23,
113-24, 113-25, 113-26, 113-27, 113-28, 113-29, 1
13-30, 113-31, 113-32, 113-33, 113-34, 113-35, 113
-36, 113-37, 113-38, 113-39, 113-40, 113-41, 113-4
2, 113-43, 113-44, 113-45, 113-46, 113-47, 113-48,
113-49, 113-50, 113-51, 113-52, 113-53, 113-54, 1
13-55, 113-56, 113-57, 113-58, 113-59, 113-60, 113
-61, 113-62, 113-63, 113-64, 113-65, 113-66, 113-6
7, 113-68, 113-69, 113-70, 113-71, 113-72, 113-73,
113-74, 113-75, 113-76, 113-77, 113-78, 113-79, 1
13-80, 113-81, 113-82, 113-83, 113-84, 113-85, 113
-86, 113-87, 113-88, 113-89, 113-90, 113-91, 113-9
2, 113-93, 113-94, 113-95, 113-96, 113-97,114-1, 1
14-2, 114-3, 114-4, 114-5, 114-6, 114-7, 114-8, 11
4-9, 114-10, 114-11, 114-12, 114-13, 114-14, 114-1
5, 114-16, 114-17, 114-18, 114-19, 114-20, 114-21,
114-22, 114-23, 114-24, 114-25, 114-26, 114-27, 1
14-28, 114-29, 114-30, 114-31, 114-32, 114-33, 114
-34, 114-35, 114-36, 114-37, 114-38, 114-39, 114-4
0, 114-41, 114-42, 114-43, 114-44, 114-45, 114-46,
114-47, 114-48, 114-49, 114-50, 114-51, 114-52, 1
14-53, 114-54, 114-55, 114-56, 114-57, 114-58, 114
-59, 114-60, 114-61, 114-62, 114-63, 114-64, 114-6
5, 114-66, 114-67, 114-68, 114-69, 114-70, 114-71,
114-72, 114-73, 114-74, 114-75, 114-76, 114-77, 1
14-78, 114-79, 114-80, 114-81, 114-82, 114-83, 114
-84, 114-85, 114-86, 114-87, 114-88, 114-89, 114-9
0, 114-91, 114-92, 114-93, 114-94, 114-95, 114-96,
114-97,115-1, 115-2, 115-3, 115-4, 115-5, 115-6,
115-7, 115-8, 115-9, 115-10, 115-11, 115-12, 115-1
3, 115-14, 115-15, 115-16, 115-17, 115-18, 115-19,
115-20, 115-21, 115-22, 115-23, 115-24, 115-25, 1
15-26, 115-27, 115-28, 115-29, 115-30, 115-31, 115
-32, 115-33, 115-34, 115-35, 115-36, 115-37, 115-3
8, 115-39, 115-40, 115-41, 115-42, 115-43, 115-44,
115-45, 115-46, 115-47, 115-48, 115-49, 115-50, 1
15-51, 115-52, 115-53, 115-54, 115-55, 115-56, 115
-57, 115-58, 115-59, 115-60, 115-61, 115-62, 115-6
3, 115-64, 115-65, 115-66, 115-67, 115-68, 115-69,
115-70, 115-71, 115-72, 115-73, 115-74, 115-75, 1
15-76, 115-77, 115-78, 115-79, 115-80, 115-81, 115
-82, 115-83, 115-84, 115-85, 115-86, 115-87, 115-8
8, 115-89, 115-90, 115-91, 115-92, 115-93, 115-94,
115-95, 115-96, 115-97,116-1, 116-2, 116-3, 116-
4, 116-5, 116-6, 116-7, 116-8, 116-9, 116-10, 116-
11, 116-12, 116-13, 116-14, 116-15, 116-16, 116-1
7, 116-18, 116-19, 116-20, 116-21, 116-22, 116-23,
116-24, 116-25, 116-26, 116-27, 116-28, 116-29, 1
16-30, 116-31, 116-32, 116-33, 116-34, 116-35, 116
-36, 116-37, 116-38, 116-39, 116-40, 116-41, 116-4
2, 116-43, 116-44, 116-45, 116-46, 116-47, 116-48,
116-49, 116-50, 116-51, 116-52, 116-53, 116-54, 1
16-55, 116-56, 116-57, 116-58, 116-59, 116-60, 116
-61, 116-62, 116-63, 116-64, 116-65, 116-66, 116-6
7, 116-68, 116-69, 116-70, 116-71, 116-72, 116-73,
116-74, 116-75, 116-76, 116-77, 116-78, 116-79, 1
16-80, 116-81, 116-82, 116-83, 116-84, 116-85, 116
-86, 116-87, 116-88, 116-89, 116-90, 116-91, 116-9
2, 116-93, 116-94, 116-95, 116-96, 116-97,117-1, 1
17-2, 117-3, 117-4, 117-5, 117-6, 117-7, 117-8, 11
7-9, 117-10, 117-11, 117-12, 117-13, 117-14, 117-1
5, 117-16, 117-17, 117-18, 117-19, 117-20, 117-21,
117-22, 117-23, 117-24, 117-25, 117-26, 117-27, 1
17-28, 117-29, 117-30, 117-31, 117-32, 117-33, 117
-34, 117-35, 117-36, 117-37, 117-38, 117-39, 117-4
0, 117-41, 117-42, 117-43, 117-44, 117-45, 117-46,
117-47, 117-48, 117-49, 117-50, 117-51, 117-52, 1
17-53, 117-54, 117-55, 117-56, 117-57, 117-58, 117
-59, 117-60, 117-61, 117-62, 117-63, 117-64, 117-6
5, 117-66, 117-67, 117-68, 117-69, 117-70, 117-71,
117-72, 117-73, 117-74, 117-75, 117-76, 117-77, 1
17-78, 117-79, 117-80, 117-81, 117-82, 117-83, 117
-84, 117-85, 117-86, 117-87, 117-88, 117-89, 117-9
0, 117-91, 117-92, 117-93, 117-94, 117-95, 117-96,
117-97,118-1, 118-2, 118-3, 118-4, 118-5, 118-6,
118-7, 118-8, 118-9, 118-10, 118-11, 118-12, 118-1
3, 118-14, 118-15, 118-16, 118-17, 118-18, 118-19,
118-20, 118-21, 118-22, 118-23, 118-24, 118-25, 1
18-26, 118-27, 118-28, 118-29, 118-30, 118-31, 118
-32, 118-33, 118-34, 118-35, 118-36, 118-37, 118-3
8, 118-39, 118-40, 118-41, 118-42, 118-43, 118-44,
118-45, 118-46, 118-47, 118-48, 118-49, 118-50, 1
18-51, 118-52, 118-53, 118-54, 118-55, 118-56, 118
-57, 118-58, 118-59, 118-60, 118-61, 118-62, 118-6
3, 118-64, 118-65, 118-66, 118-67, 118-68, 118-69,
118-70, 118-71, 118-72, 118-73, 118-74, 118-75, 1
18-76, 118-77, 118-78, 118-79, 118-80, 118-81, 118
-82, 118-83, 118-84, 118-85, 118-86, 118-87, 118-8
8, 118-89, 118-90, 118-91, 118-92, 118-93, 118-94,
118-95, 118-96, 118-97,119-1, 119-2, 119-3, 119-
4, 119-5, 119-6, 119-7, 119-8, 119-9, 119-10, 119-
11, 119-12, 119-13, 119-14, 119-15, 119-16, 119-1
7, 119-18, 119-19, 119-20, 119-21, 119-22, 119-23,
119-24, 119-25, 119-26, 119-27, 119-28, 119-29, 1
19-30, 119-31, 119-32, 119-33, 119-34, 119-35, 119
-36, 119-37, 119-38, 119-39, 119-40, 119-41, 119-4
2, 119-43, 119-44, 119-45, 119-46, 119-47, 119-48,
119-49, 119-50, 119-51, 119-52, 119-53, 119-54, 1
19-55, 119-56, 119-57, 119-58, 119-59, 119-60, 119
-61, 119-62, 119-63, 119-64, 119-65, 119-66, 119-6
7, 119-68, 119-69, 119-70, 119-71, 119-72, 119-73,
119-74, 119-75, 119-76, 119-77, 119-78, 119-79, 1
19-80, 119-81, 119-82, 119-83, 119-84, 119-85, 119
-86, 119-87, 119-88, 119-89, 119-90, 119-91, 119-9
2, 119-93, 119-94, 119-95, 119-96, 119-97,120-1, 1
20-2, 120-3, 120-4, 120-5, 120-6, 120-7, 120-8, 12
0-9, 120-10, 120-11, 120-12, 120-13, 120-14, 120-1
5, 120-16, 120-17, 120-18, 120-19, 120-20, 120-21,
120-22, 120-23, 120-24, 120-25, 120-26, 120-27, 1
20-28, 120-29, 120-30, 120-31, 120-32, 120-33, 120
-34, 120-35, 120-36, 120-37, 120-38, 120-39, 120-4
0, 120-41, 120-42, 120-43, 120-44, 120-45, 120-46,
120-47, 120-48, 120-49, 120-50, 120-51, 120-52, 1
20-53, 120-54, 120-55, 120-56, 120-57, 120-58, 120
-59, 120-60, 120-61, 120-62, 120-63, 120-64, 120-6
5, 120-66, 120-67, 120-68, 120-69, 120-70, 120-71,
120-72, 120-73, 120-74, 120-75, 120-76, 120-77, 1
20-78, 120-79, 120-80, 120-81, 120-82, 120-83, 120
-84, 120-85, 120-86, 120-87, 120-88, 120-89, 120-9
0, 120-91, 120-92, 120-93, 120-94, 120-95, 120-96,
120-97,121-1, 121-2, 121-3, 121-4, 121-5, 121-6,
121-7, 121-8, 121-9, 121-10, 121-11, 121-12, 121-1
3, 121-14, 121-15, 121-16, 121-17, 121-18, 121-19,
121-20, 121-21, 121-22, 121-23, 121-24, 121-25, 1
21-26, 121-27, 121-28, 121-29, 121-30, 121-31, 121
-32, 121-33, 121-34, 121-35, 121-36, 121-37, 121-3
8, 121-39, 121-40, 121-41, 121-42, 121-43, 121-44,
121-45, 121-46, 121-47, 121-48, 121-49, 121-50, 1
21-51, 121-52, 121-53, 121-54, 121-55, 121-56, 121
-57, 121-58, 121-59, 121-60, 121-61, 121-62, 121-6
3, 121-64, 121-65, 121-66, 121-67, 121-68, 121-69,
121-70, 121-71, 121-72, 121-73, 121-74, 121-75, 1
21-76, 121-77, 121-78, 121-79, 121-80, 121-81, 121
-82, 121-83, 121-84, 121-85, 121-86, 121-87, 121-8
8, 121-89, 121-90, 121-91, 121-92, 121-93, 121-94,
121-95, 121-96, 121-97,122-1, 122-2, 122-3, 122-
4, 122-5, 122-6, 122-7, 122-8, 122-9, 122-10, 122-
11, 122-12, 122-13, 122-14, 122-15, 122-16, 122-1
7, 122-18, 122-19, 122-20, 122-21, 122-22, 122-23,
122-24, 122-25, 122-26, 122-27, 122-28, 122-29, 1
22-30, 122-31, 122-32, 122-33, 122-34, 122-35, 122
-36, 122-37, 122-38, 122-39, 122-40, 122-41, 122-4
2, 122-43, 122-44, 122-45, 122-46, 122-47, 122-48,
122-49, 122-50, 122-51, 122-52, 122-53, 122-54, 1
22-55, 122-56, 122-57, 122-58, 122-59, 122-60, 122
-61, 122-62, 122-63, 122-64, 122-65, 122-66, 122-6
7, 122-68, 122-69, 122-70, 122-71, 122-72, 122-73,
122-74, 122-75, 122-76, 122-77, 122-78, 122-79, 1
22-80, 122-81, 122-82, 122-83, 122-84, 122-85, 122
-86, 122-87, 122-88, 122-89, 122-90, 122-91, 122-9
2, 122-93, 122-94, 122-95, 122-96, 122-97,123-1, 1
23-2, 123-3, 123-4, 123-5, 123-6, 123-7, 123-8, 12
3-9, 123-10, 123-11, 123-12, 123-13, 123-14, 123-1
5, 123-16, 123-17, 123-18, 123-19, 123-20, 123-21,
123-22, 123-23, 123-24, 123-25, 123-26, 123-27, 1
23-28, 123-29, 123-30, 123-31, 123-32, 123-33, 123
-34, 123-35, 123-36, 123-37, 123-38, 123-39, 123-4
0, 123-41, 123-42, 123-43, 123-44, 123-45, 123-46,
123-47, 123-48, 123-49, 123-50, 123-51, 123-52, 1
23-53, 123-54, 123-55, 123-56, 123-57, 123-58, 123
-59, 123-60, 123-61, 123-62, 123-63, 123-64, 123-6
5, 123-66, 123-67, 123-68, 123-69, 123-70, 123-71,
123-72, 123-73, 123-74, 123-75, 123-76, 123-77, 1
23-78, 123-79, 123-80, 123-81, 123-82, 123-83, 123
-84, 123-85, 123-86, 123-87, 123-88, 123-89, 123-9
0, 123-91, 123-92, 123-93, 123-94, 123-95, 123-96,
123-97,124-1, 124-2, 124-3, 124-4, 124-5, 124-6,
124-7, 124-8, 124-9, 124-10, 124-11, 124-12, 124-1
3, 124-14, 124-15, 124-16, 124-17, 124-18, 124-19,
124-20, 124-21, 124-22, 124-23, 124-24, 124-25, 1
24-26, 124-27, 124-28, 124-29, 124-30, 124-31, 124
-32, 124-33, 124-34, 124-35, 124-36, 124-37, 124-3
8, 124-39, 124-40, 124-41, 124-42, 124-43, 124-44,
124-45, 124-46, 124-47, 124-48, 124-49, 124-50, 1
24-51, 124-52, 124-53, 124-54, 124-55, 124-56, 124
-57, 124-58, 124-59, 124-60, 124-61, 124-62, 124-6
3, 124-64, 124-65, 124-66, 124-67, 124-68, 124-69,
124-70, 124-71, 124-72, 124-73, 124-74, 124-75, 1
24-76, 124-77, 124-78, 124-79, 124-80, 124-81, 124
-82, 124-83, 124-84, 124-85, 124-86, 124-87, 124-8
8, 124-89, 124-90, 124-91, 124-92, 124-93, 124-94,
124-95, 124-96, 124-97,125-1, 125-2, 125-3, 125-
4, 125-5, 125-6, 125-7, 125-8, 125-9, 125-10, 125-
11, 125-12, 125-13, 125-14, 125-15, 125-16, 125-1
7, 125-18, 125-19, 125-20, 125-21, 125-22, 125-23,
125-24, 125-25, 125-26, 125-27, 125-28, 125-29, 1
25-30, 125-31, 125-32, 125-33, 125-34, 125-35, 125
-36, 125-37, 125-38, 125-39, 125-40, 125-41, 125-4
2, 125-43, 125-44, 125-45, 125-46, 125-47, 125-48,
125-49, 125-50, 125-51, 125-52, 125-53, 125-54, 1
25-55, 125-56, 125-57, 125-58, 125-59, 125-60, 125
-61, 125-62, 125-63, 125-64, 125-65, 125-66, 125-6
7, 125-68, 125-69, 125-70, 125-71, 125-72, 125-73,
125-74, 125-75, 125-76, 125-77, 125-78, 125-79, 1
25-80, 125-81, 125-82, 125-83, 125-84, 125-85, 125
-86, 125-87, 125-88, 125-89, 125-90, 125-91, 125-9
2, 125-93, 125-94, 125-95, 125-96, 125-97,126-1, 1
26-2, 126-3, 126-4, 126-5, 126-6, 126-7, 126-8, 12
6-9, 126-10, 126-11, 126-12, 126-13, 126-14, 126-1
5, 126-16, 126-17, 126-18, 126-19, 126-20, 126-21,
126-22, 126-23, 126-24, 126-25, 126-26, 126-27, 1
26-28, 126-29, 126-30, 126-31, 126-32, 126-33, 126
-34, 126-35, 126-36, 126-37, 126-38, 126-39, 126-4
0, 126-41, 126-42, 126-43, 126-44, 126-45, 126-46,
126-47, 126-48, 126-49, 126-50, 126-51, 126-52, 1
26-53, 126-54, 126-55, 126-56, 126-57, 126-58, 126
-59, 126-60, 126-61, 126-62, 126-63, 126-64, 126-6
5, 126-66, 126-67, 126-68, 126-69, 126-70, 126-71,
126-72, 126-73, 126-74, 126-75, 126-76, 126-77, 1
26-78, 126-79, 126-80, 126-81, 126-82, 126-83, 126
-84, 126-85, 126-86, 126-87, 126-88, 126-89, 126-9
0, 126-91, 126-92, 126-93, 126-94, 126-95, 126-96,
126-97,127-1, 127-2, 127-3, 127-4, 127-5, 127-6,
127-7, 127-8, 127-9, 127-10, 127-11, 127-12, 127-1
3, 127-14, 127-15, 127-16, 127-17, 127-18, 127-19,
127-20, 127-21, 127-22, 127-23, 127-24, 127-25, 1
27-26, 127-27, 127-28, 127-29, 127-30, 127-31, 127
-32, 127-33, 127-34, 127-35, 127-36, 127-37, 127-3
8, 127-39, 127-40, 127-41, 127-42, 127-43, 127-44,
127-45, 127-46, 127-47, 127-48, 127-49, 127-50, 1
27-51, 127-52, 127-53, 127-54, 127-55, 127-56, 127
-57, 127-58, 127-59, 127-60, 127-61, 127-62, 127-6
3, 127-64, 127-65, 127-66, 127-67, 127-68, 127-69,
127-70, 127-71, 127-72, 127-73, 127-74, 127-75, 1
27-76, 127-77, 127-78, 127-79, 127-80, 127-81, 127
-82, 127-83, 127-84, 127-85, 127-86, 127-87, 127-8
8, 127-89, 127-90, 127-91, 127-92, 127-93, 127-94,
127-95, 127-96, 127-97,128-1, 128-2, 128-3, 128-
4, 128-5, 128-6, 128-7, 128-8, 128-9, 128-10, 128-
11, 128-12, 128-13, 128-14, 128-15, 128-16, 128-1
7, 128-18, 128-19, 128-20, 128-21, 128-22, 128-23,
128-24, 128-25, 128-26, 128-27, 128-28, 128-29, 1
28-30, 128-31, 128-32, 128-33, 128-34, 128-35, 128
-36, 128-37, 128-38, 128-39, 128-40, 128-41, 128-4
2, 128-43, 128-44, 128-45, 128-46, 128-47, 128-48,
128-49, 128-50, 128-51, 128-52, 128-53, 128-54, 1
28-55, 128-56, 128-57, 128-58, 128-59, 128-60, 128
-61, 128-62, 128-63, 128-64, 128-65, 128-66, 128-6
7, 128-68, 128-69, 128-70, 128-71, 128-72, 128-73,
128-74, 128-75, 128-76, 128-77, 128-78, 128-79, 1
28-80, 128-81, 128-82, 128-83, 128-84, 128-85, 128
-86, 128-87, 128-88, 128-89, 128-90, 128-91, 128-9
2, 128-93, 128-94, 128-95, 128-96, 128-97,129-1, 1
29-2, 129-3, 129-4, 129-5, 129-6, 129-7, 129-8, 12
9-9, 129-10, 129-11, 129-12, 129-13, 129-14, 129-1
5, 129-16, 129-17, 129-18, 129-19, 129-20, 129-21,
129-22, 129-23, 129-24, 129-25, 129-26, 129-27, 1
29-28, 129-29, 129-30, 129-31, 129-32, 129-33, 129
-34, 129-35, 129-36, 129-37, 129-38, 129-39, 129-4
0, 129-41, 129-42, 129-43, 129-44, 129-45, 129-46,
129-47, 129-48, 129-49, 129-50, 129-51, 129-52, 1
29-53, 129-54, 129-55, 129-56, 129-57, 129-58, 129
-59, 129-60, 129-61, 129-62, 129-63, 129-64, 129-6
5, 129-66, 129-67, 129-68, 129-69, 129-70, 129-71,
129-72, 129-73, 129-74, 129-75, 129-76, 129-77, 1
29-78, 129-79, 129-80, 129-81, 129-82, 129-83, 129
-84, 129-85, 129-86, 129-87, 129-88, 129-89, 129-9
0, 129-91, 129-92, 129-93, 129-94, 129-95, 129-96,
129-97,130-1, 130-2, 130-3, 130-4, 130-5, 130-6,
130-7, 130-8, 130-9, 130-10, 130-11, 130-12, 130-1
3, 130-14, 130-15, 130-16, 130-17, 130-18, 130-19,
130-20, 130-21, 130-22, 130-23, 130-24, 130-25, 1
30-26, 130-27, 130-28, 130-29, 130-30, 130-31, 130
-32, 130-33, 130-34, 130-35, 130-36, 130-37, 130-3
8, 130-39, 130-40, 130-41, 130-42, 130-43, 130-44,
130-45, 130-46, 130-47, 130-48, 130-49, 130-50, 1
30-51, 130-52, 130-53, 130-54, 130-55, 130-56, 130
-57, 130-58, 130-59, 130-60, 130-61, 130-62, 130-6
3, 130-64, 130-65, 130-66, 130-67, 130-68, 130-69,
130-70, 130-71, 130-72, 130-73, 130-74, 130-75, 1
30-76, 130-77, 130-78, 130-79, 130-80, 130-81, 130
-82, 130-83, 130-84, 130-85, 130-86, 130-87, 130-8
8, 130-89, 130-90, 130-91, 130-92, 130-93, 130-94,
130-95, 130-96, 130-97,131-1, 131-2, 131-3, 131-
4, 131-5, 131-6, 131-7, 131-8, 131-9, 131-10, 131-
11, 131-12, 131-13, 131-14, 131-15, 131-16, 131-1
7, 131-18, 131-19, 131-20, 131-21, 131-22, 131-23,
131-24, 131-25, 131-26, 131-27, 131-28, 131-29, 1
31-30, 131-31, 131-32, 131-33, 131-34, 131-35, 131
-36, 131-37, 131-38, 131-39, 131-40, 131-41, 131-4
2, 131-43, 131-44, 131-45, 131-46, 131-47, 131-48,
131-49, 131-50, 131-51, 131-52, 131-53, 131-54, 1
31-55, 131-56, 131-57, 131-58, 131-59, 131-60, 131
-61, 131-62, 131-63, 131-64, 131-65, 131-66, 131-6
7, 131-68, 131-69, 131-70, 131-71, 131-72, 131-73,
131-74, 131-75, 131-76, 131-77, 131-78, 131-79, 1
31-80, 131-81, 131-82, 131-83, 131-84, 131-85, 131
-86, 131-87, 131-88, 131-89, 131-90, 131-91, 131-9
2, 131-93, 131-94, 131-95, 131-96, 131-97,132-1, 1
32-2, 132-3, 132-4, 132-5, 132-6, 132-7, 132-8, 13
2-9, 132-10, 132-11, 132-12, 132-13, 132-14, 132-1
5, 132-16, 132-17, 132-18, 132-19, 132-20, 132-21,
132-22, 132-23, 132-24, 132-25, 132-26, 132-27, 1
32-28, 132-29, 132-30, 132-31, 132-32, 132-33, 132
-34, 132-35, 132-36, 132-37, 132-38, 132-39, 132-4
0, 132-41, 132-42, 132-43, 132-44, 132-45, 132-46,
132-47, 132-48, 132-49, 132-50, 132-51, 132-52, 1
32-53, 132-54, 132-55, 132-56, 132-57, 132-58, 132
-59, 132-60, 132-61, 132-62, 132-63, 132-64, 132-6
5, 132-66, 132-67, 132-68, 132-69, 132-70, 132-71,
132-72, 132-73, 132-74, 132-75, 132-76, 132-77, 1
32-78, 132-79, 132-80, 132-81, 132-82, 132-83, 132
-84, 132-85, 132-86, 132-87, 132-88, 132-89, 132-9
0, 132-91, 132-92, 132-93, 132-94, 132-95, 132-96,
132-97,133-1, 133-2, 133-3, 133-4, 133-5, 133-6,
133-7, 133-8, 133-9, 133-10, 133-11, 133-12, 133-1
3, 133-14, 133-15, 133-16, 133-17, 133-18, 133-19,
133-20, 133-21, 133-22, 133-23, 133-24, 133-25, 1
33-26, 133-27, 133-28, 133-29, 133-30, 133-31, 133
-32, 133-33, 133-34, 133-35, 133-36, 133-37, 133-3
8, 133-39, 133-40, 133-41, 133-42, 133-43, 133-44,
133-45, 133-46, 133-47, 133-48, 133-49, 133-50, 1
33-51, 133-52, 133-53, 133-54, 133-55, 133-56, 133
-57, 133-58, 133-59, 133-60, 133-61, 133-62, 133-6
3, 133-64, 133-65, 133-66, 133-67, 133-68, 133-69,
133-70, 133-71, 133-72, 133-73, 133-74, 133-75, 1
33-76, 133-77, 133-78, 133-79, 133-80, 133-81, 133
-82, 133-83, 133-84, 133-85, 133-86, 133-87, 133-8
8, 133-89, 133-90, 133-91, 133-92, 133-93, 133-94,
133-95, 133-96, 133-97,134-1, 134-2, 134-3, 134-
4, 134-5, 134-6, 134-7, 134-8, 134-9, 134-10, 134-
11, 134-12, 134-13, 134-14, 134-15, 134-16, 134-1
7, 134-18, 134-19, 134-20, 134-21, 134-22, 134-23,
134-24, 134-25, 134-26, 134-27, 134-28, 134-29, 1
34-30, 134-31, 134-32, 134-33, 134-34, 134-35, 134
-36, 134-37, 134-38, 134-39, 134-40, 134-41, 134-4
2, 134-43, 134-44, 134-45, 134-46, 134-47, 134-48,
134-49, 134-50, 134-51, 134-52, 134-53, 134-54, 1
34-55, 134-56, 134-57, 134-58, 134-59, 134-60, 134
-61, 134-62, 134-63, 134-64, 134-65, 134-66, 134-6
7, 134-68, 134-69, 134-70, 134-71, 134-72, 134-73,
134-74, 134-75, 134-76, 134-77, 134-78, 134-79, 1
34-80, 134-81, 134-82, 134-83, 134-84, 134-85, 134
-86, 134-87, 134-88, 134-89, 134-90, 134-91, 134-9
2, 134-93, 134-94, 134-95, 134-96, 134-97,135-1, 1
35-2, 135-3, 135-4, 135-5, 135-6, 135-7, 135-8, 13
5-9, 135-10, 135-11, 135-12, 135-13, 135-14, 135-1
5, 135-16, 135-17, 135-18, 135-19, 135-20, 135-21,
135-22, 135-23, 135-24, 135-25, 135-26, 135-27, 1
35-28, 135-29, 135-30, 135-31, 135-32, 135-33, 135
-34, 135-35, 135-36, 135-37, 135-38, 135-39, 135-4
0, 135-41, 135-42, 135-43, 135-44, 135-45, 135-46,
135-47, 135-48, 135-49, 135-50, 135-51, 135-52, 1
35-53, 135-54, 135-55, 135-56, 135-57, 135-58, 135
-59, 135-60, 135-61, 135-62, 135-63, 135-64, 135-6
5, 135-66, 135-67, 135-68, 135-69, 135-70, 135-71,
135-72, 135-73, 135-74, 135-75, 135-76, 135-77, 1
35-78, 135-79, 135-80, 135-81, 135-82, 135-83, 135
-84, 135-85, 135-86, 135-87, 135-88, 135-89, 135-9
0, 135-91, 135-92, 135-93, 135-94, 135-95, 135-96,
135-97,136-1, 136-2, 136-3, 136-4, 136-5, 136-6,
136-7, 136-8, 136-9, 136-10, 136-11, 136-12, 136-1
3, 136-14, 136-15, 136-16, 136-17, 136-18, 136-19,
136-20, 136-21, 136-22, 136-23, 136-24, 136-25, 1
36-26, 136-27, 136-28, 136-29, 136-30, 136-31, 136
-32, 136-33, 136-34, 136-35, 136-36, 136-37, 136-3
8, 136-39, 136-40, 136-41, 136-42, 136-43, 136-44,
136-45, 136-46, 136-47, 136-48, 136-49, 136-50, 1
36-51, 136-52, 136-53, 136-54, 136-55, 136-56, 136
-57, 136-58, 136-59, 136-60, 136-61, 136-62, 136-6
3, 136-64, 136-65, 136-66, 136-67, 136-68, 136-69,
136-70, 136-71, 136-72, 136-73, 136-74, 136-75, 1
36-76, 136-77, 136-78, 136-79, 136-80, 136-81, 136
-82, 136-83, 136-84, 136-85, 136-86, 136-87, 136-8
8, 136-89, 136-90, 136-91, 136-92, 136-93, 136-94,
136-95, 136-96, 136-97,137-1, 137-2, 137-3, 137-
4, 137-5, 137-6, 137-7, 137-8, 137-9, 137-10, 137-
11, 137-12, 137-13, 137-14, 137-15, 137-16, 137-1
7, 137-18, 137-19, 137-20, 137-21, 137-22, 137-23,
137-24, 137-25, 137-26, 137-27, 137-28, 137-29, 1
37-30, 137-31, 137-32, 137-33, 137-34, 137-35, 137
-36, 137-37, 137-38, 137-39, 137-40, 137-41, 137-4
2, 137-43, 137-44, 137-45, 137-46, 137-47, 137-48,
137-49, 137-50, 137-51, 137-52, 137-53, 137-54, 1
37-55, 137-56, 137-57, 137-58, 137-59, 137-60, 137
-61, 137-62, 137-63, 137-64, 137-65, 137-66, 137-6
7, 137-68, 137-69, 137-70, 137-71, 137-72, 137-73,
137-74, 137-75, 137-76, 137-77, 137-78, 137-79, 1
37-80, 137-81, 137-82, 137-83, 137-84, 137-85, 137
-86, 137-87, 137-88, 137-89, 137-90, 137-91, 137-9
2, 137-93, 137-94, 137-95, 137-96, 137-97,138-1, 1
38-2, 138-3, 138-4, 138-5, 138-6, 138-7, 138-8, 13
8-9, 138-10, 138-11, 138-12, 138-13, 138-14, 138-1
5, 138-16, 138-17, 138-18, 138-19, 138-20, 138-21,
138-22, 138-23, 138-24, 138-25, 138-26, 138-27, 1
38-28, 138-29, 138-30, 138-31, 138-32, 138-33, 138
-34, 138-35, 138-36, 138-37, 138-38, 138-39, 138-4
0, 138-41, 138-42, 138-43, 138-44, 138-45, 138-46,
138-47, 138-48, 138-49, 138-50, 138-51, 138-52, 1
38-53, 138-54, 138-55, 138-56, 138-57, 138-58, 138
-59, 138-60, 138-61, 138-62, 138-63, 138-64, 138-6
5, 138-66, 138-67, 138-68, 138-69, 138-70, 138-71,
138-72, 138-73, 138-74, 138-75, 138-76, 138-77, 1
38-78, 138-79, 138-80, 138-81, 138-82, 138-83, 138
-84, 138-85, 138-86, 138-87, 138-88, 138-89, 138-9
0, 138-91, 138-92, 138-93, 138-94, 138-95, 138-96,
138-97,139-1, 139-2, 139-3, 139-4, 139-5, 139-6,
139-7, 139-8, 139-9, 139-10, 139-11, 139-12, 139-1
3, 139-14, 139-15, 139-16, 139-17, 139-18, 139-19,
139-20, 139-21, 139-22, 139-23, 139-24, 139-25, 1
39-26, 139-27, 139-28, 139-29, 139-30, 139-31, 139
-32, 139-33, 139-34, 139-35, 139-36, 139-37, 139-3
8, 139-39, 139-40, 139-41, 139-42, 139-43, 139-44,
139-45, 139-46, 139-47, 139-48, 139-49, 139-50, 1
39-51, 139-52, 139-53, 139-54, 139-55, 139-56, 139
-57, 139-58, 139-59, 139-60, 139-61, 139-62, 139-6
3, 139-64, 139-65, 139-66, 139-67, 139-68, 139-69,
139-70, 139-71, 139-72, 139-73, 139-74, 139-75, 1
39-76, 139-77, 139-78, 139-79, 139-80, 139-81, 139
-82, 139-83, 139-84, 139-85, 139-86, 139-87, 139-8
8, 139-89, 139-90, 139-91, 139-92, 139-93, 139-94,
139-95, 139-96, 139-97,140-1, 140-2, 140-3, 140-
4, 140-5, 140-6, 140-7, 140-8, 140-9, 140-10, 140-
11, 140-12, 140-13, 140-14, 140-15, 140-16, 140-1
7, 140-18, 140-19, 140-20, 140-21, 140-22, 140-23,
140-24, 140-25, 140-26, 140-27, 140-28, 140-29, 1
40-30, 140-31, 140-32, 140-33, 140-34, 140-35, 140
-36, 140-37, 140-38, 140-39, 140-40, 140-41, 140-4
2, 140-43, 140-44, 140-45, 140-46, 140-47, 140-48,
140-49, 140-50, 140-51, 140-52, 140-53, 140-54, 1
40-55, 140-56, 140-57, 140-58, 140-59, 140-60, 140
-61, 140-62, 140-63, 140-64, 140-65, 140-66, 140-6
7, 140-68, 140-69, 140-70, 140-71, 140-72, 140-73,
140-74, 140-75, 140-76, 140-77, 140-78, 140-79, 1
40-80, 140-81, 140-82, 140-83, 140-84, 140-85, 140
-86, 140-87, 140-88, 140-89, 140-90, 140-91, 140-9
2, 140-93, 140-94, 140-95, 140-96, 140-97,141-1, 1
41-2, 141-3, 141-4, 141-5, 141-6, 141-7, 141-8, 14
1-9, 141-10, 141-11, 141-12, 141-13, 141-14, 141-1
5, 141-16, 141-17, 141-18, 141-19, 141-20, 141-21,
141-22, 141-23, 141-24, 141-25, 141-26, 141-27, 1
41-28, 141-29, 141-30, 141-31, 141-32, 141-33, 141
-34, 141-35, 141-36, 141-37, 141-38, 141-39, 141-4
0, 141-41, 141-42, 141-43, 141-44, 141-45, 141-46,
141-47, 141-48, 141-49, 141-50, 141-51, 141-52, 1
41-53, 141-54, 141-55, 141-56, 141-57, 141-58, 141
-59, 141-60, 141-61, 141-62, 141-63, 141-64, 141-6
5, 141-66, 141-67, 141-68, 141-69, 141-70, 141-71,
141-72, 141-73, 141-74, 141-75, 141-76, 141-77, 1
41-78, 141-79, 141-80, 141-81, 141-82, 141-83, 141
-84, 141-85, 141-86, 141-87, 141-88, 141-89, 141-9
0, 141-91, 141-92, 141-93, 141-94, 141-95, 141-96,
141-97,142-1, 142-2, 142-3, 142-4, 142-5, 142-6,
142-7, 142-8, 142-9, 142-10, 142-11, 142-12, 142-1
3, 142-14, 142-15, 142-16, 142-17, 142-18, 142-19,
142-20, 142-21, 142-22, 142-23, 142-24, 142-25, 1
42-26, 142-27, 142-28, 142-29, 142-30, 142-31, 142
-32, 142-33, 142-34, 142-35, 142-36, 142-37, 142-3
8, 142-39, 142-40, 142-41, 142-42, 142-43, 142-44,
142-45, 142-46, 142-47, 142-48, 142-49, 142-50, 1
42-51, 142-52, 142-53, 142-54, 142-55, 142-56, 142
-57, 142-58, 142-59, 142-60, 142-61, 142-62, 142-6
3, 142-64, 142-65, 142-66, 142-67, 142-68, 142-69,
142-70, 142-71, 142-72, 142-73, 142-74, 142-75, 1
42-76, 142-77, 142-78, 142-79, 142-80, 142-81, 142
-82, 142-83, 142-84, 142-85, 142-86, 142-87, 142-8
8, 142-89, 142-90, 142-91, 142-92, 142-93, 142-94,
142-95, 142-96, 142-97,143-1, 143-2, 143-3, 143-
4, 143-5, 143-6, 143-7, 143-8, 143-9, 143-10, 143-
11, 143-12, 143-13, 143-14, 143-15, 143-16, 143-1
7, 143-18, 143-19, 143-20, 143-21, 143-22, 143-23,
143-24, 143-25, 143-26, 143-27, 143-28, 143-29, 1
43-30, 143-31, 143-32, 143-33, 143-34, 143-35, 143
-36, 143-37, 143-38, 143-39, 143-40, 143-41, 143-4
2, 143-43, 143-44, 143-45, 143-46, 143-47, 143-48,
143-49, 143-50, 143-51, 143-52, 143-53, 143-54, 1
43-55, 143-56, 143-57, 143-58, 143-59, 143-60, 143
-61, 143-62, 143-63, 143-64, 143-65, 143-66, 143-6
7, 143-68, 143-69, 143-70, 143-71, 143-72, 143-73,
143-74, 143-75, 143-76, 143-77, 143-78, 143-79, 1
43-80, 143-81, 143-82, 143-83, 143-84, 143-85, 143
-86, 143-87, 143-88, 143-89, 143-90, 143-91, 143-9
2, 143-93, 143-94, 143-95, 143-96, 143-97,144-1, 1
44-2, 144-3, 144-4, 144-5, 144-6, 144-7, 144-8, 14
4-9, 144-10, 144-11, 144-12, 144-13, 144-14, 144-1
5, 144-16, 144-17, 144-18, 144-19, 144-20, 144-21,
144-22, 144-23, 144-24, 144-25, 144-26, 144-27, 1
44-28, 144-29, 144-30, 144-31, 144-32, 144-33, 144
-34, 144-35, 144-36, 144-37, 144-38, 144-39, 144-4
0, 144-41, 144-42, 144-43, 144-44, 144-45, 144-46,
144-47, 144-48, 144-49, 144-50, 144-51, 144-52, 1
44-53, 144-54, 144-55, 144-56, 144-57, 144-58, 144
-59, 144-60, 144-61, 144-62, 144-63, 144-64, 144-6
5, 144-66, 144-67, 144-68, 144-69, 144-70, 144-71,
144-72, 144-73, 144-74, 144-75, 144-76, 144-77, 1
44-78, 144-79, 144-80, 144-81, 144-82, 144-83, 144
-84, 144-85, 144-86, 144-87, 144-88, 144-89, 144-9
0, 144-91, 144-92, 144-93, 144-94, 144-95, 144-96,
144-97,145-1, 145-2, 145-3, 145-4, 145-5, 145-6,
145-7, 145-8, 145-9, 145-10, 145-11, 145-12, 145-1
3, 145-14, 145-15, 145-16, 145-17, 145-18, 145-19,
145-20, 145-21, 145-22, 145-23, 145-24, 145-25, 1
45-26, 145-27, 145-28, 145-29, 145-30, 145-31, 145
-32, 145-33, 145-34, 145-35, 145-36, 145-37, 145-3
8, 145-39, 145-40, 145-41, 145-42, 145-43, 145-44,
145-45, 145-46, 145-47, 145-48, 145-49, 145-50, 1
45-51, 145-52, 145-53, 145-54, 145-55, 145-56, 145
-57, 145-58, 145-59, 145-60, 145-61, 145-62, 145-6
3, 145-64, 145-65, 145-66, 145-67, 145-68, 145-69,
145-70, 145-71, 145-72, 145-73, 145-74, 145-75, 1
45-76, 145-77, 145-78, 145-79, 145-80, 145-81, 145
-82, 145-83, 145-84, 145-85, 145-86, 145-87, 145-8
8, 145-89, 145-90, 145-91, 145-92, 145-93, 145-94,
145-95, 145-96, 145-97,146-1, 146-2, 146-3, 146-
4, 146-5, 146-6, 146-7, 146-8, 146-9, 146-10, 146-
11, 146-12, 146-13, 146-14, 146-15, 146-16, 146-1
7, 146-18, 146-19, 146-20, 146-21, 146-22, 146-23,
146-24, 146-25, 146-26, 146-27, 146-28, 146-29, 1
46-30, 146-31, 146-32, 146-33, 146-34, 146-35, 146
-36, 146-37, 146-38, 146-39, 146-40, 146-41, 146-4
2, 146-43, 146-44, 146-45, 146-46, 146-47, 146-48,
146-49, 146-50, 146-51, 146-52, 146-53, 146-54, 1
46-55, 146-56, 146-57, 146-58, 146-59, 146-60, 146
-61, 146-62, 146-63, 146-64, 146-65, 146-66, 146-6
7, 146-68, 146-69, 146-70, 146-71, 146-72, 146-73,
146-74, 146-75, 146-76, 146-77, 146-78, 146-79, 1
46-80, 146-81, 146-82, 146-83, 146-84, 146-85, 146
-86, 146-87, 146-88, 146-89, 146-90, 146-91, 146-9
2, 146-93, 146-94, 146-95, 146-96, 146-97,147-1, 1
47-2, 147-3, 147-4, 147-5, 147-6, 147-7, 147-8, 14
7-9, 147-10, 147-11, 147-12, 147-13, 147-14, 147-1
5, 147-16, 147-17, 147-18, 147-19, 147-20, 147-21,
147-22, 147-23, 147-24, 147-25, 147-26, 147-27, 1
47-28, 147-29, 147-30, 147-31, 147-32, 147-33, 147
-34, 147-35, 147-36, 147-37, 147-38, 147-39, 147-4
0, 147-41, 147-42, 147-43, 147-44, 147-45, 147-46,
147-47, 147-48, 147-49, 147-50, 147-51, 147-52, 1
47-53, 147-54, 147-55, 147-56, 147-57, 147-58, 147
-59, 147-60, 147-61, 147-62, 147-63, 147-64, 147-6
5, 147-66, 147-67, 147-68, 147-69, 147-70, 147-71,
147-72, 147-73, 147-74, 147-75, 147-76, 147-77, 1
47-78, 147-79, 147-80, 147-81, 147-82, 147-83, 147
-84, 147-85, 147-86, 147-87, 147-88, 147-89, 147-9
0, 147-91, 147-92, 147-93, 147-94, 147-95, 147-96,
147-97,148-1, 148-2, 148-3, 148-4, 148-5, 148-6,
148-7, 148-8, 148-9, 148-10, 148-11, 148-12, 148-1
3, 148-14, 148-15, 148-16, 148-17, 148-18, 148-19,
148-20, 148-21, 148-22, 148-23, 148-24, 148-25, 1
48-26, 148-27, 148-28, 148-29, 148-30, 148-31, 148
-32, 148-33, 148-34, 148-35, 148-36, 148-37, 148-3
8, 148-39, 148-40, 148-41, 148-42, 148-43, 148-44,
148-45, 148-46, 148-47, 148-48, 148-49, 148-50, 1
48-51, 148-52, 148-53, 148-54, 148-55, 148-56, 148
-57, 148-58, 148-59, 148-60, 148-61, 148-62, 148-6
3, 148-64, 148-65, 148-66, 148-67, 148-68, 148-69,
148-70, 148-71, 148-72, 148-73, 148-74, 148-75, 1
48-76, 148-77, 148-78, 148-79, 148-80, 148-81, 148
-82, 148-83, 148-84, 148-85, 148-86, 148-87, 148-8
8, 148-89, 148-90, 148-91, 148-92, 148-93, 148-94,
148-95, 148-96, 148-97,149-1, 149-2, 149-3, 149-
4, 149-5, 149-6, 149-7, 149-8, 149-9, 149-10, 149-
11, 149-12, 149-13, 149-14, 149-15, 149-16, 149-1
7, 149-18, 149-19, 149-20, 149-21, 149-22, 149-23,
149-24, 149-25, 149-26, 149-27, 149-28, 149-29, 1
49-30, 149-31, 149-32, 149-33, 149-34, 149-35, 149
-36, 149-37, 149-38, 149-39, 149-40, 149-41, 149-4
2, 149-43, 149-44, 149-45, 149-46, 149-47, 149-48,
149-49, 149-50, 149-51, 149-52, 149-53, 149-54, 1
49-55, 149-56, 149-57, 149-58, 149-59, 149-60, 149
-61, 149-62, 149-63, 149-64, 149-65, 149-66, 149-6
7, 149-68, 149-69, 149-70, 149-71, 149-72, 149-73,
149-74, 149-75, 149-76, 149-77, 149-78, 149-79, 1
49-80, 149-81, 149-82, 149-83, 149-84, 149-85, 149
-86, 149-87, 149-88, 149-89, 149-90, 149-91, 149-9
2, 149-93, 149-94, 149-95, 149-96, 149-97,150-1, 1
50-2, 150-3, 150-4, 150-5, 150-6, 150-7, 150-8, 15
0-9, 150-10, 150-11, 150-12, 150-13, 150-14, 150-1
5, 150-16, 150-17, 150-18, 150-19, 150-20, 150-21,
150-22, 150-23, 150-24, 150-25, 150-26, 150-27, 1
50-28, 150-29, 150-30, 150-31, 150-32, 150-33, 150
-34, 150-35, 150-36, 150-37, 150-38, 150-39, 150-4
0, 150-41, 150-42, 150-43, 150-44, 150-45, 150-46,
150-47, 150-48, 150-49, 150-50, 150-51, 150-52, 1
50-53, 150-54, 150-55, 150-56, 150-57, 150-58, 150
-59, 150-60, 150-61, 150-62, 150-63, 150-64, 150-6
5, 150-66, 150-67, 150-68, 150-69, 150-70, 150-71,
150-72, 150-73, 150-74, 150-75, 150-76, 150-77, 1
50-78, 150-79, 150-80, 150-81, 150-82, 150-83, 150
-84, 150-85, 150-86, 150-87, 150-88, 150-89, 150-9
0, 150-91, 150-92, 150-93, 150-94, 150-95, 150-96,
150-97,151-1, 151-2, 151-3, 151-4, 151-5, 151-6,
151-7, 151-8, 151-9, 151-10, 151-11, 151-12, 151-1
3, 151-14, 151-15, 151-16, 151-17, 151-18, 151-19,
151-20, 151-21, 151-22, 151-23, 151-24, 151-25, 1
51-26, 151-27, 151-28, 151-29, 151-30, 151-31, 151
-32, 151-33, 151-34, 151-35, 151-36, 151-37, 151-3
8, 151-39, 151-40, 151-41, 151-42, 151-43, 151-44,
151-45, 151-46, 151-47, 151-48, 151-49, 151-50, 1
51-51, 151-52, 151-53, 151-54, 151-55, 151-56, 151
-57, 151-58, 151-59, 151-60, 151-61, 151-62, 151-6
3, 151-64, 151-65, 151-66, 151-67, 151-68, 151-69,
151-70, 151-71, 151-72, 151-73, 151-74, 151-75, 1
51-76, 151-77, 151-78, 151-79, 151-80, 151-81, 151
-82, 151-83, 151-84, 151-85, 151-86, 151-87, 151-8
8, 151-89, 151-90, 151-91, 151-92, 151-93, 151-94,
151-95, 151-96, 151-97,152-1, 152-2, 152-3, 152-
4, 152-5, 152-6, 152-7, 152-8, 152-9, 152-10, 152-
11, 152-12, 152-13, 152-14, 152-15, 152-16, 152-1
7, 152-18, 152-19, 152-20, 152-21, 152-22, 152-23,
152-24, 152-25, 152-26, 152-27, 152-28, 152-29, 1
52-30, 152-31, 152-32, 152-33, 152-34, 152-35, 152
-36, 152-37, 152-38, 152-39, 152-40, 152-41, 152-4
2, 152-43, 152-44, 152-45, 152-46, 152-47, 152-48,
152-49, 152-50, 152-51, 152-52, 152-53, 152-54, 1
52-55, 152-56, 152-57, 152-58, 152-59, 152-60, 152
-61, 152-62, 152-63, 152-64, 152-65, 152-66, 152-6
7, 152-68, 152-69, 152-70, 152-71, 152-72, 152-73,
152-74, 152-75, 152-76, 152-77, 152-78, 152-79, 1
52-80, 152-81, 152-82, 152-83, 152-84, 152-85, 152
-86, 152-87, 152-88, 152-89, 152-90, 152-91, 152-9
2, 152-93, 152-94, 152-95, 152-96, 152-97,153-1, 1
53-2, 153-3, 153-4, 153-5, 153-6, 153-7, 153-8, 15
3-9, 153-10, 153-11, 153-12, 153-13, 153-14, 153-1
5, 153-16, 153-17, 153-18, 153-19, 153-20, 153-21,
153-22, 153-23, 153-24, 153-25, 153-26, 153-27, 1
53-28, 153-29, 153-30, 153-31, 153-32, 153-33, 153
-34, 153-35, 153-36, 153-37, 153-38, 153-39, 153-4
0, 153-41, 153-42, 153-43, 153-44, 153-45, 153-46,
153-47, 153-48, 153-49, 153-50, 153-51, 153-52, 1
53-53, 153-54, 153-55, 153-56, 153-57, 153-58, 153
-59, 153-60, 153-61, 153-62, 153-63, 153-64, 153-6
5, 153-66, 153-67, 153-68, 153-69, 153-70, 153-71,
153-72, 153-73, 153-74, 153-75, 153-76, 153-77, 1
53-78, 153-79, 153-80, 153-81, 153-82, 153-83, 153
-84, 153-85, 153-86, 153-87, 153-88, 153-89, 153-9
0, 153-91, 153-92, 153-93, 153-94, 153-95, 153-96,
153-97,154-1, 154-2, 154-3, 154-4, 154-5, 154-6,
154-7, 154-8, 154-9, 154-10, 154-11, 154-12, 154-1
3, 154-14, 154-15, 154-16, 154-17, 154-18, 154-19,
154-20, 154-21, 154-22, 154-23, 154-24, 154-25, 1
54-26, 154-27, 154-28, 154-29, 154-30, 154-31, 154
-32, 154-33, 154-34, 154-35, 154-36, 154-37, 154-3
8, 154-39, 154-40, 154-41, 154-42, 154-43, 154-44,
154-45, 154-46, 154-47, 154-48, 154-49, 154-50, 1
54-51, 154-52, 154-53, 154-54, 154-55, 154-56, 154
-57, 154-58, 154-59, 154-60, 154-61, 154-62, 154-6
3, 154-64, 154-65, 154-66, 154-67, 154-68, 154-69,
154-70, 154-71, 154-72, 154-73, 154-74, 154-75, 1
54-76, 154-77, 154-78, 154-79, 154-80, 154-81, 154
-82, 154-83, 154-84, 154-85, 154-86, 154-87, 154-8
8, 154-89, 154-90, 154-91, 154-92, 154-93, 154-94,
154-95, 154-96, 154-97,155-1, 155-2, 155-3, 155-
4, 155-5, 155-6, 155-7, 155-8, 155-9, 155-10, 155-
11, 155-12, 155-13, 155-14, 155-15, 155-16, 155-1
7, 155-18, 155-19, 155-20, 155-21, 155-22, 155-23,
155-24, 155-25, 155-26, 155-27, 155-28, 155-29, 1
55-30, 155-31, 155-32, 155-33, 155-34, 155-35, 155
-36, 155-37, 155-38, 155-39, 155-40, 155-41, 155-4
2, 155-43, 155-44, 155-45, 155-46, 155-47, 155-48,
155-49, 155-50, 155-51, 155-52, 155-53, 155-54, 1
55-55, 155-56, 155-57, 155-58, 155-59, 155-60, 155
-61, 155-62, 155-63, 155-64, 155-65, 155-66, 155-6
7, 155-68, 155-69, 155-70, 155-71, 155-72, 155-73,
155-74, 155-75, 155-76, 155-77, 155-78, 155-79, 1
55-80, 155-81, 155-82, 155-83, 155-84, 155-85, 155
-86, 155-87, 155-88, 155-89, 155-90, 155-91, 155-9
2, 155-93, 155-94, 155-95, 155-96, 155-97,156-1, 1
56-2, 156-3, 156-4, 156-5, 156-6, 156-7, 156-8, 15
6-9, 156-10, 156-11, 156-12, 156-13, 156-14, 156-1
5, 156-16, 156-17, 156-18, 156-19, 156-20, 156-21,
156-22, 156-23, 156-24, 156-25, 156-26, 156-27, 1
56-28, 156-29, 156-30, 156-31, 156-32, 156-33, 156
-34, 156-35, 156-36, 156-37, 156-38, 156-39, 156-4
0, 156-41, 156-42, 156-43, 156-44, 156-45, 156-46,
156-47, 156-48, 156-49, 156-50, 156-51, 156-52, 1
56-53, 156-54, 156-55, 156-56, 156-57, 156-58, 156
-59, 156-60, 156-61, 156-62, 156-63, 156-64, 156-6
5, 156-66, 156-67, 156-68, 156-69, 156-70, 156-71,
156-72, 156-73, 156-74, 156-75, 156-76, 156-77, 1
56-78, 156-79, 156-80, 156-81, 156-82, 156-83, 156
-84, 156-85, 156-86, 156-87, 156-88, 156-89, 156-9
0, 156-91, 156-92, 156-93, 156-94, 156-95, 156-96,
156-97,157-1, 157-2, 157-3, 157-4, 157-5, 157-6,
157-7, 157-8, 157-9, 157-10, 157-11, 157-12, 157-1
3, 157-14, 157-15, 157-16, 157-17, 157-18, 157-19,
157-20, 157-21, 157-22, 157-23, 157-24, 157-25, 1
57-26, 157-27, 157-28, 157-29, 157-30, 157-31, 157
-32, 157-33, 157-34, 157-35, 157-36, 157-37, 157-3
8, 157-39, 157-40, 157-41, 157-42, 157-43, 157-44,
157-45, 157-46, 157-47, 157-48, 157-49, 157-50, 1
57-51, 157-52, 157-53, 157-54, 157-55, 157-56, 157
-57, 157-58, 157-59, 157-60, 157-61, 157-62, 157-6
3, 157-64, 157-65, 157-66, 157-67, 157-68, 157-69,
157-70, 157-71, 157-72, 157-73, 157-74, 157-75, 1
57-76, 157-77, 157-78, 157-79, 157-80, 157-81, 157
-82, 157-83, 157-84, 157-85, 157-86, 157-87, 157-8
8, 157-89, 157-90, 157-91, 157-92, 157-93, 157-94,
157-95, 157-96, 157-97,158-1, 158-2, 158-3, 158-
4, 158-5, 158-6, 158-7, 158-8, 158-9, 158-10, 158-
11, 158-12, 158-13, 158-14, 158-15, 158-16, 158-1
7, 158-18, 158-19, 158-20, 158-21, 158-22, 158-23,
158-24, 158-25, 158-26, 158-27, 158-28, 158-29, 1
58-30, 158-31, 158-32, 158-33, 158-34, 158-35, 158
-36, 158-37, 158-38, 158-39, 158-40, 158-41, 158-4
2, 158-43, 158-44, 158-45, 158-46, 158-47, 158-48,
158-49, 158-50, 158-51, 158-52, 158-53, 158-54, 1
58-55, 158-56, 158-57, 158-58, 158-59, 158-60, 158
-61, 158-62, 158-63, 158-64, 158-65, 158-66, 158-6
7, 158-68, 158-69, 158-70, 158-71, 158-72, 158-73,
158-74, 158-75, 158-76, 158-77, 158-78, 158-79, 1
58-80, 158-81, 158-82, 158-83, 158-84, 158-85, 158
-86, 158-87, 158-88, 158-89, 158-90, 158-91, 158-9
2, 158-93, 158-94, 158-95, 158-96, 158-97,159-1, 1
59-2, 159-3, 159-4, 159-5, 159-6, 159-7, 159-8, 15
9-9, 159-10, 159-11, 159-12, 159-13, 159-14, 159-1
5, 159-16, 159-17, 159-18, 159-19, 159-20, 159-21,
159-22, 159-23, 159-24, 159-25, 159-26, 159-27, 1
59-28, 159-29, 159-30, 159-31, 159-32, 159-33, 159
-34, 159-35, 159-36, 159-37, 159-38, 159-39, 159-4
0, 159-41, 159-42, 159-43, 159-44, 159-45, 159-46,
159-47, 159-48, 159-49, 159-50, 159-51, 159-52, 1
59-53, 159-54, 159-55, 159-56, 159-57, 159-58, 159
-59, 159-60, 159-61, 159-62, 159-63, 159-64, 159-6
5, 159-66, 159-67, 159-68, 159-69, 159-70, 159-71,
159-72, 159-73, 159-74, 159-75, 159-76, 159-77, 1
59-78, 159-79, 159-80, 159-81, 159-82, 159-83, 159
-84, 159-85, 159-86, 159-87, 159-88, 159-89, 159-9
0, 159-91, 159-92, 159-93, 159-94, 159-95, 159-96,
159-97,160-1, 160-2, 160-3, 160-4, 160-5, 160-6,
160-7, 160-8, 160-9, 160-10, 160-11, 160-12, 160-1
3, 160-14, 160-15, 160-16, 160-17, 160-18, 160-19,
160-20, 160-21, 160-22, 160-23, 160-24, 160-25, 1
60-26, 160-27, 160-28, 160-29, 160-30, 160-31, 160
-32, 160-33, 160-34, 160-35, 160-36, 160-37, 160-3
8, 160-39, 160-40, 160-41, 160-42, 160-43, 160-44,
160-45, 160-46, 160-47, 160-48, 160-49, 160-50, 1
60-51, 160-52, 160-53, 160-54, 160-55, 160-56, 160
-57, 160-58, 160-59, 160-60, 160-61, 160-62, 160-6
3, 160-64, 160-65, 160-66, 160-67, 160-68, 160-69,
160-70, 160-71, 160-72, 160-73, 160-74, 160-75, 1
60-76, 160-77, 160-78, 160-79, 160-80, 160-81, 160
-82, 160-83, 160-84, 160-85, 160-86, 160-87, 160-8
8, 160-89, 160-90, 160-91, 160-92, 160-93, 160-94,
160-95, 160-96, 160-97,161-1, 161-2, 161-3, 161-
4, 161-5, 161-6, 161-7, 161-8, 161-9, 161-10, 161-
11, 161-12, 161-13, 161-14, 161-15, 161-16, 161-1
7, 161-18, 161-19, 161-20, 161-21, 161-22, 161-23,
161-24, 161-25, 161-26, 161-27, 161-28, 161-29, 1
61-30, 161-31, 161-32, 161-33, 161-34, 161-35, 161
-36, 161-37, 161-38, 161-39, 161-40, 161-41, 161-4
2, 161-43, 161-44, 161-45, 161-46, 161-47, 161-48,
161-49, 161-50, 161-51, 161-52, 161-53, 161-54, 1
61-55, 161-56, 161-57, 161-58, 161-59, 161-60, 161
-61, 161-62, 161-63, 161-64, 161-65, 161-66, 161-6
7, 161-68, 161-69, 161-70, 161-71, 161-72, 161-73,
161-74, 161-75, 161-76, 161-77, 161-78, 161-79, 1
61-80, 161-81, 161-82, 161-83, 161-84, 161-85, 161
-86, 161-87, 161-88, 161-89, 161-90, 161-91, 161-9
2, 161-93, 161-94, 161-95, 161-96, 161-97,162-1, 1
62-2, 162-3, 162-4, 162-5, 162-6, 162-7, 162-8, 16
2-9, 162-10, 162-11, 162-12, 162-13, 162-14, 162-1
5, 162-16, 162-17, 162-18, 162-19, 162-20, 162-21,
162-22, 162-23, 162-24, 162-25, 162-26, 162-27, 1
62-28, 162-29, 162-30, 162-31, 162-32, 162-33, 162
-34, 162-35, 162-36, 162-37, 162-38, 162-39, 162-4
0, 162-41, 162-42, 162-43, 162-44, 162-45, 162-46,
162-47, 162-48, 162-49, 162-50, 162-51, 162-52, 1
62-53, 162-54, 162-55, 162-56, 162-57, 162-58, 162
-59, 162-60, 162-61, 162-62, 162-63, 162-64, 162-6
5, 162-66, 162-67, 162-68, 162-69, 162-70, 162-71,
162-72, 162-73, 162-74, 162-75, 162-76, 162-77, 1
62-78, 162-79, 162-80, 162-81, 162-82, 162-83, 162
-84, 162-85, 162-86, 162-87, 162-88, 162-89, 162-9
0, 162-91, 162-92, 162-93, 162-94, 162-95, 162-96,
162-97,163-1, 163-2, 163-3, 163-4, 163-5, 163-6,
163-7, 163-8, 163-9, 163-10, 163-11, 163-12, 163-1
3, 163-14, 163-15, 163-16, 163-17, 163-18, 163-19,
163-20, 163-21, 163-22, 163-23, 163-24, 163-25, 1
63-26, 163-27, 163-28, 163-29, 163-30, 163-31, 163
-32, 163-33, 163-34, 163-35, 163-36, 163-37, 163-3
8, 163-39, 163-40, 163-41, 163-42, 163-43, 163-44,
163-45, 163-46, 163-47, 163-48, 163-49, 163-50, 1
63-51, 163-52, 163-53, 163-54, 163-55, 163-56, 163
-57, 163-58, 163-59, 163-60, 163-61, 163-62, 163-6
3, 163-64, 163-65, 163-66, 163-67, 163-68, 163-69,
163-70, 163-71, 163-72, 163-73, 163-74, 163-75, 1
63-76, 163-77, 163-78, 163-79, 163-80, 163-81, 163
-82, 163-83, 163-84, 163-85, 163-86, 163-87, 163-8
8, 163-89, 163-90, 163-91, 163-92, 163-93, 163-94,
163-95, 163-96, 163-97,164-1, 164-2, 164-3, 164-
4, 164-5, 164-6, 164-7, 164-8, 164-9, 164-10, 164-
11, 164-12, 164-13, 164-14, 164-15, 164-16, 164-1
7, 164-18, 164-19, 164-20, 164-21, 164-22, 164-23,
164-24, 164-25, 164-26, 164-27, 164-28, 164-29, 1
64-30, 164-31, 164-32, 164-33, 164-34, 164-35, 164
-36, 164-37, 164-38, 164-39, 164-40, 164-41, 164-4
2, 164-43, 164-44, 164-45, 164-46, 164-47, 164-48,
164-49, 164-50, 164-51, 164-52, 164-53, 164-54, 1
64-55, 164-56, 164-57, 164-58, 164-59, 164-60, 164
-61, 164-62, 164-63, 164-64, 164-65, 164-66, 164-6
7, 164-68, 164-69, 164-70, 164-71, 164-72, 164-73,
164-74, 164-75, 164-76, 164-77, 164-78, 164-79, 1
64-80, 164-81, 164-82, 164-83, 164-84, 164-85, 164
-86, 164-87, 164-88, 164-89, 164-90, 164-91, 164-9
2, 164-93, 164-94, 164-95, 164-96, 164-97,165-1, 1
65-2, 165-3, 165-4, 165-5, 165-6, 165-7, 165-8, 16
5-9, 165-10, 165-11, 165-12, 165-13, 165-14, 165-1
5, 165-16, 165-17, 165-18, 165-19, 165-20, 165-21,
165-22, 165-23, 165-24, 165-25, 165-26, 165-27, 1
65-28, 165-29, 165-30, 165-31, 165-32, 165-33, 165
-34, 165-35, 165-36, 165-37, 165-38, 165-39, 165-4
0, 165-41, 165-42, 165-43, 165-44, 165-45, 165-46,
165-47, 165-48, 165-49, 165-50, 165-51, 165-52, 1
65-53, 165-54, 165-55, 165-56, 165-57, 165-58, 165
-59, 165-60, 165-61, 165-62, 165-63, 165-64, 165-6
5, 165-66, 165-67, 165-68, 165-69, 165-70, 165-71,
165-72, 165-73, 165-74, 165-75, 165-76, 165-77, 1
65-78, 165-79, 165-80, 165-81, 165-82, 165-83, 165
-84, 165-85, 165-86, 165-87, 165-88, 165-89, 165-9
0, 165-91, 165-92, 165-93, 165-94, 165-95, 165-96,
165-97,166-1, 166-2, 166-3, 166-4, 166-5, 166-6,
166-7, 166-8, 166-9, 166-10, 166-11, 166-12, 166-1
3, 166-14, 166-15, 166-16, 166-17, 166-18, 166-19,
166-20, 166-21, 166-22, 166-23, 166-24, 166-25, 1
66-26, 166-27, 166-28, 166-29, 166-30, 166-31, 166
-32, 166-33, 166-34, 166-35, 166-36, 166-37, 166-3
8, 166-39, 166-40, 166-41, 166-42, 166-43, 166-44,
166-45, 166-46, 166-47, 166-48, 166-49, 166-50, 1
66-51, 166-52, 166-53, 166-54, 166-55, 166-56, 166
-57, 166-58, 166-59, 166-60, 166-61, 166-62, 166-6
3, 166-64, 166-65, 166-66, 166-67, 166-68, 166-69,
166-70, 166-71, 166-72, 166-73, 166-74, 166-75, 1
66-76, 166-77, 166-78, 166-79, 166-80, 166-81, 166
-82, 166-83, 166-84, 166-85, 166-86, 166-87, 166-8
8, 166-89, 166-90, 166-91, 166-92, 166-93, 166-94,
166-95, 166-96, 166-97,167-1, 167-2, 167-3, 167-
4, 167-5, 167-6, 167-7, 167-8, 167-9, 167-10, 167-
11, 167-12, 167-13, 167-14, 167-15, 167-16, 167-1
7, 167-18, 167-19, 167-20, 167-21, 167-22, 167-23,
167-24, 167-25, 167-26, 167-27, 167-28, 167-29, 1
67-30, 167-31, 167-32, 167-33, 167-34, 167-35, 167
-36, 167-37, 167-38, 167-39, 167-40, 167-41, 167-4
2, 167-43, 167-44, 167-45, 167-46, 167-47, 167-48,
167-49, 167-50, 167-51, 167-52, 167-53, 167-54, 1
67-55, 167-56, 167-57, 167-58, 167-59, 167-60, 167
-61, 167-62, 167-63, 167-64, 167-65, 167-66, 167-6
7, 167-68, 167-69, 167-70, 167-71, 167-72, 167-73,
167-74, 167-75, 167-76, 167-77, 167-78, 167-79, 1
67-80, 167-81, 167-82, 167-83, 167-84, 167-85, 167
-86, 167-87, 167-88, 167-89, 167-90, 167-91, 167-9
2, 167-93, 167-94, 167-95, 167-96, 167-97,168-1, 1
68-2, 168-3, 168-4, 168-5, 168-6, 168-7, 168-8, 16
8-9, 168-10, 168-11, 168-12, 168-13, 168-14, 168-1
5, 168-16, 168-17, 168-18, 168-19, 168-20, 168-21,
168-22, 168-23, 168-24, 168-25, 168-26, 168-27, 1
68-28, 168-29, 168-30, 168-31, 168-32, 168-33, 168
-34, 168-35, 168-36, 168-37, 168-38, 168-39, 168-4
0, 168-41, 168-42, 168-43, 168-44, 168-45, 168-46,
168-47, 168-48, 168-49, 168-50, 168-51, 168-52, 1
68-53, 168-54, 168-55, 168-56, 168-57, 168-58, 168
-59, 168-60, 168-61, 168-62, 168-63, 168-64, 168-6
5, 168-66, 168-67, 168-68, 168-69, 168-70, 168-71,
168-72, 168-73, 168-74, 168-75, 168-76, 168-77, 1
68-78, 168-79, 168-80, 168-81, 168-82, 168-83, 168
-84, 168-85, 168-86, 168-87, 168-88, 168-89, 168-9
0, 168-91, 168-92, 168-93, 168-94, 168-95, 168-96,
168-97,169-1, 169-2, 169-3, 169-4, 169-5, 169-6,
169-7, 169-8, 169-9, 169-10, 169-11, 169-12, 169-1
3, 169-14, 169-15, 169-16, 169-17, 169-18, 169-19,
169-20, 169-21, 169-22, 169-23, 169-24, 169-25, 1
69-26, 169-27, 169-28, 169-29, 169-30, 169-31, 169
-32, 169-33, 169-34, 169-35, 169-36, 169-37, 169-3
8, 169-39, 169-40, 169-41, 169-42, 169-43, 169-44,
169-45, 169-46, 169-47, 169-48, 169-49, 169-50, 1
69-51, 169-52, 169-53, 169-54, 169-55, 169-56, 169
-57, 169-58, 169-59, 169-60, 169-61, 169-62, 169-6
3, 169-64, 169-65, 169-66, 169-67, 169-68, 169-69,
169-70, 169-71, 169-72, 169-73, 169-74, 169-75, 1
69-76, 169-77, 169-78, 169-79, 169-80, 169-81, 169
-82, 169-83, 169-84, 169-85, 169-86, 169-87, 169-8
8, 169-89, 169-90, 169-91, 169-92, 169-93, 169-94,
169-95, 169-96, 169-97,170-1, 170-2, 170-3, 170-
4, 170-5, 170-6, 170-7, 170-8, 170-9, 170-10, 170-
11, 170-12, 170-13, 170-14, 170-15, 170-16, 170-1
7, 170-18, 170-19, 170-20, 170-21, 170-22, 170-23,
170-24, 170-25, 170-26, 170-27, 170-28, 170-29, 1
70-30, 170-31, 170-32, 170-33, 170-34, 170-35, 170
-36, 170-37, 170-38, 170-39, 170-40, 170-41, 170-4
2, 170-43, 170-44, 170-45, 170-46, 170-47, 170-48,
170-49, 170-50, 170-51, 170-52, 170-53, 170-54, 1
70-55, 170-56, 170-57, 170-58, 170-59, 170-60, 170
-61, 170-62, 170-63, 170-64, 170-65, 170-66, 170-6
7, 170-68, 170-69, 170-70, 170-71, 170-72, 170-73,
170-74, 170-75, 170-76, 170-77, 170-78, 170-79, 1
70-80, 170-81, 170-82, 170-83, 170-84, 170-85, 170
-86, 170-87, 170-88, 170-89, 170-90, 170-91, 170-9
2, 170-93, 170-94, 170-95, 170-96, 170-97,171-1, 1
71-2, 171-3, 171-4, 171-5, 171-6, 171-7, 171-8, 17
1-9, 171-10, 171-11, 171-12, 171-13, 171-14, 171-1
5, 171-16, 171-17, 171-18, 171-19, 171-20, 171-21,
171-22, 171-23, 171-24, 171-25, 171-26, 171-27, 1
71-28, 171-29, 171-30, 171-31, 171-32, 171-33, 171
-34, 171-35, 171-36, 171-37, 171-38, 171-39, 171-4
0, 171-41, 171-42, 171-43, 171-44, 171-45, 171-46,
171-47, 171-48, 171-49, 171-50, 171-51, 171-52, 1
71-53, 171-54, 171-55, 171-56, 171-57, 171-58, 171
-59, 171-60, 171-61, 171-62, 171-63, 171-64, 171-6
5, 171-66, 171-67, 171-68, 171-69, 171-70, 171-71,
171-72, 171-73, 171-74, 171-75, 171-76, 171-77, 1
71-78, 171-79, 171-80, 171-81, 171-82, 171-83, 171
-84, 171-85, 171-86, 171-87, 171-88, 171-89, 171-9
0, 171-91, 171-92, 171-93, 171-94, 171-95, 171-96,
171-97,172-1, 172-2, 172-3, 172-4, 172-5, 172-6,
172-7, 172-8, 172-9, 172-10, 172-11, 172-12, 172-1
3, 172-14, 172-15, 172-16, 172-17, 172-18, 172-19,
172-20, 172-21, 172-22, 172-23, 172-24, 172-25, 1
72-26, 172-27, 172-28, 172-29, 172-30, 172-31, 172
-32, 172-33, 172-34, 172-35, 172-36, 172-37, 172-3
8, 172-39, 172-40, 172-41, 172-42, 172-43, 172-44,
172-45, 172-46, 172-47, 172-48, 172-49, 172-50, 1
72-51, 172-52, 172-53, 172-54, 172-55, 172-56, 172
-57, 172-58, 172-59, 172-60, 172-61, 172-62, 172-6
3, 172-64, 172-65, 172-66, 172-67, 172-68, 172-69,
172-70, 172-71, 172-72, 172-73, 172-74, 172-75, 1
72-76, 172-77, 172-78, 172-79, 172-80, 172-81, 172
-82, 172-83, 172-84, 172-85, 172-86, 172-87, 172-8
8, 172-89, 172-90, 172-91, 172-92, 172-93, 172-94,
172-95, 172-96, 172-97,173-1, 173-2, 173-3, 173-
4, 173-5, 173-6, 173-7, 173-8, 173-9, 173-10, 173-
11, 173-12, 173-13, 173-14, 173-15, 173-16, 173-1
7, 173-18, 173-19, 173-20, 173-21, 173-22, 173-23,
173-24, 173-25, 173-26, 173-27, 173-28, 173-29, 1
73-30, 173-31, 173-32, 173-33, 173-34, 173-35, 173
-36, 173-37, 173-38, 173-39, 173-40, 173-41, 173-4
2, 173-43, 173-44, 173-45, 173-46, 173-47, 173-48,
173-49, 173-50, 173-51, 173-52, 173-53, 173-54, 1
73-55, 173-56, 173-57, 173-58, 173-59, 173-60, 173
-61, 173-62, 173-63, 173-64, 173-65, 173-66, 173-6
7, 173-68, 173-69, 173-70, 173-71, 173-72, 173-73,
173-74, 173-75, 173-76, 173-77, 173-78, 173-79, 1
73-80, 173-81, 173-82, 173-83, 173-84, 173-85, 173
-86, 173-87, 173-88, 173-89, 173-90, 173-91, 173-9
2, 173-93, 173-94, 173-95, 173-96, 173-97,174-1, 1
74-2, 174-3, 174-4, 174-5, 174-6, 174-7, 174-8, 17
4-9, 174-10, 174-11, 174-12, 174-13, 174-14, 174-1
5, 174-16, 174-17, 174-18, 174-19, 174-20, 174-21,
174-22, 174-23, 174-24, 174-25, 174-26, 174-27, 1
74-28, 174-29, 174-30, 174-31, 174-32, 174-33, 174
-34, 174-35, 174-36, 174-37, 174-38, 174-39, 174-4
0, 174-41, 174-42, 174-43, 174-44, 174-45, 174-46,
174-47, 174-48, 174-49, 174-50, 174-51, 174-52, 1
74-53, 174-54, 174-55, 174-56, 174-57, 174-58, 174
-59, 174-60, 174-61, 174-62, 174-63, 174-64, 174-6
5, 174-66, 174-67, 174-68, 174-69, 174-70, 174-71,
174-72, 174-73, 174-74, 174-75, 174-76, 174-77, 1
74-78, 174-79, 174-80, 174-81, 174-82, 174-83, 174
-84, 174-85, 174-86, 174-87, 174-88, 174-89, 174-9
0, 174-91, 174-92, 174-93, 174-94, 174-95, 174-96,
174-97,175-1, 175-2, 175-3, 175-4, 175-5, 175-6,
175-7, 175-8, 175-9, 175-10, 175-11, 175-12, 175-1
3, 175-14, 175-15, 175-16, 175-17, 175-18, 175-19,
175-20, 175-21, 175-22, 175-23, 175-24, 175-25, 1
75-26, 175-27, 175-28, 175-29, 175-30, 175-31, 175
-32, 175-33, 175-34, 175-35, 175-36, 175-37, 175-3
8, 175-39, 175-40, 175-41, 175-42, 175-43, 175-44,
175-45, 175-46, 175-47, 175-48, 175-49, 175-50, 1
75-51, 175-52, 175-53, 175-54, 175-55, 175-56, 175
-57, 175-58, 175-59, 175-60, 175-61, 175-62, 175-6
3, 175-64, 175-65, 175-66, 175-67, 175-68, 175-69,
175-70, 175-71, 175-72, 175-73, 175-74, 175-75, 1
75-76, 175-77, 175-78, 175-79, 175-80, 175-81, 175
-82, 175-83, 175-84, 175-85, 175-86, 175-87, 175-8
8, 175-89, 175-90, 175-91, 175-92, 175-93, 175-94,
175-95, 175-96, 175-97,176-1, 176-2, 176-3, 176-
4, 176-5, 176-6, 176-7, 176-8, 176-9, 176-10, 176-
11, 176-12, 176-13, 176-14, 176-15, 176-16, 176-1
7, 176-18, 176-19, 176-20, 176-21, 176-22, 176-23,
176-24, 176-25, 176-26, 176-27, 176-28, 176-29, 1
76-30, 176-31, 176-32, 176-33, 176-34, 176-35, 176
-36, 176-37, 176-38, 176-39, 176-40, 176-41, 176-4
2, 176-43, 176-44, 176-45, 176-46, 176-47, 176-48,
176-49, 176-50, 176-51, 176-52, 176-53, 176-54, 1
76-55, 176-56, 176-57, 176-58, 176-59, 176-60, 176
-61, 176-62, 176-63, 176-64, 176-65, 176-66, 176-6
7, 176-68, 176-69, 176-70, 176-71, 176-72, 176-73,
176-74, 176-75, 176-76, 176-77, 176-78, 176-79, 1
76-80, 176-81, 176-82, 176-83, 176-84, 176-85, 176
-86, 176-87, 176-88, 176-89, 176-90, 176-91, 176-9
2, 176-93, 176-94, 176-95, 176-96, 176-97,177-1, 1
77-2, 177-3, 177-4, 177-5, 177-6, 177-7, 177-8, 17
7-9, 177-10, 177-11, 177-12, 177-13, 177-14, 177-1
5, 177-16, 177-17, 177-18, 177-19, 177-20, 177-21,
177-22, 177-23, 177-24, 177-25, 177-26, 177-27, 1
77-28, 177-29, 177-30, 177-31, 177-32, 177-33, 177
-34, 177-35, 177-36, 177-37, 177-38, 177-39, 177-4
0, 177-41, 177-42, 177-43, 177-44, 177-45, 177-46,
177-47, 177-48, 177-49, 177-50, 177-51, 177-52, 1
77-53, 177-54, 177-55, 177-56, 177-57, 177-58, 177
-59, 177-60, 177-61, 177-62, 177-63, 177-64, 177-6
5, 177-66, 177-67, 177-68, 177-69, 177-70, 177-71,
177-72, 177-73, 177-74, 177-75, 177-76, 177-77, 1
77-78, 177-79, 177-80, 177-81, 177-82, 177-83, 177
-84, 177-85, 177-86, 177-87, 177-88, 177-89, 177-9
0, 177-91, 177-92, 177-93, 177-94, 177-95, 177-96,
177-97,178-1, 178-2, 178-3, 178-4, 178-5, 178-6,
178-7, 178-8, 178-9, 178-10, 178-11, 178-12, 178-1
3, 178-14, 178-15, 178-16, 178-17, 178-18, 178-19,
178-20, 178-21, 178-22, 178-23, 178-24, 178-25, 1
78-26, 178-27, 178-28, 178-29, 178-30, 178-31, 178
-32, 178-33, 178-34, 178-35, 178-36, 178-37, 178-3
8, 178-39, 178-40, 178-41, 178-42, 178-43, 178-44,
178-45, 178-46, 178-47, 178-48, 178-49, 178-50, 1
78-51, 178-52, 178-53, 178-54, 178-55, 178-56, 178
-57, 178-58, 178-59, 178-60, 178-61, 178-62, 178-6
3, 178-64, 178-65, 178-66, 178-67, 178-68, 178-69,
178-70, 178-71, 178-72, 178-73, 178-74, 178-75, 1
78-76, 178-77, 178-78, 178-79, 178-80, 178-81, 178
-82, 178-83, 178-84, 178-85, 178-86, 178-87, 178-8
8, 178-89, 178-90, 178-91, 178-92, 178-93, 178-94,
178-95, 178-96, 178-97,179-1, 179-2, 179-3, 179-
4, 179-5, 179-6, 179-7, 179-8, 179-9, 179-10, 179-
11, 179-12, 179-13, 179-14, 179-15, 179-16, 179-1
7, 179-18, 179-19, 179-20, 179-21, 179-22, 179-23,
179-24, 179-25, 179-26, 179-27, 179-28, 179-29, 1
79-30, 179-31, 179-32, 179-33, 179-34, 179-35, 179
-36, 179-37, 179-38, 179-39, 179-40, 179-41, 179-4
2, 179-43, 179-44, 179-45, 179-46, 179-47, 179-48,
179-49, 179-50, 179-51, 179-52, 179-53, 179-54, 1
79-55, 179-56, 179-57, 179-58, 179-59, 179-60, 179
-61, 179-62, 179-63, 179-64, 179-65, 179-66, 179-6
7, 179-68, 179-69, 179-70, 179-71, 179-72, 179-73,
179-74, 179-75, 179-76, 179-77, 179-78, 179-79, 1
79-80, 179-81, 179-82, 179-83, 179-84, 179-85, 179
-86, 179-87, 179-88, 179-89, 179-90, 179-91, 179-9
2, 179-93, 179-94, 179-95, 179-96, 179-97,180-1, 1
80-2, 180-3, 180-4, 180-5, 180-6, 180-7, 180-8, 18
0-9, 180-10, 180-11, 180-12, 180-13, 180-14, 180-1
5, 180-16, 180-17, 180-18, 180-19, 180-20, 180-21,
180-22, 180-23, 180-24, 180-25, 180-26, 180-27, 1
80-28, 180-29, 180-30, 180-31, 180-32, 180-33, 180
-34, 180-35, 180-36, 180-37, 180-38, 180-39, 180-4
0, 180-41, 180-42, 180-43, 180-44, 180-45, 180-46,
180-47, 180-48, 180-49, 180-50, 180-51, 180-52, 1
80-53, 180-54, 180-55, 180-56, 180-57, 180-58, 180
-59, 180-60, 180-61, 180-62, 180-63, 180-64, 180-6
5, 180-66, 180-67, 180-68, 180-69, 180-70, 180-71,
180-72, 180-73, 180-74, 180-75, 180-76, 180-77, 1
80-78, 180-79, 180-80, 180-81, 180-82, 180-83, 180
-84, 180-85, 180-86, 180-87, 180-88, 180-89, 180-9
0, 180-91, 180-92, 180-93, 180-94, 180-95, 180-96,
180-97,181-1, 181-2, 181-3, 181-4, 181-5, 181-6,
181-7, 181-8, 181-9, 181-10, 181-11, 181-12, 181-1
3, 181-14, 181-15, 181-16, 181-17, 181-18, 181-19,
181-20, 181-21, 181-22, 181-23, 181-24, 181-25, 1
81-26, 181-27, 181-28, 181-29, 181-30, 181-31, 181
-32, 181-33, 181-34, 181-35, 181-36, 181-37, 181-3
8, 181-39, 181-40, 181-41, 181-42, 181-43, 181-44,
181-45, 181-46, 181-47, 181-48, 181-49, 181-50, 1
81-51, 181-52, 181-53, 181-54, 181-55, 181-56, 181
-57, 181-58, 181-59, 181-60, 181-61, 181-62, 181-6
3, 181-64, 181-65, 181-66, 181-67, 181-68, 181-69,
181-70, 181-71, 181-72, 181-73, 181-74, 181-75, 1
81-76, 181-77, 181-78, 181-79, 181-80, 181-81, 181
-82, 181-83, 181-84, 181-85, 181-86, 181-87, 181-8
8, 181-89, 181-90, 181-91, 181-92, 181-93, 181-94,
181-95, 181-96, 181-97,182-1, 182-2, 182-3, 182-
4, 182-5, 182-6, 182-7, 182-8, 182-9, 182-10, 182-
11, 182-12, 182-13, 182-14, 182-15, 182-16, 182-1
7, 182-18, 182-19, 182-20, 182-21, 182-22, 182-23,
182-24, 182-25, 182-26, 182-27, 182-28, 182-29, 1
82-30, 182-31, 182-32, 182-33, 182-34, 182-35, 182
-36, 182-37, 182-38, 182-39, 182-40, 182-41, 182-4
2, 182-43, 182-44, 182-45, 182-46, 182-47, 182-48,
182-49, 182-50, 182-51, 182-52, 182-53, 182-54, 1
82-55, 182-56, 182-57, 182-58, 182-59, 182-60, 182
-61, 182-62, 182-63, 182-64, 182-65, 182-66, 182-6
7, 182-68, 182-69, 182-70, 182-71, 182-72, 182-73,
182-74, 182-75, 182-76, 182-77, 182-78, 182-79, 1
82-80, 182-81, 182-82, 182-83, 182-84, 182-85, 182
-86, 182-87, 182-88, 182-89, 182-90, 182-91, 182-9
2, 182-93, 182-94, 182-95, 182-96, 182-97,183-1, 1
83-2, 183-3, 183-4, 183-5, 183-6, 183-7, 183-8, 18
3-9, 183-10, 183-11, 183-12, 183-13, 183-14, 183-1
5, 183-16, 183-17, 183-18, 183-19, 183-20, 183-21,
183-22, 183-23, 183-24, 183-25, 183-26, 183-27, 1
83-28, 183-29, 183-30, 183-31, 183-32, 183-33, 183
-34, 183-35, 183-36, 183-37, 183-38, 183-39, 183-4
0, 183-41, 183-42, 183-43, 183-44, 183-45, 183-46,
183-47, 183-48, 183-49, 183-50, 183-51, 183-52, 1
83-53, 183-54, 183-55, 183-56, 183-57, 183-58, 183
-59, 183-60, 183-61, 183-62, 183-63, 183-64, 183-6
5, 183-66, 183-67, 183-68, 183-69, 183-70, 183-71,
183-72, 183-73, 183-74, 183-75, 183-76, 183-77, 1
83-78, 183-79, 183-80, 183-81, 183-82, 183-83, 183
-84, 183-85, 183-86, 183-87, 183-88, 183-89, 183-9
0, 183-91, 183-92, 183-93, 183-94, 183-95, 183-96,
183-97,184-1, 184-2, 184-3, 184-4, 184-5, 184-6,
184-7, 184-8, 184-9, 184-10, 184-11, 184-12, 184-1
3, 184-14, 184-15, 184-16, 184-17, 184-18, 184-19,
184-20, 184-21, 184-22, 184-23, 184-24, 184-25, 1
84-26, 184-27, 184-28, 184-29, 184-30, 184-31, 184
-32, 184-33, 184-34, 184-35, 184-36, 184-37, 184-3
8, 184-39, 184-40, 184-41, 184-42, 184-43, 184-44,
184-45, 184-46, 184-47, 184-48, 184-49, 184-50, 1
84-51, 184-52, 184-53, 184-54, 184-55, 184-56, 184
-57, 184-58, 184-59, 184-60, 184-61, 184-62, 184-6
3, 184-64, 184-65, 184-66, 184-67, 184-68, 184-69,
184-70, 184-71, 184-72, 184-73, 184-74, 184-75, 1
84-76, 184-77, 184-78, 184-79, 184-80, 184-81, 184
-82, 184-83, 184-84, 184-85, 184-86, 184-87, 184-8
8, 184-89, 184-90, 184-91, 184-92, 184-93, 184-94,
184-95, 184-96, 184-97,185-1, 185-2, 185-3, 185-
4, 185-5, 185-6, 185-7, 185-8, 185-9, 185-10, 185-
11, 185-12, 185-13, 185-14, 185-15, 185-16, 185-1
7, 185-18, 185-19, 185-20, 185-21, 185-22, 185-23,
185-24, 185-25, 185-26, 185-27, 185-28, 185-29, 1
85-30, 185-31, 185-32, 185-33, 185-34, 185-35, 185
-36, 185-37, 185-38, 185-39, 185-40, 185-41, 185-4
2, 185-43, 185-44, 185-45, 185-46, 185-47, 185-48,
185-49, 185-50, 185-51, 185-52, 185-53, 185-54, 1
85-55, 185-56, 185-57, 185-58, 185-59, 185-60, 185
-61, 185-62, 185-63, 185-64, 185-65, 185-66, 185-6
7, 185-68, 185-69, 185-70, 185-71, 185-72, 185-73,
185-74, 185-75, 185-76, 185-77, 185-78, 185-79, 1
85-80, 185-81, 185-82, 185-83, 185-84, 185-85, 185
-86, 185-87, 185-88, 185-89, 185-90, 185-91, 185-9
2, 185-93, 185-94, 185-95, 185-96, 185-97,186-1, 1
86-2, 186-3, 186-4, 186-5, 186-6, 186-7, 186-8, 18
6-9, 186-10, 186-11, 186-12, 186-13, 186-14, 186-1
5, 186-16, 186-17, 186-18, 186-19, 186-20, 186-21,
186-22, 186-23, 186-24, 186-25, 186-26, 186-27, 1
86-28, 186-29, 186-30, 186-31, 186-32, 186-33, 186
-34, 186-35, 186-36, 186-37, 186-38, 186-39, 186-4
0, 186-41, 186-42, 186-43, 186-44, 186-45, 186-46,
186-47, 186-48, 186-49, 186-50, 186-51, 186-52, 1
86-53, 186-54, 186-55, 186-56, 186-57, 186-58, 186
-59, 186-60, 186-61, 186-62, 186-63, 186-64, 186-6
5, 186-66, 186-67, 186-68, 186-69, 186-70, 186-71,
186-72, 186-73, 186-74, 186-75, 186-76, 186-77, 1
86-78, 186-79, 186-80, 186-81, 186-82, 186-83, 186
-84, 186-85, 186-86, 186-87, 186-88, 186-89, 186-9
0, 186-91, 186-92, 186-93, 186-94, 186-95, 186-96,
186-97,187-1, 187-2, 187-3, 187-4, 187-5, 187-6,
187-7, 187-8, 187-9, 187-10, 187-11, 187-12, 187-1
3, 187-14, 187-15, 187-16, 187-17, 187-18, 187-19,
187-20, 187-21, 187-22, 187-23, 187-24, 187-25, 1
87-26, 187-27, 187-28, 187-29, 187-30, 187-31, 187
-32, 187-33, 187-34, 187-35, 187-36, 187-37, 187-3
8, 187-39, 187-40, 187-41, 187-42, 187-43, 187-44,
187-45, 187-46, 187-47, 187-48, 187-49, 187-50, 1
87-51, 187-52, 187-53, 187-54, 187-55, 187-56, 187
-57, 187-58, 187-59, 187-60, 187-61, 187-62, 187-6
3, 187-64, 187-65, 187-66, 187-67, 187-68, 187-69,
187-70, 187-71, 187-72, 187-73, 187-74, 187-75, 1
87-76, 187-77, 187-78, 187-79, 187-80, 187-81, 187
-82, 187-83, 187-84, 187-85, 187-86, 187-87, 187-8
8, 187-89, 187-90, 187-91, 187-92, 187-93, 187-94,
187-95, 187-96, 187-97,188-1, 188-2, 188-3, 188-
4, 188-5, 188-6, 188-7, 188-8, 188-9, 188-10, 188-
11, 188-12, 188-13, 188-14, 188-15, 188-16, 188-1
7, 188-18, 188-19, 188-20, 188-21, 188-22, 188-23,
188-24, 188-25, 188-26, 188-27, 188-28, 188-29, 1
88-30, 188-31, 188-32, 188-33, 188-34, 188-35, 188
-36, 188-37, 188-38, 188-39, 188-40, 188-41, 188-4
2, 188-43, 188-44, 188-45, 188-46, 188-47, 188-48,
188-49, 188-50, 188-51, 188-52, 188-53, 188-54, 1
88-55, 188-56, 188-57, 188-58, 188-59, 188-60, 188
-61, 188-62, 188-63, 188-64, 188-65, 188-66, 188-6
7, 188-68, 188-69, 188-70, 188-71, 188-72, 188-73,
188-74, 188-75, 188-76, 188-77, 188-78, 188-79, 1
88-80, 188-81, 188-82, 188-83, 188-84, 188-85, 188
-86, 188-87, 188-88, 188-89, 188-90, 188-91, 188-9
2, 188-93, 188-94, 188-95, 188-96, 188-97,189-1, 1
89-2, 189-3, 189-4, 189-5, 189-6, 189-7, 189-8, 18
9-9, 189-10, 189-11, 189-12, 189-13, 189-14, 189-1
5, 189-16, 189-17, 189-18, 189-19, 189-20, 189-21,
189-22, 189-23, 189-24, 189-25, 189-26, 189-27, 1
89-28, 189-29, 189-30, 189-31, 189-32, 189-33, 189
-34, 189-35, 189-36, 189-37, 189-38, 189-39, 189-4
0, 189-41, 189-42, 189-43, 189-44, 189-45, 189-46,
189-47, 189-48, 189-49, 189-50, 189-51, 189-52, 1
89-53, 189-54, 189-55, 189-56, 189-57, 189-58, 189
-59, 189-60, 189-61, 189-62, 189-63, 189-64, 189-6
5, 189-66, 189-67, 189-68, 189-69, 189-70, 189-71,
189-72, 189-73, 189-74, 189-75, 189-76, 189-77, 1
89-78, 189-79, 189-80, 189-81, 189-82, 189-83, 189
-84, 189-85, 189-86, 189-87, 189-88, 189-89, 189-9
0, 189-91, 189-92, 189-93, 189-94, 189-95, 189-96,
189-97,190-1, 190-2, 190-3, 190-4, 190-5, 190-6,
190-7, 190-8, 190-9, 190-10, 190-11, 190-12, 190-1
3, 190-14, 190-15, 190-16, 190-17, 190-18, 190-19,
190-20, 190-21, 190-22, 190-23, 190-24, 190-25, 1
90-26, 190-27, 190-28, 190-29, 190-30, 190-31, 190
-32, 190-33, 190-34, 190-35, 190-36, 190-37, 190-3
8, 190-39, 190-40, 190-41, 190-42, 190-43, 190-44,
190-45, 190-46, 190-47, 190-48, 190-49, 190-50, 1
90-51, 190-52, 190-53, 190-54, 190-55, 190-56, 190
-57, 190-58, 190-59, 190-60, 190-61, 190-62, 190-6
3, 190-64, 190-65, 190-66, 190-67, 190-68, 190-69,
190-70, 190-71, 190-72, 190-73, 190-74, 190-75, 1
90-76, 190-77, 190-78, 190-79, 190-80, 190-81, 190
-82, 190-83, 190-84, 190-85, 190-86, 190-87, 190-8
8, 190-89, 190-90, 190-91, 190-92, 190-93, 190-94,
190-95, 190-96, 190-97,191-1, 191-2, 191-3, 191-
4, 191-5, 191-6, 191-7, 191-8, 191-9, 191-10, 191-
11, 191-12, 191-13, 191-14, 191-15, 191-16, 191-1
7, 191-18, 191-19, 191-20, 191-21, 191-22, 191-23,
191-24, 191-25, 191-26, 191-27, 191-28, 191-29, 1
91-30, 191-31, 191-32, 191-33, 191-34, 191-35, 191
-36, 191-37, 191-38, 191-39, 191-40, 191-41, 191-4
2, 191-43, 191-44, 191-45, 191-46, 191-47, 191-48,
191-49, 191-50, 191-51, 191-52, 191-53, 191-54, 1
91-55, 191-56, 191-57, 191-58, 191-59, 191-60, 191
-61, 191-62, 191-63, 191-64, 191-65, 191-66, 191-6
7, 191-68, 191-69, 191-70, 191-71, 191-72, 191-73,
191-74, 191-75, 191-76, 191-77, 191-78, 191-79, 1
91-80, 191-81, 191-82, 191-83, 191-84, 191-85, 191
-86, 191-87, 191-88, 191-89, 191-90, 191-91, 191-9
2, 191-93, 191-94, 191-95, 191-96, 191-97,192-1, 1
92-2, 192-3, 192-4, 192-5, 192-6, 192-7, 192-8, 19
2-9, 192-10, 192-11, 192-12, 192-13, 192-14, 192-1
5, 192-16, 192-17, 192-18, 192-19, 192-20, 192-21,
192-22, 192-23, 192-24, 192-25, 192-26, 192-27, 1
92-28, 192-29, 192-30, 192-31, 192-32, 192-33, 192
-34, 192-35, 192-36, 192-37, 192-38, 192-39, 192-4
0, 192-41, 192-42, 192-43, 192-44, 192-45, 192-46,
192-47, 192-48, 192-49, 192-50, 192-51, 192-52, 1
92-53, 192-54, 192-55, 192-56, 192-57, 192-58, 192
-59, 192-60, 192-61, 192-62, 192-63, 192-64, 192-6
5, 192-66, 192-67, 192-68, 192-69, 192-70, 192-71,
192-72, 192-73, 192-74, 192-75, 192-76, 192-77, 1
92-78, 192-79, 192-80, 192-81, 192-82, 192-83, 192
-84, 192-85, 192-86, 192-87, 192-88, 192-89, 192-9
0, 192-91, 192-92, 192-93, 192-94, 192-95, 192-96,
192-97,193-1, 193-2, 193-3, 193-4, 193-5, 193-6,
193-7, 193-8, 193-9, 193-10, 193-11, 193-12, 193-1
3, 193-14, 193-15, 193-16, 193-17, 193-18, 193-19,
193-20, 193-21, 193-22, 193-23, 193-24, 193-25, 1
93-26, 193-27, 193-28, 193-29, 193-30, 193-31, 193
-32, 193-33, 193-34, 193-35, 193-36, 193-37, 193-3
8, 193-39, 193-40, 193-41, 193-42, 193-43, 193-44,
193-45, 193-46, 193-47, 193-48, 193-49, 193-50, 1
93-51, 193-52, 193-53, 193-54, 193-55, 193-56, 193
-57, 193-58, 193-59, 193-60, 193-61, 193-62, 193-6
3, 193-64, 193-65, 193-66, 193-67, 193-68, 193-69,
193-70, 193-71, 193-72, 193-73, 193-74, 193-75, 1
93-76, 193-77, 193-78, 193-79, 193-80, 193-81, 193
-82, 193-83, 193-84, 193-85, 193-86, 193-87, 193-8
8, 193-89, 193-90, 193-91, 193-92, 193-93, 193-94,
193-95, 193-96, 193-97,194-1, 194-2, 194-3, 194-
4, 194-5, 194-6, 194-7, 194-8, 194-9, 194-10, 194-
11, 194-12, 194-13, 194-14, 194-15, 194-16, 194-1
7, 194-18, 194-19, 194-20, 194-21, 194-22, 194-23,
194-24, 194-25, 194-26, 194-27, 194-28, 194-29, 1
94-30, 194-31, 194-32, 194-33, 194-34, 194-35, 194
-36, 194-37, 194-38, 194-39, 194-40, 194-41, 194-4
2, 194-43, 194-44, 194-45, 194-46, 194-47, 194-48,
194-49, 194-50, 194-51, 194-52, 194-53, 194-54, 1
94-55, 194-56, 194-57, 194-58, 194-59, 194-60, 194
-61, 194-62, 194-63, 194-64, 194-65, 194-66, 194-6
7, 194-68, 194-69, 194-70, 194-71, 194-72, 194-73,
194-74, 194-75, 194-76, 194-77, 194-78, 194-79, 1
94-80, 194-81, 194-82, 194-83, 194-84, 194-85, 194
-86, 194-87, 194-88, 194-89, 194-90, 194-91, 194-9
2, 194-93, 194-94, 194-95, 194-96, 194-97,195-1, 1
95-2, 195-3, 195-4, 195-5, 195-6, 195-7, 195-8, 19
5-9, 195-10, 195-11, 195-12, 195-13, 195-14, 195-1
5, 195-16, 195-17, 195-18, 195-19, 195-20, 195-21,
195-22, 195-23, 195-24, 195-25, 195-26, 195-27, 1
95-28, 195-29, 195-30, 195-31, 195-32, 195-33, 195
-34, 195-35, 195-36, 195-37, 195-38, 195-39, 195-4
0, 195-41, 195-42, 195-43, 195-44, 195-45, 195-46,
195-47, 195-48, 195-49, 195-50, 195-51, 195-52, 1
95-53, 195-54, 195-55, 195-56, 195-57, 195-58, 195
-59, 195-60, 195-61, 195-62, 195-63, 195-64, 195-6
5, 195-66, 195-67, 195-68, 195-69, 195-70, 195-71,
195-72, 195-73, 195-74, 195-75, 195-76, 195-77, 1
95-78, 195-79, 195-80, 195-81, 195-82, 195-83, 195
-84, 195-85, 195-86, 195-87, 195-88, 195-89, 195-9
0, 195-91, 195-92, 195-93, 195-94, 195-95, 195-96,
195-97,196-1, 196-2, 196-3, 196-4, 196-5, 196-6,
196-7, 196-8, 196-9, 196-10, 196-11, 196-12, 196-1
3, 196-14, 196-15, 196-16, 196-17, 196-18, 196-19,
196-20, 196-21, 196-22, 196-23, 196-24, 196-25, 1
96-26, 196-27, 196-28, 196-29, 196-30, 196-31, 196
-32, 196-33, 196-34, 196-35, 196-36, 196-37, 196-3
8, 196-39, 196-40, 196-41, 196-42, 196-43, 196-44,
196-45, 196-46, 196-47, 196-48, 196-49, 196-50, 1
96-51, 196-52, 196-53, 196-54, 196-55, 196-56, 196
-57, 196-58, 196-59, 196-60, 196-61, 196-62, 196-6
3, 196-64, 196-65, 196-66, 196-67, 196-68, 196-69,
196-70, 196-71, 196-72, 196-73, 196-74, 196-75, 1
96-76, 196-77, 196-78, 196-79, 196-80, 196-81, 196
-82, 196-83, 196-84, 196-85, 196-86, 196-87, 196-8
8, 196-89, 196-90, 196-91, 196-92, 196-93, 196-94,
196-95, 196-96, 196-97,197-1, 197-2, 197-3, 197-
4, 197-5, 197-6, 197-7, 197-8, 197-9, 197-10, 197-
11, 197-12, 197-13, 197-14, 197-15, 197-16, 197-1
7, 197-18, 197-19, 197-20, 197-21, 197-22, 197-23,
197-24, 197-25, 197-26, 197-27, 197-28, 197-29, 1
97-30, 197-31, 197-32, 197-33, 197-34, 197-35, 197
-36, 197-37, 197-38, 197-39, 197-40, 197-41, 197-4
2, 197-43, 197-44, 197-45, 197-46, 197-47, 197-48,
197-49, 197-50, 197-51, 197-52, 197-53, 197-54, 1
97-55, 197-56, 197-57, 197-58, 197-59, 197-60, 197
-61, 197-62, 197-63, 197-64, 197-65, 197-66, 197-6
7, 197-68, 197-69, 197-70, 197-71, 197-72, 197-73,
197-74, 197-75, 197-76, 197-77, 197-78, 197-79, 1
97-80, 197-81, 197-82, 197-83, 197-84, 197-85, 197
-86, 197-87, 197-88, 197-89, 197-90, 197-91, 197-9
2, 197-93, 197-94, 197-95, 197-96, 197-97,198-1, 1
98-2, 198-3, 198-4, 198-5, 198-6, 198-7, 198-8, 19
8-9, 198-10, 198-11, 198-12, 198-13, 198-14, 198-1
5, 198-16, 198-17, 198-18, 198-19, 198-20, 198-21,
198-22, 198-23, 198-24, 198-25, 198-26, 198-27, 1
98-28, 198-29, 198-30, 198-31, 198-32, 198-33, 198
-34, 198-35, 198-36, 198-37, 198-38, 198-39, 198-4
0, 198-41, 198-42, 198-43, 198-44, 198-45, 198-46,
198-47, 198-48, 198-49, 198-50, 198-51, 198-52, 1
98-53, 198-54, 198-55, 198-56, 198-57, 198-58, 198
-59, 198-60, 198-61, 198-62, 198-63, 198-64, 198-6
5, 198-66, 198-67, 198-68, 198-69, 198-70, 198-71,
198-72, 198-73, 198-74, 198-75, 198-76, 198-77, 1
98-78, 198-79, 198-80, 198-81, 198-82, 198-83, 198
-84, 198-85, 198-86, 198-87, 198-88, 198-89, 198-9
0, 198-91, 198-92, 198-93, 198-94, 198-95, 198-96,
198-97,199-1, 199-2, 199-3, 199-4, 199-5, 199-6,
199-7, 199-8, 199-9, 199-10, 199-11, 199-12, 199-1
3, 199-14, 199-15, 199-16, 199-17, 199-18, 199-19,
199-20, 199-21, 199-22, 199-23, 199-24, 199-25, 1
99-26, 199-27, 199-28, 199-29, 199-30, 199-31, 199
-32, 199-33, 199-34, 199-35, 199-36, 199-37, 199-3
8, 199-39, 199-40, 199-41, 199-42, 199-43, 199-44,
199-45, 199-46, 199-47, 199-48, 199-49, 199-50, 1
99-51, 199-52, 199-53, 199-54, 199-55, 199-56, 199
-57, 199-58, 199-59, 199-60, 199-61, 199-62, 199-6
3, 199-64, 199-65, 199-66, 199-67, 199-68, 199-69,
199-70, 199-71, 199-72, 199-73, 199-74, 199-75, 1
99-76, 199-77, 199-78, 199-79, 199-80, 199-81, 199
-82, 199-83, 199-84, 199-85, 199-86, 199-87, 199-8
8, 199-89, 199-90, 199-91, 199-92, 199-93, 199-94,
199-95, 199-96, 199-97,200-1, 200-2, 200-3, 200-
4, 200-5, 200-6, 200-7, 200-8, 200-9, 200-10, 200-
11, 200-12, 200-13, 200-14, 200-15, 200-16, 200-1
7, 200-18, 200-19, 200-20, 200-21, 200-22, 200-23,
200-24, 200-25, 200-26, 200-27, 200-28, 200-29, 2
00-30, 200-31, 200-32, 200-33, 200-34, 200-35, 200
-36, 200-37, 200-38, 200-39, 200-40, 200-41, 200-4
2, 200-43, 200-44, 200-45, 200-46, 200-47, 200-48,
200-49, 200-50, 200-51, 200-52, 200-53, 200-54, 2
00-55, 200-56, 200-57, 200-58, 200-59, 200-60, 200
-61, 200-62, 200-63, 200-64, 200-65, 200-66, 200-6
7, 200-68, 200-69, 200-70, 200-71, 200-72, 200-73,
200-74, 200-75, 200-76, 200-77, 200-78, 200-79, 2
00-80, 200-81, 200-82, 200-83, 200-84, 200-85, 200
-86, 200-87, 200-88, 200-89, 200-90, 200-91, 200-9
2, 200-93, 200-94, 200-95, 200-96, 200-97,201-1, 2
01-2, 201-3, 201-4, 201-5, 201-6, 201-7, 201-8, 20
1-9, 201-10, 201-11, 201-12, 201-13, 201-14, 201-1
5, 201-16, 201-17, 201-18, 201-19, 201-20, 201-21,
201-22, 201-23, 201-24, 201-25, 201-26, 201-27, 2
01-28, 201-29, 201-30, 201-31, 201-32, 201-33, 201
-34, 201-35, 201-36, 201-37, 201-38, 201-39, 201-4
0, 201-41, 201-42, 201-43, 201-44, 201-45, 201-46,
201-47, 201-48, 201-49, 201-50, 201-51, 201-52, 2
01-53, 201-54, 201-55, 201-56, 201-57, 201-58, 201
-59, 201-60, 201-61, 201-62, 201-63, 201-64, 201-6
5, 201-66, 201-67, 201-68, 201-69, 201-70, 201-71,
201-72, 201-73, 201-74, 201-75, 201-76, 201-77, 2
01-78, 201-79, 201-80, 201-81, 201-82, 201-83, 201
-84, 201-85, 201-86, 201-87, 201-88, 201-89, 201-9
0, 201-91, 201-92, 201-93, 201-94, 201-95, 201-96,
201-97,202-1, 202-2, 202-3, 202-4, 202-5, 202-6,
202-7, 202-8, 202-9, 202-10, 202-11, 202-12, 202-1
3, 202-14, 202-15, 202-16, 202-17, 202-18, 202-19,
202-20, 202-21, 202-22, 202-23, 202-24, 202-25, 2
02-26, 202-27, 202-28, 202-29, 202-30, 202-31, 202
-32, 202-33, 202-34, 202-35, 202-36, 202-37, 202-3
8, 202-39, 202-40, 202-41, 202-42, 202-43, 202-44,
202-45, 202-46, 202-47, 202-48, 202-49, 202-50, 2
02-51, 202-52, 202-53, 202-54, 202-55, 202-56, 202
-57, 202-58, 202-59, 202-60, 202-61, 202-62, 202-6
3, 202-64, 202-65, 202-66, 202-67, 202-68, 202-69,
202-70, 202-71, 202-72, 202-73, 202-74, 202-75, 2
02-76, 202-77, 202-78, 202-79, 202-80, 202-81, 202
-82, 202-83, 202-84, 202-85, 202-86, 202-87, 202-8
8, 202-89, 202-90, 202-91, 202-92, 202-93, 202-94,
202-95, 202-96, 202-97,203-1, 203-2, 203-3, 203-
4, 203-5, 203-6, 203-7, 203-8, 203-9, 203-10, 203-
11, 203-12, 203-13, 203-14, 203-15, 203-16, 203-1
7, 203-18, 203-19, 203-20, 203-21, 203-22, 203-23,
203-24, 203-25, 203-26, 203-27, 203-28, 203-29, 2
03-30, 203-31, 203-32, 203-33, 203-34, 203-35, 203
-36, 203-37, 203-38, 203-39, 203-40, 203-41, 203-4
2, 203-43, 203-44, 203-45, 203-46, 203-47, 203-48,
203-49, 203-50, 203-51, 203-52, 203-53, 203-54, 2
03-55, 203-56, 203-57, 203-58, 203-59, 203-60, 203
-61, 203-62, 203-63, 203-64, 203-65, 203-66, 203-6
7, 203-68, 203-69, 203-70, 203-71, 203-72, 203-73,
203-74, 203-75, 203-76, 203-77, 203-78, 203-79, 2
03-80, 203-81, 203-82, 203-83, 203-84, 203-85, 203
-86, 203-87, 203-88, 203-89, 203-90, 203-91, 203-9
2, 203-93, 203-94, 203-95, 203-96, 203-97,204-1, 2
04-2, 204-3, 204-4, 204-5, 204-6, 204-7, 204-8, 20
4-9, 204-10, 204-11, 204-12, 204-13, 204-14, 204-1
5, 204-16, 204-17, 204-18, 204-19, 204-20, 204-21,
204-22, 204-23, 204-24, 204-25, 204-26, 204-27, 2
04-28, 204-29, 204-30, 204-31, 204-32, 204-33, 204
-34, 204-35, 204-36, 204-37, 204-38, 204-39, 204-4
0, 204-41, 204-42, 204-43, 204-44, 204-45, 204-46,
204-47, 204-48, 204-49, 204-50, 204-51, 204-52, 2
04-53, 204-54, 204-55, 204-56, 204-57, 204-58, 204
-59, 204-60, 204-61, 204-62, 204-63, 204-64, 204-6
5, 204-66, 204-67, 204-68, 204-69, 204-70, 204-71,
204-72, 204-73, 204-74, 204-75, 204-76, 204-77, 2
04-78, 204-79, 204-80, 204-81, 204-82, 204-83, 204
-84, 204-85, 204-86, 204-87, 204-88, 204-89, 204-9
0, 204-91, 204-92, 204-93, 204-94, 204-95, 204-96,
204-97,205-1, 205-2, 205-3, 205-4, 205-5, 205-6,
205-7, 205-8, 205-9, 205-10, 205-11, 205-12, 205-1
3, 205-14, 205-15, 205-16, 205-17, 205-18, 205-19,
205-20, 205-21, 205-22, 205-23, 205-24, 205-25, 2
05-26, 205-27, 205-28, 205-29, 205-30, 205-31, 205
-32, 205-33, 205-34, 205-35, 205-36, 205-37, 205-3
8, 205-39, 205-40, 205-41, 205-42, 205-43, 205-44,
205-45, 205-46, 205-47, 205-48, 205-49, 205-50, 2
05-51, 205-52, 205-53, 205-54, 205-55, 205-56, 205
-57, 205-58, 205-59, 205-60, 205-61, 205-62, 205-6
3, 205-64, 205-65, 205-66, 205-67, 205-68, 205-69,
205-70, 205-71, 205-72, 205-73, 205-74, 205-75, 2
05-76, 205-77, 205-78, 205-79, 205-80, 205-81, 205
-82, 205-83, 205-84, 205-85, 205-86, 205-87, 205-8
8, 205-89, 205-90, 205-91, 205-92, 205-93, 205-94,
205-95, 205-96, 205-97,206-1, 206-2, 206-3, 206-
4, 206-5, 206-6, 206-7, 206-8, 206-9, 206-10, 206-
11, 206-12, 206-13, 206-14, 206-15, 206-16, 206-1
7, 206-18, 206-19, 206-20, 206-21, 206-22, 206-23,
206-24, 206-25, 206-26, 206-27, 206-28, 206-29, 2
06-30, 206-31, 206-32, 206-33, 206-34, 206-35, 206
-36, 206-37, 206-38, 206-39, 206-40, 206-41, 206-4
2, 206-43, 206-44, 206-45, 206-46, 206-47, 206-48,
206-49, 206-50, 206-51, 206-52, 206-53, 206-54, 2
06-55, 206-56, 206-57, 206-58, 206-59, 206-60, 206
-61, 206-62, 206-63, 206-64, 206-65, 206-66, 206-6
7, 206-68, 206-69, 206-70, 206-71, 206-72, 206-73,
206-74, 206-75, 206-76, 206-77, 206-78, 206-79, 2
06-80, 206-81, 206-82, 206-83, 206-84, 206-85, 206
-86, 206-87, 206-88, 206-89, 206-90, 206-91, 206-9
2, 206-93, 206-94, 206-95, 206-96, 206-97,207-1, 2
07-2, 207-3, 207-4, 207-5, 207-6, 207-7, 207-8, 20
7-9, 207-10, 207-11, 207-12, 207-13, 207-14, 207-1
5, 207-16, 207-17, 207-18, 207-19, 207-20, 207-21,
207-22, 207-23, 207-24, 207-25, 207-26, 207-27, 2
07-28, 207-29, 207-30, 207-31, 207-32, 207-33, 207
-34, 207-35, 207-36, 207-37, 207-38, 207-39, 207-4
0, 207-41, 207-42, 207-43, 207-44, 207-45, 207-46,
207-47, 207-48, 207-49, 207-50, 207-51, 207-52, 2
07-53, 207-54, 207-55, 207-56, 207-57, 207-58, 207
-59, 207-60, 207-61, 207-62, 207-63, 207-64, 207-6
5, 207-66, 207-67, 207-68, 207-69, 207-70, 207-71,
207-72, 207-73, 207-74, 207-75, 207-76, 207-77, 2
07-78, 207-79, 207-80, 207-81, 207-82, 207-83, 207
-84, 207-85, 207-86, 207-87, 207-88, 207-89, 207-9
0, 207-91, 207-92, 207-93, 207-94, 207-95, 207-96,
207-97,208-1, 208-2, 208-3, 208-4, 208-5, 208-6,
208-7, 208-8, 208-9, 208-10, 208-11, 208-12, 208-1
3, 208-14, 208-15, 208-16, 208-17, 208-18, 208-19,
208-20, 208-21, 208-22, 208-23, 208-24, 208-25, 2
08-26, 208-27, 208-28, 208-29, 208-30, 208-31, 208
-32, 208-33, 208-34, 208-35, 208-36, 208-37, 208-3
8, 208-39, 208-40, 208-41, 208-42, 208-43, 208-44,
208-45, 208-46, 208-47, 208-48, 208-49, 208-50, 2
08-51, 208-52, 208-53, 208-54, 208-55, 208-56, 208
-57, 208-58, 208-59, 208-60, 208-61, 208-62, 208-6
3, 208-64, 208-65, 208-66, 208-67, 208-68, 208-69,
208-70, 208-71, 208-72, 208-73, 208-74, 208-75, 2
08-76, 208-77, 208-78, 208-79, 208-80, 208-81, 208
-82, 208-83, 208-84, 208-85, 208-86, 208-87, 208-8
8, 208-89, 208-90, 208-91, 208-92, 208-93, 208-94,
208-95, 208-96, 208-97,209-1, 209-2, 209-3, 209-
4, 209-5, 209-6, 209-7, 209-8, 209-9, 209-10, 209-
11, 209-12, 209-13, 209-14, 209-15, 209-16, 209-1
7, 209-18, 209-19, 209-20, 209-21, 209-22, 209-23,
209-24, 209-25, 209-26, 209-27, 209-28, 209-29, 2
09-30, 209-31, 209-32, 209-33, 209-34, 209-35, 209
-36, 209-37, 209-38, 209-39, 209-40, 209-41, 209-4
2, 209-43, 209-44, 209-45, 209-46, 209-47, 209-48,
209-49, 209-50, 209-51, 209-52, 209-53, 209-54, 2
09-55, 209-56, 209-57, 209-58, 209-59, 209-60, 209
-61, 209-62, 209-63, 209-64, 209-65, 209-66, 209-6
7, 209-68, 209-69, 209-70, 209-71, 209-72, 209-73,
209-74, 209-75, 209-76, 209-77, 209-78, 209-79, 2
09-80, 209-81, 209-82, 209-83, 209-84, 209-85, 209
-86, 209-87, 209-88, 209-89, 209-90, 209-91, 209-9
2, 209-93, 209-94, 209-95, 209-96, 209-97,210-1, 2
10-2, 210-3, 210-4, 210-5, 210-6, 210-7, 210-8, 21
0-9, 210-10, 210-11, 210-12, 210-13, 210-14, 210-1
5, 210-16, 210-17, 210-18, 210-19, 210-20, 210-21,
210-22, 210-23, 210-24, 210-25, 210-26, 210-27, 2
10-28, 210-29, 210-30, 210-31, 210-32, 210-33, 210
-34, 210-35, 210-36, 210-37, 210-38, 210-39, 210-4
0, 210-41, 210-42, 210-43, 210-44, 210-45, 210-46,
210-47, 210-48, 210-49, 210-50, 210-51, 210-52, 2
10-53, 210-54, 210-55, 210-56, 210-57, 210-58, 210
-59, 210-60, 210-61, 210-62, 210-63, 210-64, 210-6
5, 210-66, 210-67, 210-68, 210-69, 210-70, 210-71,
210-72, 210-73, 210-74, 210-75, 210-76, 210-77, 2
10-78, 210-79, 210-80, 210-81, 210-82, 210-83, 210
-84, 210-85, 210-86, 210-87, 210-88, 210-89, 210-9
0, 210-91, 210-92, 210-93, 210-94, 210-95, 210-96,
210-97,211-1, 211-2, 211-3, 211-4, 211-5, 211-6,
211-7, 211-8, 211-9, 211-10, 211-11, 211-12, 211-1
3, 211-14, 211-15, 211-16, 211-17, 211-18, 211-19,
211-20, 211-21, 211-22, 211-23, 211-24, 211-25, 2
11-26, 211-27, 211-28, 211-29, 211-30, 211-31, 211
-32, 211-33, 211-34, 211-35, 211-36, 211-37, 211-3
8, 211-39, 211-40, 211-41, 211-42, 211-43, 211-44,
211-45, 211-46, 211-47, 211-48, 211-49, 211-50, 2
11-51, 211-52, 211-53, 211-54, 211-55, 211-56, 211
-57, 211-58, 211-59, 211-60, 211-61, 211-62, 211-6
3, 211-64, 211-65, 211-66, 211-67, 211-68, 211-69,
211-70, 211-71, 211-72, 211-73, 211-74, 211-75, 2
11-76, 211-77, 211-78, 211-79, 211-80, 211-81, 211
-82, 211-83, 211-84, 211-85, 211-86, 211-87, 211-8
8, 211-89, 211-90, 211-91, 211-92, 211-93, 211-94,
211-95, 211-96, 211-97,212-1, 212-2, 212-3, 212-
4, 212-5, 212-6, 212-7, 212-8, 212-9, 212-10, 212-
11, 212-12, 212-13, 212-14, 212-15, 212-16, 212-1
7, 212-18, 212-19, 212-20, 212-21, 212-22, 212-23,
212-24, 212-25, 212-26, 212-27, 212-28, 212-29, 2
12-30, 212-31, 212-32, 212-33, 212-34, 212-35, 212
-36, 212-37, 212-38, 212-39, 212-40, 212-41, 212-4
2, 212-43, 212-44, 212-45, 212-46, 212-47, 212-48,
212-49, 212-50, 212-51, 212-52, 212-53, 212-54, 2
12-55, 212-56, 212-57, 212-58, 212-59, 212-60, 212
-61, 212-62, 212-63, 212-64, 212-65, 212-66, 212-6
7, 212-68, 212-69, 212-70, 212-71, 212-72, 212-73,
212-74, 212-75, 212-76, 212-77, 212-78, 212-79, 2
12-80, 212-81, 212-82, 212-83, 212-84, 212-85, 212
-86, 212-87, 212-88, 212-89, 212-90, 212-91, 212-9
2, 212-93, 212-94, 212-95, 212-96, 212-97,213-1, 2
13-2, 213-3, 213-4, 213-5, 213-6, 213-7, 213-8, 21
3-9, 213-10, 213-11, 213-12, 213-13, 213-14, 213-1
5, 213-16, 213-17, 213-18, 213-19, 213-20, 213-21,
213-22, 213-23, 213-24, 213-25, 213-26, 213-27, 2
13-28, 213-29, 213-30, 213-31, 213-32, 213-33, 213
-34, 213-35, 213-36, 213-37, 213-38, 213-39, 213-4
0, 213-41, 213-42, 213-43, 213-44, 213-45, 213-46,
213-47, 213-48, 213-49, 213-50, 213-51, 213-52, 2
13-53, 213-54, 213-55, 213-56, 213-57, 213-58, 213
-59, 213-60, 213-61, 213-62, 213-63, 213-64, 213-6
5, 213-66, 213-67, 213-68, 213-69, 213-70, 213-71,
213-72, 213-73, 213-74, 213-75, 213-76, 213-77, 2
13-78, 213-79, 213-80, 213-81, 213-82, 213-83, 213
-84, 213-85, 213-86, 213-87, 213-88, 213-89, 213-9
0, 213-91, 213-92, 213-93, 213-94, 213-95, 213-96,
213-97,214-1, 214-2, 214-3, 214-4, 214-5, 214-6,
214-7, 214-8, 214-9, 214-10, 214-11, 214-12, 214-1
3, 214-14, 214-15, 214-16, 214-17, 214-18, 214-19,
214-20, 214-21, 214-22, 214-23, 214-24, 214-25, 2
14-26, 214-27, 214-28, 214-29, 214-30, 214-31, 214
-32, 214-33, 214-34, 214-35, 214-36, 214-37, 214-3
8, 214-39, 214-40, 214-41, 214-42, 214-43, 214-44,
214-45, 214-46, 214-47, 214-48, 214-49, 214-50, 2
14-51, 214-52, 214-53, 214-54, 214-55, 214-56, 214
-57, 214-58, 214-59, 214-60, 214-61, 214-62, 214-6
3, 214-64, 214-65, 214-66, 214-67, 214-68, 214-69,
214-70, 214-71, 214-72, 214-73, 214-74, 214-75, 2
14-76, 214-77, 214-78, 214-79, 214-80, 214-81, 214
-82, 214-83, 214-84, 214-85, 214-86, 214-87, 214-8
8, 214-89, 214-90, 214-91, 214-92, 214-93, 214-94,
214-95, 214-96, 214-97,215-1, 215-2, 215-3, 215-
4, 215-5, 215-6, 215-7, 215-8, 215-9, 215-10, 215-
11, 215-12, 215-13, 215-14, 215-15, 215-16, 215-1
7, 215-18, 215-19, 215-20, 215-21, 215-22, 215-23,
215-24, 215-25, 215-26, 215-27, 215-28, 215-29, 2
15-30, 215-31, 215-32, 215-33, 215-34, 215-35, 215
-36, 215-37, 215-38, 215-39, 215-40, 215-41, 215-4
2, 215-43, 215-44, 215-45, 215-46, 215-47, 215-48,
215-49, 215-50, 215-51, 215-52, 215-53, 215-54, 2
15-55, 215-56, 215-57, 215-58, 215-59, 215-60, 215
-61, 215-62, 215-63, 215-64, 215-65, 215-66, 215-6
7, 215-68, 215-69, 215-70, 215-71, 215-72, 215-73,
215-74, 215-75, 215-76, 215-77, 215-78, 215-79, 2
15-80, 215-81, 215-82, 215-83, 215-84, 215-85, 215
-86, 215-87, 215-88, 215-89, 215-90, 215-91, 215-9
2, 215-93, 215-94, 215-95, 215-96, 215-97,216-1, 2
16-2, 216-3, 216-4, 216-5, 216-6, 216-7, 216-8, 21
6-9, 216-10, 216-11, 216-12, 216-13, 216-14, 216-1
5, 216-16, 216-17, 216-18, 216-19, 216-20, 216-21,
216-22, 216-23, 216-24, 216-25, 216-26, 216-27, 2
16-28, 216-29, 216-30, 216-31, 216-32, 216-33, 216
-34, 216-35, 216-36, 216-37, 216-38, 216-39, 216-4
0, 216-41, 216-42, 216-43, 216-44, 216-45, 216-46,
216-47, 216-48, 216-49, 216-50, 216-51, 216-52, 2
16-53, 216-54, 216-55, 216-56, 216-57, 216-58, 216
-59, 216-60, 216-61, 216-62, 216-63, 216-64, 216-6
5, 216-66, 216-67, 216-68, 216-69, 216-70, 216-71,
216-72, 216-73, 216-74, 216-75, 216-76, 216-77, 2
16-78, 216-79, 216-80, 216-81, 216-82, 216-83, 216
-84, 216-85, 216-86, 216-87, 216-88, 216-89, 216-9
0, 216-91, 216-92, 216-93, 216-94, 216-95, 216-96,
216-97,217-1, 217-2, 217-3, 217-4, 217-5, 217-6,
217-7, 217-8, 217-9, 217-10, 217-11, 217-12, 217-1
3, 217-14, 217-15, 217-16, 217-17, 217-18, 217-19,
217-20, 217-21, 217-22, 217-23, 217-24, 217-25, 2
17-26, 217-27, 217-28, 217-29, 217-30, 217-31, 217
-32, 217-33, 217-34, 217-35, 217-36, 217-37, 217-3
8, 217-39, 217-40, 217-41, 217-42, 217-43, 217-44,
217-45, 217-46, 217-47, 217-48, 217-49, 217-50, 2
17-51, 217-52, 217-53, 217-54, 217-55, 217-56, 217
-57, 217-58, 217-59, 217-60, 217-61, 217-62, 217-6
3, 217-64, 217-65, 217-66, 217-67, 217-68, 217-69,
217-70, 217-71, 217-72, 217-73, 217-74, 217-75, 2
17-76, 217-77, 217-78, 217-79, 217-80, 217-81, 217
-82, 217-83, 217-84, 217-85, 217-86, 217-87, 217-8
8, 217-89, 217-90, 217-91, 217-92, 217-93, 217-94,
217-95, 217-96, 217-97,218-1, 218-2, 218-3, 218-
4, 218-5, 218-6, 218-7, 218-8, 218-9, 218-10, 218-
11, 218-12, 218-13, 218-14, 218-15, 218-16, 218-1
7, 218-18, 218-19, 218-20, 218-21, 218-22, 218-23,
218-24, 218-25, 218-26, 218-27, 218-28, 218-29, 2
18-30, 218-31, 218-32, 218-33, 218-34, 218-35, 218
-36, 218-37, 218-38, 218-39, 218-40, 218-41, 218-4
2, 218-43, 218-44, 218-45, 218-46, 218-47, 218-48,
218-49, 218-50, 218-51, 218-52, 218-53, 218-54, 2
18-55, 218-56, 218-57, 218-58, 218-59, 218-60, 218
-61, 218-62, 218-63, 218-64, 218-65, 218-66, 218-6
7, 218-68, 218-69, 218-70, 218-71, 218-72, 218-73,
218-74, 218-75, 218-76, 218-77, 218-78, 218-79, 2
18-80, 218-81, 218-82, 218-83, 218-84, 218-85, 218
-86, 218-87, 218-88, 218-89, 218-90, 218-91, 218-9
2, 218-93, 218-94, 218-95, 218-96, 218-97,219-1, 2
19-2, 219-3, 219-4, 219-5, 219-6, 219-7, 219-8, 21
9-9, 219-10, 219-11, 219-12, 219-13, 219-14, 219-1
5, 219-16, 219-17, 219-18, 219-19, 219-20, 219-21,
219-22, 219-23, 219-24, 219-25, 219-26, 219-27, 2
19-28, 219-29, 219-30, 219-31, 219-32, 219-33, 219
-34, 219-35, 219-36, 219-37, 219-38, 219-39, 219-4
0, 219-41, 219-42, 219-43, 219-44, 219-45, 219-46,
219-47, 219-48, 219-49, 219-50, 219-51, 219-52, 2
19-53, 219-54, 219-55, 219-56, 219-57, 219-58, 219
-59, 219-60, 219-61, 219-62, 219-63, 219-64, 219-6
5, 219-66, 219-67, 219-68, 219-69, 219-70, 219-71,
219-72, 219-73, 219-74, 219-75, 219-76, 219-77, 2
19-78, 219-79, 219-80, 219-81, 219-82, 219-83, 219
-84, 219-85, 219-86, 219-87, 219-88, 219-89, 219-9
0, 219-91, 219-92, 219-93, 219-94, 219-95, 219-96,
219-97,220-1, 220-2, 220-3, 220-4, 220-5, 220-6,
220-7, 220-8, 220-9, 220-10, 220-11, 220-12, 220-1
3, 220-14, 220-15, 220-16, 220-17, 220-18, 220-19,
220-20, 220-21, 220-22, 220-23, 220-24, 220-25, 2
20-26, 220-27, 220-28, 220-29, 220-30, 220-31, 220
-32, 220-33, 220-34, 220-35, 220-36, 220-37, 220-3
8, 220-39, 220-40, 220-41, 220-42, 220-43, 220-44,
220-45, 220-46, 220-47, 220-48, 220-49, 220-50, 2
20-51, 220-52, 220-53, 220-54, 220-55, 220-56, 220
-57, 220-58, 220-59, 220-60, 220-61, 220-62, 220-6
3, 220-64, 220-65, 220-66, 220-67, 220-68, 220-69,
220-70, 220-71, 220-72, 220-73, 220-74, 220-75, 2
20-76, 220-77, 220-78, 220-79, 220-80, 220-81, 220
-82, 220-83, 220-84, 220-85, 220-86, 220-87, 220-8
8, 220-89, 220-90, 220-91, 220-92, 220-93, 220-94,
220-95, 220-96, 220-97,221-1, 221-2, 221-3, 221-
4, 221-5, 221-6, 221-7, 221-8, 221-9, 221-10, 221-
11, 221-12, 221-13, 221-14, 221-15, 221-16, 221-1
7, 221-18, 221-19, 221-20, 221-21, 221-22, 221-23,
221-24, 221-25, 221-26, 221-27, 221-28, 221-29, 2
21-30, 221-31, 221-32, 221-33, 221-34, 221-35, 221
-36, 221-37, 221-38, 221-39, 221-40, 221-41, 221-4
2, 221-43, 221-44, 221-45, 221-46, 221-47, 221-48,
221-49, 221-50, 221-51, 221-52, 221-53, 221-54, 2
21-55, 221-56, 221-57, 221-58, 221-59, 221-60, 221
-61, 221-62, 221-63, 221-64, 221-65, 221-66, 221-6
7, 221-68, 221-69, 221-70, 221-71, 221-72, 221-73,
221-74, 221-75, 221-76, 221-77, 221-78, 221-79, 2
21-80, 221-81, 221-82, 221-83, 221-84, 221-85, 221
-86, 221-87, 221-88, 221-89, 221-90, 221-91, 221-9
2, 221-93, 221-94, 221-95, 221-96, 221-97,222-1, 2
22-2, 222-3, 222-4, 222-5, 222-6, 222-7, 222-8, 22
2-9, 222-10, 222-11, 222-12, 222-13, 222-14, 222-1
5, 222-16, 222-17, 222-18, 222-19, 222-20, 222-21,
222-22, 222-23, 222-24, 222-25, 222-26, 222-27, 2
22-28, 222-29, 222-30, 222-31, 222-32, 222-33, 222
-34, 222-35, 222-36, 222-37, 222-38, 222-39, 222-4
0, 222-41, 222-42, 222-43, 222-44, 222-45, 222-46,
222-47, 222-48, 222-49, 222-50, 222-51, 222-52, 2
22-53, 222-54, 222-55, 222-56, 222-57, 222-58, 222
-59, 222-60, 222-61, 222-62, 222-63, 222-64, 222-6
5, 222-66, 222-67, 222-68, 222-69, 222-70, 222-71,
222-72, 222-73, 222-74, 222-75, 222-76, 222-77, 2
22-78, 222-79, 222-80, 222-81, 222-82, 222-83, 222
-84, 222-85, 222-86, 222-87, 222-88, 222-89, 222-9
0, 222-91, 222-92, 222-93, 222-94, 222-95, 222-96,
222-97,223-1, 223-2, 223-3, 223-4, 223-5, 223-6,
223-7, 223-8, 223-9, 223-10, 223-11, 223-12, 223-1
3, 223-14, 223-15, 223-16, 223-17, 223-18, 223-19,
223-20, 223-21, 223-22, 223-23, 223-24, 223-25, 2
23-26, 223-27, 223-28, 223-29, 223-30, 223-31, 223
-32, 223-33, 223-34, 223-35, 223-36, 223-37, 223-3
8, 223-39, 223-40, 223-41, 223-42, 223-43, 223-44,
223-45, 223-46, 223-47, 223-48, 223-49, 223-50, 2
23-51, 223-52, 223-53, 223-54, 223-55, 223-56, 223
-57, 223-58, 223-59, 223-60, 223-61, 223-62, 223-6
3, 223-64, 223-65, 223-66, 223-67, 223-68, 223-69,
223-70, 223-71, 223-72, 223-73, 223-74, 223-75, 2
23-76, 223-77, 223-78, 223-79, 223-80, 223-81, 223
-82, 223-83, 223-84, 223-85, 223-86, 223-87, 223-8
8, 223-89, 223-90, 223-91, 223-92, 223-93, 223-94,
223-95, 223-96, 223-97,224-1, 224-2, 224-3, 224-
4, 224-5, 224-6, 224-7, 224-8, 224-9, 224-10, 224-
11, 224-12, 224-13, 224-14, 224-15, 224-16, 224-1
7, 224-18, 224-19, 224-20, 224-21, 224-22, 224-23,
224-24, 224-25, 224-26, 224-27, 224-28, 224-29, 2
24-30, 224-31, 224-32, 224-33, 224-34, 224-35, 224
-36, 224-37, 224-38, 224-39, 224-40, 224-41, 224-4
2, 224-43, 224-44, 224-45, 224-46, 224-47, 224-48,
224-49, 224-50, 224-51, 224-52, 224-53, 224-54, 2
24-55, 224-56, 224-57, 224-58, 224-59, 224-60, 224
-61, 224-62, 224-63, 224-64, 224-65, 224-66, 224-6
7, 224-68, 224-69, 224-70, 224-71, 224-72, 224-73,
224-74, 224-75, 224-76, 224-77, 224-78, 224-79, 2
24-80, 224-81, 224-82, 224-83, 224-84, 224-85, 224
-86, 224-87, 224-88, 224-89, 224-90, 224-91, 224-9
2, 224-93, 224-94, 224-95, 224-96, 224-97,225-1, 2
25-2, 225-3, 225-4, 225-5, 225-6, 225-7, 225-8, 22
5-9, 225-10, 225-11, 225-12, 225-13, 225-14, 225-1
5, 225-16, 225-17, 225-18, 225-19, 225-20, 225-21,
225-22, 225-23, 225-24, 225-25, 225-26, 225-27, 2
25-28, 225-29, 225-30, 225-31, 225-32, 225-33, 225
-34, 225-35, 225-36, 225-37, 225-38, 225-39, 225-4
0, 225-41, 225-42, 225-43, 225-44, 225-45, 225-46,
225-47, 225-48, 225-49, 225-50, 225-51, 225-52, 2
25-53, 225-54, 225-55, 225-56, 225-57, 225-58, 225
-59, 225-60, 225-61, 225-62, 225-63, 225-64, 225-6
5, 225-66, 225-67, 225-68, 225-69, 225-70, 225-71,
225-72, 225-73, 225-74, 225-75, 225-76, 225-77, 2
25-78, 225-79, 225-80, 225-81, 225-82, 225-83, 225
-84, 225-85, 225-86, 225-87, 225-88, 225-89, 225-9
0, 225-91, 225-92, 225-93, 225-94, 225-95, 225-96,
225-97,226-1, 226-2, 226-3, 226-4, 226-5, 226-6,
226-7, 226-8, 226-9, 226-10, 226-11, 226-12, 226-1
3, 226-14, 226-15, 226-16, 226-17, 226-18, 226-19,
226-20, 226-21, 226-22, 226-23, 226-24, 226-25, 2
26-26, 226-27, 226-28, 226-29, 226-30, 226-31, 226
-32, 226-33, 226-34, 226-35, 226-36, 226-37, 226-3
8, 226-39, 226-40, 226-41, 226-42, 226-43, 226-44,
226-45, 226-46, 226-47, 226-48, 226-49, 226-50, 2
26-51, 226-52, 226-53, 226-54, 226-55, 226-56, 226
-57, 226-58, 226-59, 226-60, 226-61, 226-62, 226-6
3, 226-64, 226-65, 226-66, 226-67, 226-68, 226-69,
226-70, 226-71, 226-72, 226-73, 226-74, 226-75, 2
26-76, 226-77, 226-78, 226-79, 226-80, 226-81, 226
-82, 226-83, 226-84, 226-85, 226-86, 226-87, 226-8
8, 226-89, 226-90, 226-91, 226-92, 226-93, 226-94,
226-95, 226-96, 226-97,227-1, 227-2, 227-3, 227-
4, 227-5, 227-6, 227-7, 227-8, 227-9, 227-10, 227-
11, 227-12, 227-13, 227-14, 227-15, 227-16, 227-1
7, 227-18, 227-19, 227-20, 227-21, 227-22, 227-23,
227-24, 227-25, 227-26, 227-27, 227-28, 227-29, 2
27-30, 227-31, 227-32, 227-33, 227-34, 227-35, 227
-36, 227-37, 227-38, 227-39, 227-40, 227-41, 227-4
2, 227-43, 227-44, 227-45, 227-46, 227-47, 227-48,
227-49, 227-50, 227-51, 227-52, 227-53, 227-54, 2
27-55, 227-56, 227-57, 227-58, 227-59, 227-60, 227
-61, 227-62, 227-63, 227-64, 227-65, 227-66, 227-6
7, 227-68, 227-69, 227-70, 227-71, 227-72, 227-73,
227-74, 227-75, 227-76, 227-77, 227-78, 227-79, 2
27-80, 227-81, 227-82, 227-83, 227-84, 227-85, 227
-86, 227-87, 227-88, 227-89, 227-90, 227-91, 227-9
2, 227-93, 227-94, 227-95, 227-96, 227-97,228-1, 2
28-2, 228-3, 228-4, 228-5, 228-6, 228-7, 228-8, 22
8-9, 228-10, 228-11, 228-12, 228-13, 228-14, 228-1
5, 228-16, 228-17, 228-18, 228-19, 228-20, 228-21,
228-22, 228-23, 228-24, 228-25, 228-26, 228-27, 2
28-28, 228-29, 228-30, 228-31, 228-32, 228-33, 228
-34, 228-35, 228-36, 228-37, 228-38, 228-39, 228-4
0, 228-41, 228-42, 228-43, 228-44, 228-45, 228-46,
228-47, 228-48, 228-49, 228-50, 228-51, 228-52, 2
28-53, 228-54, 228-55, 228-56, 228-57, 228-58, 228
-59, 228-60, 228-61, 228-62, 228-63, 228-64, 228-6
5, 228-66, 228-67, 228-68, 228-69, 228-70, 228-71,
228-72, 228-73, 228-74, 228-75, 228-76, 228-77, 2
28-78, 228-79, 228-80, 228-81, 228-82, 228-83, 228
-84, 228-85, 228-86, 228-87, 228-88, 228-89, 228-9
0, 228-91, 228-92, 228-93, 228-94, 228-95, 228-96,
228-97,229-1, 229-2, 229-3, 229-4, 229-5, 229-6,
229-7, 229-8, 229-9, 229-10, 229-11, 229-12, 229-1
3, 229-14, 229-15, 229-16, 229-17, 229-18, 229-19,
229-20, 229-21, 229-22, 229-23, 229-24, 229-25, 2
29-26, 229-27, 229-28, 229-29, 229-30, 229-31, 229
-32, 229-33, 229-34, 229-35, 229-36, 229-37, 229-3
8, 229-39, 229-40, 229-41, 229-42, 229-43, 229-44,
229-45, 229-46, 229-47, 229-48, 229-49, 229-50, 2
29-51, 229-52, 229-53, 229-54, 229-55, 229-56, 229
-57, 229-58, 229-59, 229-60, 229-61, 229-62, 229-6
3, 229-64, 229-65, 229-66, 229-67, 229-68, 229-69,
229-70, 229-71, 229-72, 229-73, 229-74, 229-75, 2
29-76, 229-77, 229-78, 229-79, 229-80, 229-81, 229
-82, 229-83, 229-84, 229-85, 229-86, 229-87, 229-8
8, 229-89, 229-90, 229-91, 229-92, 229-93, 229-94,
229-95, 229-96, 229-97,230-1, 230-2, 230-3, 230-
4, 230-5, 230-6, 230-7, 230-8, 230-9, 230-10, 230-
11, 230-12, 230-13, 230-14, 230-15, 230-16, 230-1
7, 230-18, 230-19, 230-20, 230-21, 230-22, 230-23,
230-24, 230-25, 230-26, 230-27, 230-28, 230-29, 2
30-30, 230-31, 230-32, 230-33, 230-34, 230-35, 230
-36, 230-37, 230-38, 230-39, 230-40, 230-41, 230-4
2, 230-43, 230-44, 230-45, 230-46, 230-47, 230-48,
230-49, 230-50, 230-51, 230-52, 230-53, 230-54, 2
30-55, 230-56, 230-57, 230-58, 230-59, 230-60, 230
-61, 230-62, 230-63, 230-64, 230-65, 230-66, 230-6
7, 230-68, 230-69, 230-70, 230-71, 230-72, 230-73,
230-74, 230-75, 230-76, 230-77, 230-78, 230-79, 2
30-80, 230-81, 230-82, 230-83, 230-84, 230-85, 230
-86, 230-87, 230-88, 230-89, 230-90, 230-91, 230-9
2, 230-93, 230-94, 230-95, 230-96, 230-97,231-1, 2
31-2, 231-3, 231-4, 231-5, 231-6, 231-7, 231-8, 23
1-9, 231-10, 231-11, 231-12, 231-13, 231-14, 231-1
5, 231-16, 231-17, 231-18, 231-19, 231-20, 231-21,
231-22, 231-23, 231-24, 231-25, 231-26, 231-27, 2
31-28, 231-29, 231-30, 231-31, 231-32, 231-33, 231
-34, 231-35, 231-36, 231-37, 231-38, 231-39, 231-4
0, 231-41, 231-42, 231-43, 231-44, 231-45, 231-46,
231-47, 231-48, 231-49, 231-50, 231-51, 231-52, 2
31-53, 231-54, 231-55, 231-56, 231-57, 231-58, 231
-59, 231-60, 231-61, 231-62, 231-63, 231-64, 231-6
5, 231-66, 231-67, 231-68, 231-69, 231-70, 231-71,
231-72, 231-73, 231-74, 231-75, 231-76, 231-77, 2
31-78, 231-79, 231-80, 231-81, 231-82, 231-83, 231
-84, 231-85, 231-86, 231-87, 231-88, 231-89, 231-9
0, 231-91, 231-92, 231-93, 231-94, 231-95, 231-96,
231-97,232-1, 232-2, 232-3, 232-4, 232-5, 232-6,
232-7, 232-8, 232-9, 232-10, 232-11, 232-12, 232-1
3, 232-14, 232-15, 232-16, 232-17, 232-18, 232-19,
232-20, 232-21, 232-22, 232-23, 232-24, 232-25, 2
32-26, 232-27, 232-28, 232-29, 232-30, 232-31, 232
-32, 232-33, 232-34, 232-35, 232-36, 232-37, 232-3
8, 232-39, 232-40, 232-41, 232-42, 232-43, 232-44,
232-45, 232-46, 232-47, 232-48, 232-49, 232-50, 2
32-51, 232-52, 232-53, 232-54, 232-55, 232-56, 232
-57, 232-58, 232-59, 232-60, 232-61, 232-62, 232-6
3, 232-64, 232-65, 232-66, 232-67, 232-68, 232-69,
232-70, 232-71, 232-72, 232-73, 232-74, 232-75, 2
32-76, 232-77, 232-78, 232-79, 232-80, 232-81, 232
-82, 232-83, 232-84, 232-85, 232-86, 232-87, 232-8
8, 232-89, 232-90, 232-91, 232-92, 232-93, 232-94,
232-95, 232-96, 232-97,233-1, 233-2, 233-3, 233-
4, 233-5, 233-6, 233-7, 233-8, 233-9, 233-10, 233-
11, 233-12, 233-13, 233-14, 233-15, 233-16, 233-1
7, 233-18, 233-19, 233-20, 233-21, 233-22, 233-23,
233-24, 233-25, 233-26, 233-27, 233-28, 233-29, 2
33-30, 233-31, 233-32, 233-33, 233-34, 233-35, 233
-36, 233-37, 233-38, 233-39, 233-40, 233-41, 233-4
2, 233-43, 233-44, 233-45, 233-46, 233-47, 233-48,
233-49, 233-50, 233-51, 233-52, 233-53, 233-54, 2
33-55, 233-56, 233-57, 233-58, 233-59, 233-60, 233
-61, 233-62, 233-63, 233-64, 233-65, 233-66, 233-6
7, 233-68, 233-69, 233-70, 233-71, 233-72, 233-73,
233-74, 233-75, 233-76, 233-77, 233-78, 233-79, 2
33-80, 233-81, 233-82, 233-83, 233-84, 233-85, 233
-86, 233-87, 233-88, 233-89, 233-90, 233-91, 233-9
2, 233-93, 233-94, 233-95, 233-96, 233-97,234-1, 2
34-2, 234-3, 234-4, 234-5, 234-6, 234-7, 234-8, 23
4-9, 234-10, 234-11, 234-12, 234-13, 234-14, 234-1
5, 234-16, 234-17, 234-18, 234-19, 234-20, 234-21,
234-22, 234-23, 234-24, 234-25, 234-26, 234-27, 2
34-28, 234-29, 234-30, 234-31, 234-32, 234-33, 234
-34, 234-35, 234-36, 234-37, 234-38, 234-39, 234-4
0, 234-41, 234-42, 234-43, 234-44, 234-45, 234-46,
234-47, 234-48, 234-49, 234-50, 234-51, 234-52, 2
34-53, 234-54, 234-55, 234-56, 234-57, 234-58, 234
-59, 234-60, 234-61, 234-62, 234-63, 234-64, 234-6
5, 234-66, 234-67, 234-68, 234-69, 234-70, 234-71,
234-72, 234-73, 234-74, 234-75, 234-76, 234-77, 2
34-78, 234-79, 234-80, 234-81, 234-82, 234-83, 234
-84, 234-85, 234-86, 234-87, 234-88, 234-89, 234-9
0, 234-91, 234-92, 234-93, 234-94, 234-95, 234-96,
234-97.

Among the combinations in Table 1, the preferred ones are 1, 2, 3, 4, 5, 6, 7, 8, 9, 31, 3
4, 35, 36, 76, 77, 78, 106, 107,
108, 136, 137, 138, 163 and 199, more preferably 1, 163 and 199;
Among the combinations in Table 2 above, preferred ones are 1 to 8, 32 to 53 and 87 to 97, and more preferred are 1, 38, 39, 40, 41 and 42.

Of the compounds represented by the combination of groups selected from Tables 1 and 2, the preferred one is
-1,1-2,1-3,1-4,1-5,1-6,1-
7, 1-8, 1-32, 1-33, 1-34, 1-3
5, 1-36, 1-37, 1-38, 1-39, 1-4
0, 1-41, 1-42, 1-43, 1-44, 1-4
5,1-48,1-49,1-50,1-51,1-5
2,1-53,7-1,7-2,7-3,7-4,7-
5,7-6,7-7,7-8,7-32,7-33,7
-34,7-35,7-36,7-37,7-38,7
-39,7-40,7-41,7-42,7-43,7
-44, 7-45, 7-48, 7-49, 7-50, 7
-51, 7-52, 7-53, 163-1, 163-3
6, 163-38, 163-39, 163-40, 16
3-41, 163-42, 199-1, 199-38,
199-39, 199-40, 199-41 and 199
-42, and more preferably, 5-acetamido-4-guanidino-2,3,4,5,7-pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid. (1-1), 5-acetamide-
4-guanidino-9-O-dodecanoyl-2,3,4,
5,7-Pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid (1-4
0), 5-acetamido-4-guanidino-9-O-myristoyl-2,3,4,5,7-pentadeoxy-7-
Fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid (1-41), 5-acetamido-4-guanidino-9-O-hexadecanoyl-2,3,4,
5,7-Pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid (1-4
2), 5-acetamide-4-guanidino-2,3,4,
5,7-Pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopyranosonic acid (163
-1), 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadeoxy-7
-Methoxy-D-glycero-D-galacto-non-2-
Enopyranosonic acid (163-38), 5-acetamide-
4-guanidino-9-O-decanoyl-2,3,4
5,7-Pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopyranosonic acid (163
-39), 5-acetamide-4-guanidino-9-O-
Dodecanoyl-2,3,4,5,7-pentadeoxy-
7-methoxy-D-glycero-D-galacto-non-2
-Enopyranosonic acid (163-40), 5-acetamido-4-guanidino-9-O-myristoyl-2,3,
4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopyranosonic acid (1
63-41), 5-acetamido-4-guanidino-9-
O-hexadecanoyl-2,3,4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-
Non-2-enopyranosonic acid (163-42), 5-acetamido-4-guanidino-2,3,4,5,7-pentadeoxy-7-ethoxy-D-glycero-D-galacto-non-2-enopyranosone Acid (199-1), 5-
Acetamide-4-guanidino-9-O-octanoyl-
2,3,4,5,7-pentadeoxy-7-ethoxy-
D-glycero-D-galacto-non-2-enopyranosonic acid (199-38), 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadeoxy-7-ethoxy -D-glycero-D-galacto-non-2-enopyranosonic acid (199-40), 5
-Acetamido-4-guanidino-9-O-myristoyl-2,3,4,5,7-pentadeoxy-7-ethoxy-D-glycero-D-galacto-non-2-enopyranosonic acid (199-41) and 5-acetamido-4-guanidino-9-O-palmitoyl-2,3,4,5,7-
Pentadeoxy-7-ethoxy-D-glycero-D-galacto-non-2-enopyranosonic acid (199-42)
Is raised.

[0026]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a method for producing compound (1) which is an active ingredient of the present invention will be described.

The compound (1) which is an active ingredient of the present invention comprises
It can be produced by the method described in the method A, B or C shown below.

The starting compound (2) used in the methods A and B can be produced by the method described in the following method D, method E, method F or method G.

Further, the starting compound (5) used in Method C
Can be produced by the method described in the following Method H.

[0030] R ¹ , R ² ,
R ^2a , R ^2b , R ³ , R ^3a , R ⁴ , R ⁵ , R ^5a , R ⁶ , R
^{7, R 8, W, W} a, X, X a, X b, X c, Y, Z,
The meanings of Me, Ac, Boc and Bn are as follows.

That is, R ¹ , R ² , R ³ , X, Y and Z have the same meanings as described above, and R ^2a has the same meaning as R ² described above or a hydroxyl-protecting group (preferably Represents a t-butyldimethylsilyl group); R ^2b represents a hydroxyl-protecting group (preferably a t-butyldimethylsilyl group);
^3a the above R ³ whether or hydroxyl-protecting group the same meanings (preferably, t- butyl dimethylsilyl group) indicates, R
⁴ represents a halogen atom, an acetyloxy group or an alkoxy group having 1 to 4 carbon atoms, R ⁵ represents a halogen atom, a hydroxyl group or an alkoxy group having 1 to 4 carbon atoms, R ^5a represents a hydroxyl group, and R ^{6 represents} , R ⁷ and R ⁸ are the same or different 2 to carbon atoms with 25 aliphatic acyl group, W is a group that produces a hydrogen atom or an ester, W ^a is the aforementioned W
Or a carboxyl-protecting group (preferably, allyl, methoxymethyl, methylthiomethyl, 2-
(Trimethylsilyl) ethoxy methoxy or diphenylmethyl group, more preferably represents a a a) diphenylmethyl group, X ^a is the hydroxyl group which is or protecting the same meanings as defined above for X (preferably, t- butyl ^Xb represents a halogen atom, an aliphatic acyloxy group having 2 to 25 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, and ^Xc represents an alkoxy group having 1 to 4 carbon atoms. , Ac represents an acetyl group, Bn represents a benzyl group, Boc represents a t-butoxycarbonyl group, and Me represents a methyl group.

Hereinafter, each method will be described in detail.

(Method A)

[0034]

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Method A is to remove the protecting group of a compound obtained by reacting N, N'-di-tert-butoxycarbonylthiourea with a starting compound (2) which can be easily obtained by the method described below. Is a method for producing a compound (1a) which is an active ingredient of the present invention.

(Step A-1) This step is carried out in an inert solvent
Compound (2) is added with N, in the presence of a base and mercuric chloride.
In this step, the compound (3) is produced by reacting N′-di-t-butoxycarbonylthiourea.

As the solvent to be used, aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; Amides such as N, N-dimethylacetamide and dimethylformamide are exemplified, and amides (particularly N, N-dimethylacetamide and dimethylformamide) are preferred.

As the base used, organic bases such as triethylamine and dimethylaminopyridine are preferred.

The reaction temperature is usually from -10 to 50 ° C, preferably from 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
Hours to 24 hours, preferably 5 to 10 hours.

After completion of the reaction, for example, the reaction solution is filtered under reduced pressure to remove insolubles, an immiscible organic solvent such as water and ethyl acetate is added, and after washing with water, the organic layer containing the target compound is separated. After drying over anhydrous magnesium sulfate or the like, it is obtained by distilling off the solvent. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Step A-2) In this step, compound (3) is prepared in an inert solvent.
Is reacted with a reagent for removing the tert-butoxycarbonyl group, to give compound (1a) which is an active ingredient of the present invention.
This is the step of manufacturing.

The solvent used is preferably an alcohol such as methanol or ethanol, water or a mixed solvent thereof.

The reagent used for the removal is preferably an acid, and the acid is not particularly limited as long as it can be used as an acid catalyst in a usual reaction, but hydrochloric acid, hydrobromic acid, sulfuric acid, Inorganic acids such as perchloric acid, phosphoric acid or Bronsted acids such as acetic acid, formic acid, oxalic acid, organic acids such as methanesulfonic acid, paratoluenesulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid or zinc chloride, tetrachloride Examples include Lewis acids such as tin, boron trichloride, boron trifluoride, and boron tribromide, or acidic ion exchange resins, and are preferably organic acids (particularly acetic acid and trifluoroacetic acid).

The reaction temperature is usually from -10 to 50 ° C, preferably from 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the target product can be obtained by neutralizing the reaction solution and distilling off the solvent under reduced pressure and purifying the residue obtained by silica gel chromatography. Note that whether R ^2a or R ^3a is a hydroxyl-protecting group,
^{When a} is a protected hydroxyl group or Wa is ^a carboxyl-protecting group, the compound which is the active ingredient of the present invention can be obtained by further removing them.

The method for removing the protecting group varies depending on the type of the protecting group, and is usually used, for example, Protective Group
s in Organic Synthesis, Second Edition (1991, Gr
een etc.).

When the protecting group for the hydroxyl group is a trialkylsilyl group such as a tert-butyldimethylsilyl group, acetic acid in a mixture of water and tetrahydrofuran is preferably used, or tetrabutylammonium fluoride in tetrahydrofuran is used. Used.

When the protecting group of the carboxylic acid is a diphenylmethyl group, catalytic reduction is performed, an acid such as acetic acid or trifluoroacetic acid is used, or a trifluoroborane-diethyl ether complex is used.

(Method B)

[0049]

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In the method B, a starting material compound (2), which can be easily obtained by a method described later, is reacted with ammonia or a hydroxyamine in which an amino moiety may be substituted by an alkyl group having 1 to 4 carbon atoms, Further, the method is a method for producing a compound (1) which is an active ingredient of the present invention by removing a protecting group, if desired.

(Step B-1) This step is carried out in an inert solvent
The compound (2) is reacted with a cyanating agent to give a compound (4)
This is the step of manufacturing.

Examples of the solvent used include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol. , Alcohols such as glycerin, octanol, cyclohexanol and methyl cellosolve; formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidinone, hexamethylphospho Amides such as rotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane, and preferably alcohols (particularly methanol).

As the cyanating agent to be used, cyanogen bromide is preferable, and sodium acetate is used simultaneously as a base.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 40 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the residue obtained by distilling off the solvent is purified by recrystallization, silica gel chromatography or the like to obtain the desired product. (Step B-2) In this step, compound (4) is prepared in an inert solvent.
This is a step of producing a compound (1), which is an active ingredient of the present invention, by reacting ammonia or a hydroxyamine in which an amino moiety may be substituted with an alkyl group having 1 to 4 carbon atoms.

As the solvent used, alcohols (particularly methanol) are preferred.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 40 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the residue obtained by distilling off the solvent is purified by recrystallization, silica gel chromatography or the like to obtain the desired product. Note that R ^2a
Or, when R ^3a is a protecting group for a hydroxyl group, X ^a is a protected hydroxyl group, or when Wa is a protecting group for ^a carboxyl group, they are further removed as in Method A. Thereby, the compound which is the active ingredient of the present invention is obtained.

(Method C)

[0060]

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In the method C, a compound (1c) which is an active ingredient of the present invention is produced by removing a protecting group of a compound obtained by acylating a raw material compound (5) which can be easily obtained by a method described later. How to

(Step C-1) This step is carried out in an inert solvent
In this step, a desired acyl group is introduced into compound (5) to produce compound (6).

The following acylation methods are available.

<Method 1> A compound having the general formula RCO-Hal or a compound having the general formula RCO-O-COR [wherein R represents an alkyl group and Hal represents a leaving group. Such a leaving group is not particularly limited as long as it is a group that usually leaves as a nucleophilic residue, but is preferably chlorine,
Halogen atoms such as bromine and iodine; lower alkoxycarbonyloxy groups such as methoxycarbonyloxy and ethoxycarbonyloxy; halogenated alkylcarbonyloxy groups such as chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy and trifluoroacetyloxy Lower alkanesulfonyloxy groups such as methanesulfonyloxy and ethanesulfonyloxy; halogeno lower alkanesulfonyloxy groups such as trifluoromethanesulfonyloxy and pentafluoroethanesulfonyloxy; benzenesulfonyloxy;
Examples include arylsulfonyloxy groups such as p-toluenesulfonyloxy and p-nitrobenzenesulfonyloxy, and more preferably a halogen atom, a halogeno lower alkanesulfonyloxy group, and an arylsulfonyloxy group. is there. And compound (5)
A method of reacting in a solvent in the presence or absence of a base.

<Method 2> Compound having the general formula RCOOH wherein R has the same meaning as described above. And compound (5) in a solvent in the presence or absence of an "esterifying agent" and a catalytic amount of a base.

Examples of the "esterifying agent" to be used include a condensing agent; halogenated formate such as methyl chloroformate and ethyl chloroformate; and cyanophosphate diester such as diethyl cyanophosphate. Examples of the "condensing agent" include N-hydroxysuccinimide,
1-hydroxybenzotriazole, N-hydroxy-
N-hydroxy derivatives such as 5-norbornene-2,3-dicarboximide; disulfide compounds such as 2,2'-dipyridyl disulfide; N, N'-
Succinic compounds such as dissuccinimidyl carbonate; phosphinic chloride compounds such as N, N'-bis (2-oxo-3-oxazolidinyl) phosphinic chloride; N, N'-disuccin Imidyl oxalate (DSO), N, N'-diphthalimide oxalate (DPO), N, N'-bis (norbornenylsuccinimidyl) oxalate (BNO), 1,
1'-bis (benzotriazolyl) oxalate (BB
TO), 1,1'-bis (6-chlorobenzotriazolyl) oxalate (BCTO), 1,1'-bis (6-
Oxalate derivatives such as trifluoromethylbenzotriazolyl) oxalate (BTBO); triarylphosphines such as triphenylphosphine; N-ethyl-, such as triarylphosphines;
N-lower alkyl-5-arylisoxazolium-3'-sulfonates such as 5-phenylisoxazolium-3'-sulfonate; N 'such as N', N'-dicyclohexylcarbodiimide (DCC) , N '
-Dicycloalkylcarbodiimides, 1-ethyl-3
-(3-dimethylaminopropyl) carbodiimide (E
Carbodiimide derivatives such as DAPC); diheteroaryl diselenides such as di-2-pyridyl diselenide;
arylsulfonyltriazolides such as p-nitrobenzenesulfonyltriazolide; 2-halo-1- such as 2-chloro-1-methylpyridinium iodide
Lower alkylpyridinium halides; diarylphosphoryl azides such as diphenylphosphoryl azide (DPPA); 1,1'-oxalyldiimidazole,
Imidazole derivatives such as N, N'-carbonyldiimidazole; 1-hydroxybenzotriazole (HO
A benzotriazole derivative such as BT); a dicarboximide derivative such as N-hydroxy-5-norbornene-2,3-dicarboximide (HONB), and preferably a diarylphosphoryl azide. is there.

<Method 3> Compound having the general formula RCOOH wherein R is as defined above. And compound (5) in a solvent in the presence of a halogenated dialkyl ester of a phosphoric acid such as diethyl chloride and a base,
How to react.

The method is performed according to any of the above methods.

The solvent used in <Method 1> is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane or heptane. Hydrogens: benzene, toluene,
Aromatic hydrocarbons such as xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate Esters; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ethers; acetonitrile, isobutyronitrile; nitriles; formamide, N, N-dimethylformamide, N, N- Dimethylacetamide, N-methyl-2-pyrrolidone, N-
Amides such as methylpyrrolidinone and hexamethylphosphorotriamide can be mentioned. The base used in <Method 1> is not particularly limited as long as it is used as a base in a normal reaction.
Preferably, N-methylmorpholine, triethylamine,
Tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N
Organic bases such as -dimethylamino) pyridine, 2,6-di (tert-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline and N, N-diethylaniline. In addition, 4- (N, N-dimethylamino) pyridine and 4-pyrrolidinopyridine can be used in a catalytic amount in combination with other bases.
In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride, dibenzo-18-
Crown ethers such as crown-6 can also be added. The reaction temperature is usually from -20 ° C to the reflux temperature of the solvent used, preferably from 0 ° C to the reflux temperature of the solvent used. The reaction time varies depending mainly on the reaction temperature, the starting compound, the type of the base used or the type of the solvent used, but is usually from 10 minutes to 3 days, preferably from 1 hour to 6 hours.

The solvent used in <Method 2> is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane or heptane. Hydrogens: benzene, toluene,
Aromatic hydrocarbons such as xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate Esters; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ethers; acetonitrile, isobutyronitrile; nitriles; formamide, N, N-dimethylformamide, N, N- Dimethylacetamide, N-methyl-2-pyrrolidone, N-
Amides such as methylpyrrolidinone and hexamethylphosphorotriamide can be mentioned. As the base used in <Method 2>, the same base as described in <Method 1> can be used. The reaction is carried out at a temperature of -20 ° C to 80 ° C, preferably 0 ° C to room temperature. The reaction time mainly depends on the reaction temperature,
Although it depends on the type of the starting compound, the reaction reagent or the solvent used, it is usually 10 minutes to 3 days, preferably
30 minutes to 1 day.

The solvent used in <Method 3> is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane or heptane. Hydrogens: benzene, toluene,
Aromatic hydrocarbons such as xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate Esters; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ethers; acetonitrile, isobutyronitrile; nitriles; formamide, N, N-dimethylformamide, N, N- Dimethylacetamide, N-methyl-2-pyrrolidone, N-
Amides such as methylpyrrolidinone and hexamethylphosphorotriamide can be mentioned. As the base used in <Method 3>, the same base as described in <Method 1> can be used. The reaction is carried out at a temperature of from 0 ° C. to the reflux temperature of the solvent used, preferably from room temperature to 50 ° C. The reaction time depends mainly on the reaction temperature, the starting compound, the reaction reagent or the type of the solvent used, but is usually from 10 minutes to 3 minutes.
Days, preferably 30 minutes to 1 day.

In <Method 1>, <Method 2> and <Method 3>, by appropriately adjusting the equivalent of the acylating agent used to compound (5), 1 to 3 acyl groups are added to compound (5). The introduced compound (6) can be obtained.

After completion of the reaction, the target compound (6) of this reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, an immiscible organic solvent such as water and ethyl acetate are added, and after washing with water, the organic layer containing the target compound is washed. It is obtained by separating and drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. If necessary, the obtained target compound can be obtained by a conventional method, for example, recrystallization, reprecipitation, or, usually,
Methods commonly used for separation and purification of organic compounds, for example,
Adsorption column chromatography using a carrier such as silica gel, alumina, magnesium-silica gel florisil; Sephadex LH-20 (manufactured by Pharmacia), Amberlite XAD-11 (manufactured by Rohm and Haas), diamond A method using a synthetic adsorbent such as distribution column chromatography using a carrier such as Ion HP-20 (manufactured by Mitsubishi Kasei), or a normal-phase / reverse-phase column chromatography method using silica gel or alkylated silica gel (preferably Is a high-performance liquid chromatography.), And can be separated and purified by eluting with an appropriate eluent. (Step C-2) In this step, compound (6) is prepared in an inert solvent.
In this step, the t-butoxycarbonyl group is removed to produce a compound (1c) as an active ingredient of the present invention.

This step can be performed in the same manner as in step A-2.

When Wa is ^a carboxyl-protecting group, the compound which is the active ingredient of the present invention can be obtained by further removing them in the same manner as in Step A-2.

(Method D)

[0077]

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Method D is a method for producing a compound (2a) which is one of the starting compounds of Method A and Method B using a starting compound (7) which can be easily obtained by a method described later. (Step D-1) In this step, compound (7) was added in an inert solvent.
To produce a compound (8).

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether; Ethers such as tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol; and preferred are halogenated hydrocarbons and methanol.

The base to be used is not particularly limited as long as it does not affect other functional groups (for example, methyl ester), and is preferably, for example, sodium methoxide or potassium methoxide. Alkali metal methoxides.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After the completion of the reaction, for example, the target product can be obtained by neutralizing the reaction solution with a hydrochloric acid / dioxane solution and distilling off the solvent under reduced pressure to purify the residue obtained by silica gel chromatography.

(Step D-2) This step is carried out in an inert solvent
In this step, compound (9) is produced by reacting compound (8) with a reagent for introducing an isopropylidene group.

Examples of the solvent used include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; diethyl ether, diisopropyl ether, Ethers such as tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone, and cyclohexanone; ketones (especially acetone) are preferred .

As a reagent to be used, 2,2-dimethoxypropane is preferable, and an acid such as p-toluenesulfonic acid is usually used as a catalyst.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, a water-immiscible solvent such as ethyl acetate and aqueous sodium hydrogencarbonate are added to the reaction solution, and the desired product is extracted with ethyl acetate or the like. Obtainable. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Step D-3) In this step, if desired, 1) substituting the methyl group of the methyl carboxylate moiety with another group, 2) hydrolyzing the methyl carboxylate moiety, or 3) 2) In this step, a carboxylic acid protecting group is introduced after the hydrolysis step.

(Transesterification) In this step, the compound (9) is reacted with an alcohol capable of obtaining a desired ester group in an inert solvent in the presence of a base to give a compound (1).
0).

The solvent used is not particularly limited as long as it does not inhibit the reaction, but is preferably an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether; Aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene;
Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, Isobutanol, t-butanol,
Examples thereof include alcohols such as isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve. Preferably, an alcohol forming a desired ester group is used as a solvent.

The base used is preferably an organic base such as pyridine, triethylamine, diethylamine, 4-N, N-dimethylaminopyridine.

After completion of the reaction, for example, the reaction solution is neutralized with an acid, a water-immiscible solvent such as ethyl acetate is added, the target substance is extracted with ethyl acetate or the like, and after washing, the solvent is distilled off. Thus, an object can be obtained. If necessary, the desired product can be further purified by recrystallization or various types of chromatography.

(Hydrolysis) In this step, compound (9) is hydrolyzed in an inert solvent in the presence of a base to give compound (1).
0).

Examples of the solvent used include aromatic hydrocarbons such as benzene and toluene, ethers such as diethyl ether and tetrahydrofuran, halogenated hydrocarbons such as dichloromethane and chloroform, and acetone and methyl ethyl ketone. Examples thereof include ketones, water, or a mixed solvent of these organic solvents and water.

Examples of the base used include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and alkali metal bicarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After the completion of the reaction, for example, the reaction solution is cooled and made weakly acidic with dilute hydrochloric acid or the like, and then a water-immiscible solvent such as ethyl acetate is added to the reaction solution, and the desired product is extracted with ethyl acetate or the like. The desired product can be obtained by distilling off the solvent. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Diphenylmethylation) This step is a step of reacting compound (9) with diphenyldiazomethane in an inert solvent in the presence of a Lewis acid to produce compound (10).

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aliphatic solvent such as hexane, heptane, ligroin or petroleum ether. Hydrocarbons, aromatic hydrocarbons such as benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, dichloroethane, halogenated hydrocarbons such as chlorobenzene, diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxy Ethers such as ethane, ethylene glycol dimethyl ether,
Methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol,
Alcohols such as methyl cellosolve are mentioned, and more preferably, alcohols (particularly methanol), halogenated hydrocarbons (dichloromethane) and a mixed solvent thereof.

The Lewis acid used is preferably a trifluoroborane-ether complex.

The reaction temperature is usually 0 to 50 ° C.
Preferably, it is room temperature.

The reaction time varies depending on the starting material, Lewis acid and reaction time, but is usually from 10 minutes to 5 hours, preferably from 1 to 3 hours.

After completion of the reaction, the desired product can be obtained, for example, by distilling off the solvent and purifying by recrystallization or chromatography.

(Step D-4) This step is carried out in an inert solvent
This is a step of producing a compound (11) from the compound (10) using a reducing agent.

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; Aromatic hydrocarbons such as benzene, toluene, xylene; Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol , N-propanol, isopropanol
Alcohols such as toluene, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; acetone, methyl ethyl ketone, methyl isobutyl ketone, Ketones such as isophorone and cyclohexanone; nitriles such as acetonitrile and isobutyronitrile; formamide, N, N
Amides such as dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidinone, hexamethylphosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; fatty acids such as acetic acid And mixed solvents of these with water, preferably alcohols (particularly methanol), ethers such as tetrahydrofuran and dioxane, fatty acids such as acetic acid, or mixed solvents of these organic solvents and water. is there.

As the reducing agent to be used, it is preferable to use a catalyst such as palladium carbon, platinum or Raney-nickel in the presence of hydrogen gas. In particular, a Lindlar catalyst (Pd-B
ASO ₄ or Pd-CaCO ₃ and quinoline or first acid
Lead is used in combination).

The reaction temperature is usually from -10 to 50 ° C, preferably from 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the reaction solution is filtered under reduced pressure to remove the catalyst, and the solvent is distilled off under reduced pressure to obtain the desired product. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Step D-5) In this step, compound (1) was prepared in an inert solvent.
1) is a step of producing the compound (2a) of the present invention by removing the isopropylidene group.

The solvent used is preferably a halogenated hydrocarbon such as methylene chloride and chloroform.

The reagent used for the removal is preferably an acid, and the acid is not particularly limited as long as it is used as an acid catalyst in a usual reaction, but hydrochloric acid, hydrobromic acid, sulfuric acid , Perchloric acid, inorganic acids such as phosphoric acid or Bronsted acids or zinc chlorides such as organic acids such as formic acid, oxalic acid, methanesulfonic acid, paratoluenesulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid,
Examples thereof include Lewis acids such as tin tetrachloride, boron trichloride, boron trifluoride, and boron tribromide, and acidic ion exchange resins, and are preferably organic acids (particularly, trifluoroacetic acid).

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used,
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the reaction product is neutralized, and the solvent is distilled off under reduced pressure, and the residue obtained is purified by silica gel chromatography to obtain the desired product. (Method E)

[0111]

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The method E is a method for producing a compound (2b) or (2c) which is one of the starting compounds of the methods A and B using the starting compound (10a) which can be easily obtained by the above-mentioned method. It is.

(Step E-1) This step is carried out in an inert solvent
In this step, a desired acyl group is introduced into compound (10a) to produce compound (12).

This step can be carried out in the same manner as the above-mentioned step C-1. (Step E-2) In this step, compound (1) was prepared in an inert solvent.
2) is removed from the compound (1) by removing the isopropylidene group.
This is the step of manufacturing 3).

This step can be carried out in the same manner as in the above-mentioned step D-5.

(Step E-3) This step is carried out in an inert solvent
In this step, the desired starting compound (2b) is produced from the compound (13) using a reducing agent.

This step can be carried out in the same manner as in the above-mentioned step D-4. (Step E-4) This step is a step of producing compound (14) of the present invention by treating compound (12) with a reagent for removing an isopropylidene group in an inert solvent in the presence of an acid catalyst. It is.

As a solvent to be used, a mixed solvent of acetic acid (also used as an acid catalyst) and water is preferable.

The reaction temperature is usually from 10 to 70 ° C.
Preferably it is 30 to 60 ° C. The reaction time varies depending on the starting material, base, reaction temperature and the like used, but is usually 15 minutes to 24 hours, preferably 10 to 20 hours.

After completion of the reaction, for example, the solvent is distilled off under reduced pressure, a solvent not mixed with water such as ethyl acetate and aqueous sodium hydrogen carbonate are added to the reaction solution, and the target substance is extracted with ethyl acetate or the like. The desired product can be obtained by distillation. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (E-5) In this step, using a reducing agent in an inert solvent,
In this step, the desired starting compound (2c) is produced from the compound (14).

This step can be performed in the same manner as in the above-mentioned step D-4. (Method F)

[0122]

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The method F is a method for producing a compound (2d) or (2e) which is one of the starting compounds of the methods A and B using the starting compound (14) which can be easily obtained by the above-mentioned method. It is.

(Step F-1) This step is carried out in an inert solvent
The compound (14) is reacted with a reagent for protecting a hydroxyl group,
This is a step of producing a compound (15).

The protecting group is not particularly limited.
An rt-butyldimethylsilyl group or a tert-butyldiphenylsilyl group is preferred.

The silylation can be carried out by a usual method. For example, the reaction can be carried out by reacting tert-butyldimethylsilyl halide (particularly chloride) in dimethylformamide in the presence of a base such as triethylamine or 4- (N, N-dimethylamino) pyridine.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 40 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 24 hours, preferably 10 to 20 hours.

After completion of the reaction, for example, a water-immiscible solvent such as ethyl acetate and aqueous sodium hydrogencarbonate are added to the reaction solution, and the target substance is extracted with ethyl acetate or the like. Obtainable. If necessary, the desired product can be further purified by recrystallization or various types of chromatography.

(Step F-2) This step is carried out in an inert solvent
In this step, a desired acyl group is introduced into compound (15) to produce compound (16).

This step can be performed in the same manner as in step C-1. (Step F-3) In this step, compound (1) was prepared in an inert solvent.
Step (6) is a step of producing a compound (17) by reacting a reagent for removing a hydroxyl-protecting group (preferably a tert-butyldimethylsilyl group or a tert-butyldiphenylsilyl group).

The solvent used is preferably an alcohol such as methanol or ethanol, water or a mixed solvent thereof.

The reagent used for the removal is preferably an acid, and the acid is not particularly limited as long as it can be used as an acid catalyst in a usual reaction. Hydrochloric acid, hydrobromic acid, sulfuric acid, Inorganic acids such as perchloric acid and phosphoric acid or Bronsted acids such as acetic acid, formic acid, oxalic acid, organic acids such as methanesulfonic acid, paratoluenesulfonic acid, trifluoroacetic acid and trifluoromethanesulfonic acid, or zinc chloride and tetrachloride Examples thereof include Lewis acids such as tin, boron trichloride, boron trifluoride, and boron tribromide, or acidic ion exchange resins, and are preferably organic acids (particularly acetic acid and trifluoroacetic acid).

If desired, a reagent that generates fluorine ions, such as tetrabutylammonium fluoride, can be used.

The reaction temperature is usually from -10 to 50 ° C, preferably from 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used, but is usually 1 hour.
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the target product can be obtained by neutralizing the reaction solution and distilling off the solvent under reduced pressure to purify the residue obtained by silica gel chromatography.

In this step, the 8-position acyl group (R ⁷ ) is transferred to the 9-position.

(Step F-4) In this step, if necessary, the hydroxyl group at the 8-position of compound (17) is protected by 1) or 2) a desired acyl group is introduced to give compound (18) This is the step of manufacturing. (Introduction of acyl group) This step can be carried out in the same manner as in step C-1.

(Introduction of Protecting Group) As the protecting group, tert-
A butyldimethylsilyl group is preferred, the protecting group being carried out with tert-butyldimethylsilyl triflate and lutidine in methylene chloride.

(Step F-5) This step is carried out in an inert solvent
In this step, the desired starting compound (2d) is produced from the compound (18) using a reducing agent.

This step can be carried out in the same manner as in step D-4.

(Step F-6) This step is carried out in an inert solvent
In this step, the desired starting compound (2e) is produced from the compound (16) using a reducing agent.

This step can be performed in the same manner as in step D-4.

(Method G)

[0144]

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In the method G, the compound (17) or (1
This is a method for producing a compound (2f) or (2g) which is one of the starting compounds of the method A or the method B using 8).

(Step G-1) This step is carried out in an inert solvent
In this step, a desired acyl group is introduced into compound (13) to produce compound (19).

This step can be carried out in the same manner as in step C-1.

(Step G-2) This step is carried out in an inert solvent
In this step, the desired starting compound (2f) is produced from the compound (19) using a reducing agent.

This step can be carried out in the same manner as in step D-4.

(Step G-3) This step is carried out in an inert solvent
In this step, a desired acyl group is introduced into compound (14) to produce compound (20).

This step can be carried out in the same manner as in step C-1.

(Step G-4) This step is carried out in an inert solvent
In this step, a desired starting compound (2 g) is produced from compound (20) using a reducing agent.

This step can be carried out in the same manner as in step D-4.

(Method H)

[0155]

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[0156]

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[0157]

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Method H is described in Carbohydrate Research, 83,163-
169 (1980) or a known compound (21) or WO
This is a method for producing a compound (5) which is a starting compound of the method C using a known compound (26) described in U.S. Pat.

(Step H-1) This step is carried out in an inert solvent
In this step, a compound (22) is produced by reacting the compound (21) with an alkyl halide in the presence of a base.

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; formamide, N, N-dimethyl Formamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N
Amides such as methylpyrrolidinone and hexamethylphosphorotriamide; sulfoxides such as dimethylsulfoxide and sulfolane; and amides (particularly dimethylformamide).

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably, lithium hydride, sodium hydride,
Alkali metal hydrides such as potassium hydride; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, lithium methoxide; sodium methyl mercaptan, ethyl mercaptan Mercaptan alkali metals such as sodium; N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline,
4- (N, N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methylpyridine, quinoline, N,
N-dimethylaniline, N, N-diethylaniline,
1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5.
4.0] Organic bases such as undec-7-ene (DBU) or organic metal bases such as butyllithium, lithium diisopropylamide, lithium bis (trimethylsilyl) amide, and more preferably alkali metal Hydrides, especially sodium hydride.

The alkyl halide used is preferably an alkyl bromide or an alkyl iodide.

The reaction temperature is usually 0 to 50 ° C., preferably room temperature.

The reaction time varies depending on the starting material, base, reaction temperature and the like to be used, but is usually 15 minutes to 24 hours, preferably 2 to 10 hours.

After the completion of the reaction, for example, a water-immiscible solvent such as ethyl acetate and aqueous sodium hydrogen carbonate are added to the reaction solution, and the desired product is extracted with ethyl acetate or the like. Obtainable. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Step H-2) In this step, compound (2) was prepared in an inert solvent.
This is a step of producing compound (23) by reacting 2) with a reducing agent.

Examples of the solvent used include alcohols such as methanol and ethanol, tetrahydrofuran,
Ethers such as dioxane, fatty acids such as acetic acid, or a mixed solvent of these organic solvents and water can be mentioned, and acetic acid is preferable.

Examples of the reducing agent to be used include palladium carbon, platinum and Raney-nickel, preferably palladium carbon.

The reaction temperature is usually from 0 to 50 ° C., preferably room temperature.

The reaction time varies depending on the starting material, base, reaction temperature and the like to be used, but is usually 15 minutes to 24 hours, preferably 2 to 10 hours.

After completion of the reaction, for example, the reduction catalyst is removed by filtration.
The solvent is distilled off, and the obtained residue is purified by recrystallization or various types of chromatography to obtain the desired product. (Step H-3) In this step, compound (2) was prepared in an inert solvent.
3) reacting sodium pyruvate in the presence of N-acetyl-neuraminic acid aldolase and sodium azide to produce compound (24).

The solvent used is preferably water.

The reaction temperature is usually from 0 to 50 ° C., preferably room temperature.

The reaction time varies depending on the starting material, base, reaction temperature and the like to be used, but is usually 5 hours to 5 days, preferably 1 to 3 days.

After completion of the reaction, the desired product can be obtained by, for example, desalting using a cation exchange resin and further purifying by chromatography using an anion exchange resin.

(Step H-4) This step is a step of producing a compound (25) by esterifying the compound (24) in a methanol solvent in the presence of an acid.

The acid to be used is not particularly limited as long as it is used as an acid catalyst in a usual reaction, but is preferably selected from hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid and phosphoric acid. Inorganic acids or Bronsted acids such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, paratoluenesulfonic acid, trifluoroacetic acid, organic acids such as trifluoromethanesulfonic acid or zinc chloride, tin tetrachloride, boron trichloride, boron Examples thereof include Lewis acids such as trifluoride and boron tribromide, or cation exchange resins, and are preferably cation exchange resins.

The reaction temperature is usually from 0 to 50 ° C., preferably room temperature.

The reaction time varies depending on the starting material, base, reaction temperature and the like used, but is usually 1 to 48 hours, preferably 5 to 24 hours.

After completion of the reaction, for example, the cation exchange resin is removed by filtration, the solvent is distilled off, and the obtained residue is purified by recrystallization or various types of chromatography to obtain the desired product. (Step H-5) In this step, compound (2) was prepared in an inert solvent.
This is the step of acetylating 5).

This step can be carried out in the same manner as in step C-1, using acetyl chloride, acetic anhydride and the like. (Step H-6) This step is a step of reacting the compound obtained in Step H-5 with hydrogen chloride in an inert solvent to chlorinate the compound.

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; Are ethers (particularly dioxane).

The reaction temperature is usually from 0 to 50 ° C., preferably room temperature.

The reaction time varies depending on the starting material, base, reaction temperature and the like used, but is usually 5 hours to 2 days, preferably 10 to 24 hours.

After the completion of the reaction, the solvent and hydrogen chloride were distilled off under reduced pressure, and used directly in the next reaction. (Step H-7) In this step, the compound obtained in Step H-6 is reacted with a base in an inert solvent, followed by dehydrochlorination to produce compound (26a).

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; Are aromatic hydrocarbons (particularly benzene).

The base to be used is not particularly limited as long as it is used as an acid catalyst in a usual reaction. Preferably, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide,
Alkali metal alkoxides such as potassium t-butoxide and lithium methoxide; mercaptan alkali metals such as sodium methyl mercaptan and sodium ethyl mercaptan; N-methylmorpholine, triethylamine, tripropylamine, tributylamine;
Diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino)
Pyridine, 2,6-di (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-
Diethylaniline, 1,5-diazabicyclo [4.3.
0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5.4.0] undec-7-ene (DB
Organic bases such as U), and more preferably,
DBU.

The reaction temperature is usually from 0 to 50 ° C., preferably room temperature.

The reaction time varies depending on the starting material, base, reaction temperature and the like to be used, but is usually 5 hours to 2 days, preferably 10 to 24 hours.

After completion of the reaction, for example, a water-immiscible solvent such as methylene chloride and ammonium chloride water are added to the reaction solution, and the desired product is extracted, and the solvent is distilled off to obtain the desired product. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Step H-8) In this step, compound (26a) obtained in step H-7 or known compound (26) is prepared in an inert solvent.
And reacting the compound with an azidating agent to produce the compound (27).

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aromatic hydrocarbon such as benzene, toluene and xylene; Halogenated hydrocarbons such as methylene chloride and chloroform; ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane and nitriles such as acetonitrile can be mentioned.

The reagent to be used is not particularly limited as long as it is usually used for azidation. Preferably, the reagent is a diarylphosphate azide derivative such as diphenylphosphate azide; trimethylsilyl azide or triethylsilyl azide. Examples thereof include trialkylsilyl azides or alkali metal azides such as sodium azide and potassium azide, and preferably sodium azide.

The reaction temperature is usually -10 to 50 ° C, preferably 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used,
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, the reaction solution is neutralized with a hydrochloric acid / dioxane solution, the solvent is distilled off under reduced pressure, and the residue obtained is purified by silica gel chromatography to obtain the desired product. (Step H-9) In this step, compound (2) was prepared in an inert solvent.
This is a step of producing compound (28) by reacting 7) with a t-butoxycarbonylating agent.

The t-butoxycarbonylation is carried out in an inert solvent (for example, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as methylene chloride and chloroform, diethyl ether, tetrahydrofuran and dioxane). Ethers, amides such as dimethylformamide), bases (e.g., 4- (N, N
-Dimethylamino) pyridine) in the presence of
-Butyl dicarbonate or 2- (tert-butoxycarbonyloxyimino) -2-phenylacetonitrile.

After completion of the reaction, the reaction solution was neutralized, the solvent and the like were distilled off under reduced pressure, a water-immiscible solvent such as ethyl acetate and water were added, and the desired product was extracted with ethyl acetate and the like. The desired product can be obtained by distillation. If necessary
Further, the target substance can be purified by recrystallization or various types of chromatography.

(Step H-10) In this step, compound (28) is reacted with a base in an inert solvent to give compound (2).
This is the step of manufacturing 9).

This step can be carried out in the same manner as in step D-1.

(Step H-11) This step is a step of acetylating compound (29) in an inert solvent.

Acetylation is carried out by a conventional method for protecting a hydroxyl group. For example, 1) reacting acetic anhydride in pyridine or 2) in methylene chloride in a base catalyst (eg, triethylamine, 4-N,
(N-dimethylaminopyridine) in the presence of acetyl halide (particularly chloride).

After completion of the reaction, the solvent and the like are distilled off under reduced pressure, a water-immiscible solvent such as ethyl acetate and aqueous sodium hydrogencarbonate are added, and the desired product is extracted with ethyl acetate and the like, and the solvent is distilled off. Thus, an object can be obtained. If necessary, the desired product can be further purified by recrystallization or various types of chromatography. (Step H-12) In this step, the step H-11 is carried out in an inert solvent.
This is a step of producing a compound (30) by treating the compound obtained in the step with a reagent for removing a t-butoxycarbonyl group.

The removal of the t-butoxycarbonyl group is carried out by a usual method.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Preferably, it is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene, xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; formamide, N, N-dimethylformamide;
Amides such as N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidinone, hexamethylphosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; Hydrogens (especially methylene chloride)
It is.

The reagent to be used is not particularly limited as long as it is usually used, but hydrochloric acid is preferred.

The reaction temperature is usually from -10 to 50 ° C, preferably from 10 to 30 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used,
The duration is 5 minutes to 24 hours, preferably 1 to 10 hours.

After completion of the reaction, for example, the solvent and the like are distilled off under reduced pressure, a solvent not mixed with water such as ethyl acetate and aqueous sodium hydrogen carbonate are added to the reaction solution, and the target substance is extracted with ethyl acetate and the like. The desired product can be obtained by distilling off. If necessary, the desired product can be further purified by recrystallization or various types of chromatography.

(Step H-13) This step is a step of introducing a desired acyl group into compound (30) in an inert solvent.

This step can be carried out in the same manner as in step C-1.

(Step H-14) In this step, compound (31) is produced by reacting the compound obtained in step H-13 with a reagent for converting a carbonyl group to a thiocarbonyl group in an inert solvent. It is a process.

Examples of the solvent used include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, chloroform, carbon tetrachloride, Halogenated hydrocarbons such as dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether;
Ethers such as diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether are mentioned, and ethers (particularly, tetrahydrofuran) are preferred.

[0210] The reagent used was Lawson (La).
Wesson's) reagents are preferred.

[0211] The reaction temperature is usually 10 to 100 ° C, preferably 40 to 70 ° C. The reaction time varies depending on the starting material, base, reaction temperature, etc. used,
The duration is 5 minutes to 10 hours, preferably 1 to 5 hours.

After completion of the reaction, for example, a water-immiscible solvent such as ethyl acetate and aqueous sodium hydrogencarbonate are added to the reaction solution, and the target substance is extracted with ethyl acetate or the like. Obtainable. If necessary, the desired product can be further purified by recrystallization or various types of chromatography.

(Step H-15) In this step, compound (31) was converted to compound (3) using a reducing agent in an inert solvent.
This is the step of manufacturing 2).

This step can be carried out in the same manner as in step D-4.

(Step H-16) In this step, compound (32) was prepared in an inert solvent in the presence of a base and mercuric chloride.
Is reacted with N, N'-di-t-butoxycarbonylthiourea to produce compound (33).

This step can be performed in the same manner as in step A-1.

(Step H-17) In this step, compound (33) is reacted with a base in an inert solvent to give compound (3)
This is the step of manufacturing 4).

This step can be carried out in the same manner as in step D-1.

(Step H-18) Transesterification, hydrolysis and protection In this step, if desired, 1) substituting the methyl group of the methyl carboxylate with another group, or 2) hydrolyzing the methyl carboxylate Or 3) a step of introducing a carboxylic acid protecting group after the hydrolysis step 2).

This step can be carried out in the same manner as in step D-3.

Compound (1) which is the active ingredient of the present invention
It can also be produced by a method other than those described above. In particular, the compound (1), which is an active ingredient of the present invention, can be produced by changing the order of the above steps in some cases.

The novel 2-deoxy-2,3-dihydro-N-acylneuraminic acid derivative (1), which is an active ingredient of the present invention, has excellent sialidase inhibitory activity and inhibits influenza virus replication. INDUSTRIAL APPLICABILITY The present invention is useful as a medicine, and particularly useful as a prophylactic and therapeutic agent for influenza.

When the present invention is used as a medicament, examples of the administration form include oral administration or intranasal administration using a solution such as a solution, an aqueous co-solvent solvent, an aerosol, a powder and the like. Among these preparations, liquid preparations such as solutions and aqueous co-solvents include purified water, pharmacologically acceptable organic solvents (eg, ethanol, propylene glycol, PEG400, etc.), and stabilizers (paraoxyl such as methylparaben and propylparaben). Alcohols such as benzoic acid esters, chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid and the like; Sols are propellants such as various CFCs and nitrogen gas Produced by a known method using a surfactant such as lecithin, powders the excipient (e.g., lactose, sucrose, glucose, mannitol, sugar derivatives such as sorbitol; corn starch, potato starch,
starch derivatives such as α-starch, dextrin, carboxymethyl starch; cellulose derivatives such as crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, internally cross-linked sodium carboxymethylcellulose; gum arabic; dextran Organic excipients such as pullulan:
Silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate and magnesium metasilicate aluminate; phosphates such as calcium phosphate; carbonates such as calcium carbonate; sulfates such as calcium sulfate. Excipients may be mentioned. ), Lubricants (eg, metal stearates such as stearic acid, calcium stearate, magnesium stearate; talc; colloidal silica; waxes such as veegum, gay wax; boric acid; adipic acid; Sulfate; glycol;
Fumaric acid; sodium benzoate; DL leucine; fatty acid sodium salt; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; it can. ), Stabilizers (paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; Acetic acid; and sorbic acid), flavoring agents (for example, commonly used sweeteners, sour agents, flavors, and the like), diluents, and the like, in a known manner. Manufactured.

The amount of the main drug used varies depending on symptoms, age, administration method and the like. For example, in the case of liquid preparations, the lower limit of the main drug is 0.1 mg per day (preferably 1 mg).
mg), as an upper limit 1000 mg (preferably 500 m
g), in the case of dry powder,
The lower limit is 0.1 mg (preferably 1 mg) and the upper limit is 1000 mg (preferably 500 mg). In the case of an aerosol, the lower limit is 0.1 mg (preferably 1 mg) per dose as the main drug. , As an upper limit, 1000
mg (preferably 500 mg) one to several times a day,
It is desirable to administer according to the symptoms.

Formulation Example 1 10% of the compound of Example 1
(W / W), 0.04% of benzalkonium chloride (W / W)
W), 0.40% of phenylethyl alcohol (W /
W), an aqueous solution is prepared so that the purified water becomes 89.56% (W / W).

(Formulation Example 2) 10% of the compound of Example 1
(W / W), 0.04% of benzalkonium chloride (W / W)
W), polyethylene glycol 400 is 10.0% (W
/ W), an aqueous co-solvent solution is prepared so that propylene glycol is 30% (W / W) and purified water is 39.96% (W / W).

Formulation Example 3 40% of the compound of Example 1
(W / W), a dry powder is prepared so that lactose is 60% (W / W).

Formulation Example 4 The compound of Example 1 was 10%
(W / W), lecithin 0.5% (W / W), Freon 1
An aerosol is prepared so that 1 is 34.5% and Freon 12 is 55%.

[0229]

In the examples, MeOH represents methanol and E
tOAc indicates ethyl acetate, DMF indicates N, N-dimethylformamide, and THF indicates tetrahydrofuran.

Example 1 5-Acetamide-4- (C-aminooxy-C-imino
Methylamino) -7-O-hexanoyl-2,3,4
5-tetradeoxy-D-glycero-D-galacto-no
2-enopyranosonic acid (Exemplified Compound No. 76-1)

[0231]

Embedded image

(I) 5-acetamido-4-azido-2,
3,4,5-tetradeoxy-D-glycero-D-gala
5-acetamido-7,8,9 was added to methyl methanol of ct-non-2-enopyranosonic acid (20 ml).
-Tri-O-acetyl-4-azido-2,3,4,5-
Tetradeoxy-D-glycero-D-galacto-non-
Methyl 2-enopyranosonate (7 g, 15.3 mmol) was dissolved, and methanol containing sodium methoxide (4.9 M, 0.2 ml, 0.98 mmol) was added dropwise at room temperature with stirring. The reaction solution was stirred at room temperature for 2 hours, and then a hydrochloric acid-containing dioxane solution (4M) was added dropwise to adjust the pH to 6 to 7, and then concentrated to dryness under vacuum. The residue obtained was chromatographed (silica gel, 10: 1 methylene chloride: methanol) to give the title compound as a colorless solid (3.
56 g, 69%).

[0233] Rf = 0.63 (5: 1 = CH 2 Cl 2: MeOH) MS (FAB) m / e 331 (M + + H) [α] D 25 = +28.4 ° (c = 0.21, MeOH) IR ( cm ^-1 ) 2100, 1731, 1657 ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 5.92 (1H, d, J =
2.3 Hz), 4.34 (1H, dd, J = 9.3 Hz, 2.5 Hz), 4.27
(1H, dd, J = 10.7 Hz, 1.2 Hz), 4.13 (1H, dd, J = 1
0.8 Hz, 9.4 Hz), 3.82-3.92 (2H, m), 3.79 (3H, s),
3.66 (1H, dd, J = 11.4 Hz, 5.0Hz), 3.60 (1H, br.d,
J = 9.3 Hz), 2.03 (3H, s).

(Ii) 5-acetamido-4-azido-8,
9-O-isopropylidene-2,3,4,5-tetrade
Oxy-D-glycero-D-galacto-non-2-eno
The compound ( 3.33 g, 10.1 mmol) obtained in Example 1 (i) was dissolved in methyl acetone pyranosone (10 ml), and 2,2-dimethoxypropane (3.7 ml, 30 ml) was stirred at room temperature under stirring. . 2mm
ol) and p-toluenesulfonic acid monohydrate (100 mg,
0.52 mmol) and stirred for 30 minutes. Ethyl acetate (200 ml) and a saturated aqueous solution of sodium hydrogen carbonate (60 ml) were added to the reaction solution, and the mixture was partitioned. The organic layer was separated, and the mixture was washed three times with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and further with saturated saline (50 ml). Washed once, dried over sodium sulfate and evaporated under reduced pressure to give a residue. The residue obtained was chromatographed (silica gel, 2: 1 = ethyl acetate: hexane) to give the title compound as a colorless solid (3.2).
4 g, 87%).

[0235] Rf = 0.38 (20: 1 = CH 2 Cl 2: MeOH) MS (FAB) m / e 371 (M + + H) [α] D 25 = +160.93 ° (c = 0.32, CHCl 3) IR (cm ^-1 ) 2094, 1734, 1656 ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 5.98 (1H, d, J =
2.5 Hz), 5.66 (1H, br.d, J = 6.9 Hz), 4.32-4.41
(1H, m), 4.03-4.28 (6H, m), 3.81 (3H, s), 3.57 (1
H, dd, J = 7.9 Hz, 5.2 Hz), 2.12 (3H, s), 1.66 (1
H, s), 1.39 (3H, s), 1.36 (3H, s).

(Iii) 5-acetamido-4-azido-7-
O-hexanoyl-8,9-O-isopropylidene-
2,3,4,5-tetradeoxy-D-glycero-D-
The compound obtained in Example 1 (ii) (1.35 g, 3.65 mmol) was dissolved in methylene chloride (30 ml) of methyl galacto-non-2-enopyranosonate , and the solution was stirred.
Under ice-cooling, dimethylaminopyridine (490 mg, 4.01
mmol) and hexanoyl chloride (0.61 ml, 4.37 mm)
ol). After stirring the reaction mixture at room temperature for 30 minutes, triethylamine (0.56 ml) was added dropwise under ice cooling, and the mixture was further stirred at room temperature for 2 days. Ethyl acetate (200ml) in the solution
And a saturated aqueous solution of sodium hydrogen carbonate (100 ml) were added and partitioned. The organic layer was separated, washed with saturated brine (50 ml) three times, dried over sodium sulfate and evaporated under reduced pressure to obtain a residue. . The residue obtained was chromatographed (silica gel, 100: 1 = methylene chloride: methanol) to give the title compound as a yellow oil (0.69 g).
, 34%).

[0237] Rf = 0.46 (20: 1 = CH 2 Cl 2: MeOH) MS (FAB) m / e 469 (M + + H) [α] D 25 = +87.7 ° (c = 0.26, CHCl 3) IR (cm ^-1 ) 2099, 1745, 1660 ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 5.95 (1H, d, J =
2.6 Hz), 5.76 (1H, br.d, J = 7.8 Hz), 5.34 (1H, d
d, J = 5.3 Hz, 1.8 Hz), 4.85 (1H, dd, J = 9.0 Hz,
2.7 Hz), 4.73 (1H, dd, J = 10.4 Hz, 1.7 Hz), 4.39
(1H, dd, J = 11.4 Hz, 6.1 Hz), 4.14 (1H, dd, J = 1
2.3 Hz, 6.3 Hz), 3.95 (1H, dd, J = 8.8 Hz, 6.2 H
z), 3.81 (3H, s), 3.40 (1H, dd, J = 18.7 Hz, 8.6 H
z), 2.28-2.52 (2H, m), 2.02 (3H, s), 1.53-1.72 (2
H, m), 1.37 (3H, s), 1.35 (3H, s), 1.25-1.43 (4H,
m), 0.86-0.94 (3H, m).

(Iv) 5-acetamido-4-amino-7-
O-hexanoyl-8,9-O-isopropylidene-
2,3,4,5-tetradeoxy-D-glycero-D-
The compound (650 mg, 1.38 mmol) obtained in Example 1 (iii) was dissolved in methyl methanol of galacto-non-2-enopyranosonic acid (20 ml), and a Lindlar catalyst (400 ml) was added at room temperature with stirring. The inside of the reaction system was degassed and replaced with hydrogen. After stirring at room temperature for 2 hours, the mixture was filtered under reduced pressure, and the filtrate was evaporated under reduced pressure to obtain a residue. The residue obtained was chromatographed (silica gel, 20: 1 = methylene chloride: methanol, then 10: 1 = methylene chloride: methanol) to give the title compound as a yellow amorphous (0.63 g, 100%). ).

[0239] Rf = 0.17 (10: 1 = CH 2 Cl 2: MeOH) MS (FAB) m / e 443 (M + + H) [α] D 25 = +30.6 ° (c = 0.32, CHCl 3) IR (cm ^-1 ) 1743, 1660 ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 5.97 (1H, d, J =
2.3 Hz), 5.51 (1H, br.d, J = 9.0 Hz), 5.43 (1H, d
d, J = 5.0 Hz, 1.9 Hz), 4.40 (1H, dd, J = 17.2 Hz,
6.5 Hz), 4.37 (1H, dd, J = 9.9 Hz, 1.4 Hz), 4.15
(1H, dd, J = 8.9 Hz, 6.3 Hz), 3.95 (1H, dd, J = 8.
7 Hz, 6.8 Hz), 3.80 (3H, s), 3.73-3.80 (1H, m), 3.
60 (1H, dd, J = 19.0 Hz, 9.3 Hz), 2.24-2.49 (2H,
m), 2.02 (3H, s), 1.53-1.70 (2H, m), 1.37 (3H, s),
1.35 (3H, s), 1.25-1.43 (4H, m), 0.86-0.94 (3H,
m).

(V) 5-acetamido-4-amino-7-O
-Hexanoyl-8,9-O-isopropylidene-2,
3,4,5-tetradeoxy-D-glycero-D-gala
Example 1 was prepared by mixing a mixture of methanol (4 ml) and water (4 ml) of ct-non-2-enopyranosonic acid.
The compound obtained in (iv) (470 mg, 1.06 mmol) was dissolved and lithium hydroxide monohydrate (47 m
g, 1.12 mmol) and stirred for 30 minutes. Then, slowly add Dowex-50W x 8 (H ⁺ ) resin,
The pH was adjusted to 7.5. Immediately thereafter, the resulting suspension was quickly filtered under reduced pressure. The residue obtained by evaporating the filtrate under reduced pressure was chromatographed (silica gel, 2: 5: 1).
= 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (375 mg, 82%). Rf
= 0.26 (2: 5: 1 = 2-Propanol: EtOAc: MeOH) MS (FAB) m / e 429 (M ⁺ + H) [α] _D ²⁵ = +8.3 ° (c = 0.48, CH ₃ OH) IR (cm ^-1 ) 1750, 1666 ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 5.60 (1H, d, J = 2.
1 Hz), 5.41 (1H, dd, J = 5.4 Hz, 1.9 Hz), 4.58 (1H,
t, J = 6.0 Hz), 4.15-4.28 (3H, m), 3.92 (1H, dd, J
= 10.8 Hz, 6.1 Hz), 3.79-3.87 (1H, m), 2.30-2.40
(2H, m), 1.96 (3H, s), 1.53-1.70 (2H, m), 1.35 (3
H, s), 1.32 (3H, s), 1.25-1.43 (4H, m), 0.87-0.96
(3H, m).

(Vi) 5-acetamido-4-amino-7-
O-hexanoyl-2,3,4,5-tetradeoxy-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in Example 1 (v) (270 mg, 0.63 mm
ol) was dissolved in a mixture of acetic acid (12 ml) and water (3 ml) at room temperature and stirred at 60 ° C. for 2 hours 30 minutes. Then, the residue was distilled off under reduced pressure, and the obtained residue was further azeotropically distilled with benzene.
Concentrated to dryness in vacuo. The residue obtained was chromatographed (silica gel, 2: 5: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (174 mg, 71%).

[0242] Rf = 0.32 (5: 1: 1 = 2-Propanol: EtOAc: MeOH) MS (FAB) m / e 389 (M + + H) [α] D 25 = + 1.1 ° (c = 0.14, CH ₃ OH) IR (cm ^-1 ) 1745, 1662 ¹ H-NMR (D ₂ O 270 MHz) d 5.66 (1H, d, J = 2.2 Hz),
5.13 (1H, dd, J = 9.3Hz, 1.7 Hz), 4.47 (1H, dd, J
= 10.5 Hz, 1.3 Hz), 4.17 (1H, t, J = 10.0Hz), 4.00
-4.10 (2H, m), 3.59 (1H, dd, J = 12.0 Hz, 3.1 Hz),
3.39 (1H, dd, J = 12.0 Hz, 6.1 Hz), 2.32-2.39 (2
H, m), 1.91 (3H, s), 1.45-1.63 (2H, m), 1.20-1.28
(4H, m), 0.78-0.86 (3H, m).

(Vii) 5-acetamide-4-cyanamide-
7-O-hexanoyl-2,3,4,5-tetradeoxy
S-D-glycero-D-galacto-non-2-enopyra
The compound obtained in Example 1 (vi) (155 mg, 0.40 mmol) was dissolved in methanol nosonate (4 ml), and sodium acetate (65 mg, 0.80 mmol) and cyanogen bromide (53 mg) were stirred at room temperature at room temperature. , 0.50 mmol). The reaction solution is 4
Stir for 0 min at room temperature, then evaporate under reduced pressure and chromatograph the residue obtained (silica gel, 2: 5: 1 = 2
-Propanol: ethyl acetate: water) to give the title compound as a colorless solid (144 mg, 85%).

[0244] Rf = 0.21 (2: 5: 1 = 2-Propanol: EtOAc: MeOH) MS (FAB) m / e 436 (M + + Na), 452 (M + + K) 1 H-NMR (CD 3 OD 270MHz) δ (ppm): 5.73 (1H, d, J = 1.
0 Hz), 5.07 (1H, dd, J = 7.8 Hz, 1.2 Hz), 4.49 (1
H, d, J = 10.6 Hz), 4.47 (1H, dd, J = 10.5Hz, 1.3
Hz), 4.05-4.18 (2H, m), 3.85 (1H, dd, J = 9.8 Hz,
1.8 Hz), 3.63-3.73 (1H, m), 3.48-3.58 (1H, m), 2.
28-2.48 (2H, m), 1.95 (3H, s), 1.54-1.68 (2H, m),
1.28-1.40 (4H, m), 0.87-0.96 (3H, m).

(Viii) 5-Acetamide-4- (C-amido
Nooxy-C-iminomethylamino) -7-O-hexa
Noyl-2,3,4,5-tetradeoxy-D-glyce
The compound (88 mg, 0.21 mmol) obtained in Example 1 (vii) was dissolved in methanol (4 ml) of 2-D-galacto-non-2-enopyranosonic acid , and hydroxylamine hydrochloride (15 mg) was stirred at room temperature at room temperature. , 0.21 mmol) was added. The reaction solution was stirred for 2 hours 30 minutes at room temperature, then
The residue was evaporated under reduced pressure to give a residue, which was chromatographed (silica gel, 2: 5: 12 = 2-propanol: ethyl acetate:
Water) to give the title compound as a colorless solid. (43
mg, 45%) Rf = 0.50 (5: 1: 1 = 2-propanol: EtOAc: MeOH) MS (FAB) m / e 447 (M + + H) [α] D 25 = +28.0 ° (c = 0.035 , CH ₃ OH) IR (cm ^-1 ) 1727, 1661, 1631 ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 5.57 (1H, d, J = 1.
9 Hz), 5.13 (1H, dd, J = 8.7 Hz, 1.9 Hz), 4.47 (1H,
br.d, J = 10.2 Hz), 4.29 (1H, br.d, J = 9.3 Hz),
4.21 (1H, t, J = 9.9 Hz), 4.00-4.09 (1H, m), 3.58
(1H, dd, J = 8.7 Hz, 3.4 Hz), 3.43 (1H, dd, J = 1
(1.5 Hz, 5.7 Hz), 2.30-2.40 (2H, m), 1.91 (3H, s),
1.52-1.68 (2H, m), 1.28-1.40 (4H, m), 0.88-0.96 (3
H, m) (Example 2) 5-Acetamide-4- (C-aminooxy-C-imino
Methylamino) -2,3,4,5-tetradeoxy-D
-Glycero-D-galacto-non-2-enopyranosone
Acid (Exemplified Compound No. 34-1)

[0246]

Embedded image

(I) 5-Acetamide-4- (C-amino)
(Xy-C-iminomethylamino) -2,3,4,5-te
Toradeoxy-D-glycero-D-galacto-non-2
-The compound (20 mg, 0.05 mmol) obtained in Example 1 (viii) was dissolved in methanol of enopyranosonic acid (20 ml), and methanol containing sodium methoxide (4.9 M, 2.1 m) was stirred at room temperature at room temperature.
l, 0.01 mmol) were added dropwise. The solution was stirred at room temperature for 2 hours, then the pH was adjusted to 6-7 by dropwise addition of hydrochloric acid-containing dioxane solution (4M) and then concentrated to dryness under vacuum. The residue was chromatographed (silica gel, 5:
1: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid. (7.3 mg, 50
%) Rf = 0.30 (4: 1: 1 = 2-Propanol: EtOAc: MeOH) MS (FAB) m / e 325 (M + + H) 1 H-NMR (D 2 O 270MHz) δ (ppm): 5.58 (1H, d, J =
2.0 Hz), 4.42 (1H, dd, J = 10.0 Hz, 2.0 Hz), 4.30
(1H, d, J = 10.0 Hz), 4.20 (1H, dd, J = 10.0 Hz, 1
0.0 Hz), 3.90 (1H, m), 3.85 (1H, dd, J = 12.0 Hz,
2.2 Hz), 3.55-3.65 (2H, m), 1.99 (3H, s).

Example 3 5-Acetamide-4- (C-aminooxy-C-imino
Methylamino) -9-O-hexanoyl-2,3,4
5-tetradeoxy-D-glycero-D-galacto-no
2-enopyranosonic acid (Exemplary Compound No. 34-3)
6)

[0249]

Embedded image

(I) 5-acetamido-4-amino-9-O
-Hexanoyl-2,3,4,5-tetradeoxy-D
-Glycero-D-galacto-non-2-enopyranosone
Acid Compound obtained in Example 1 (vi) (80 mg, 0.21 mmol)
l) with trifluoroacetic acid (3 ml) and methylene chloride (6 m
The mixture was dissolved in l) at room temperature and stirred at room temperature for 6 hours. Subsequently, the residue was distilled off under reduced pressure to obtain a residue, which was further azeotroped with benzene, and concentrated to dryness under vacuum. The residue obtained is chromatographed (silica gel, 2: 5: 1 = 2-propanol:
Ethyl acetate: water) gave the title compound as a colorless solid (55 mg, 68%).

[0251] Rf = 0.39 (5: 1: 1 = 2-Propanol: EtOAc: MeOH) MS (FAB) m / e 389 (M + + H) [α] D 25 = +10.0 ° (c = 0.07, CH ₃ OH) IR (cm ^-1 ) 1724, 1664 ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 5.56 (1H, d, J = 2.
1 Hz), 4.38 (1H, dd, J = 11.1 Hz, 1.9 Hz), 4.30 (1
H, s), 4.28 (1H, d, J = 1.9 Hz), 4.07-4.25 (2H, m),
3.93-4.02 (1H, m), 3.58 (1H, d, J = 9.3 Hz), 2.37
(2H, t, J = 7.4 Hz), 2.04 (3H, s), 1.57-1.71 (2H,
m), 1.27-1.40 (4H, m), 0.88-0.96 (3H, m).

(Ii) 5-acetamide-4-cyanamide-
9-O-hexanoyl-2,3,4,5-tetradeoxy
S-D-glycero-D-galacto-non-2-enopyra
The compound obtained in Example 3 (i) (46 mg, 0.12 mmol) was dissolved in methanol nosonate (10 ml), and sodium acetate (29 mg, 0.35 mmol) and cyanogen bromide (17 mg) were stirred at room temperature under stirring. , 0.16 mmol). The reaction solution is 4
The mixture was stirred for 0 minutes at room temperature and then distilled off under reduced pressure to obtain a residue. The obtained residue was chromatographed (silica gel, 2: 2).
5: 12 = propanol: ethyl acetate: water) to give the title compound as a colorless solid (29 mg, 60%).

[0253] Rf = 0.43 (2: 5: 1 = 2-propanol: EtOAc: MeOH) MS (FAB) m / e 436 (M + + Na), 458 (M + + 2Na - H) [α] D 25 = +8.27 ° (c = 0.075, CH ₃ OH) ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 5.66 (1H, d, J =
2.0 Hz), 3.95-4.36 (6H, m), 3.67 (1H, d, J = 7.4 H
z), 2.36 (2H, t, J = 7.5 Hz), 2.05 (3H, s), 1.55-
1.71 (2H, m), 1.27-1.40 (4H, m), 0.88-0.96 (3H, m)
.

(Iii) 5-Acetamide-4- (C-amino
Oxy-C-iminomethylamino) -9-O-hexano
Yl-2,3,4,5-tetradeoxy-D-glycero
The compound (24 mg, 0.06 mmol) obtained in Example 3 (ii) was dissolved in methanol (4 ml) of -D-galacto-non-2-enopyranosonic acid , and hydroxylamine hydrochloride (4. (5 mg, 0.06 mmol) were added. The reaction was stirred at room temperature for 4 hours and then evaporated under reduced pressure to give a residue, which was chromatographed (silica gel, 2: 5: 1 = 2-propanol: ethyl acetate: water). This afforded the title compound as a colorless solid (18 mg, 70%).

Rf = 0.58 (5: 1: 1 = 2-propanol: EtOAc: MeO
H) MS (FAB) m / e 447 (M ⁺ + H) [α] _D ²⁵ = +39.2 ° (c = 0.025, CH ₃ OH) IR (cm ^-1 ) 1723, 1656, 1630 ¹ H-NMR ( D ₂ O 270MHz) δ (ppm): 5.57 (d, J = 2.0 Hz,
1H), 4.30-4.46 (m, 3H), 4.08-4.25 (m, 3H), 3.68
(d, J = 9.4 Hz, 1H), 2.37 (t, J = 7.3 Hz, 2H), 1.9
8 (s, 3H), 1.50-1.64 (m, 2H), 1.18-1.32 (m, 4H),
0.77-0.86 (m, 3H) (Example 4) 5-acetamido-4- (C-aminooxy-C-imino
Methylamino) -7-O-tetradecanoyl-2,3
4,5-tetradeoxy-D-glycero-D-galacto
-Non-2-enopyranosonic acid (Exemplary Compound No. 106
-1)

[0256]

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(I) 5-acetamido-4-azido-7-O
-Tetradecanoyl-8,9-O-isopropylidene-
2,3,4,5-tetradeoxy-D-glycero-D-
The compound (1.50 g, 4.05 mmol) obtained in Example 1 (ii) was dissolved in methyl methylene chloride (30 ml) of galacto-non-2-enopyranosonic acid , and the solution was stirred.
In an ice bath, dimethylaminopyridine (545 mg, 4.45
mmol) and tetradecanoyl chloride (1.32 ml, 4.8)
6 mmol) was added. The reaction was stirred at room temperature for 40 minutes, then triethylamine (0.62 ml, 4.45) in an ice bath.
mmol) was added dropwise and stirred at room temperature for 20 hours. Ethyl acetate (200 ml) and saturated aqueous sodium hydrogen carbonate solution (100 ml) were added to the reaction solution, and the mixture was partitioned. The organic layer was separated, washed with saturated saline (50 ml) three times, dried over anhydrous sodium sulfate, and the solvent was removed. The residue obtained was evaporated under reduced pressure and the residue obtained was chromatographed (silica gel, 100: 1 = methylene chloride:
Methanol) to give the title compound as a yellow oil (1.57 g, 67%).

[0258] Rf = 0.49 (20: 1 = CH 2 Cl 2: MeOH) MS (FAB) m / e 603 (M + + Na) [α] D 25 = -56.4 ° (c = 0.11, CHCl 3) IR (cm ^-1 ) 2100, 1745, 1661 ¹ H-NMR (CDCl ₃ 270 MHz) δ (ppm): 6.14 (1H, d, J = 5.
8 Hz), 5.77 (1H, br.d, J = 9.8 Hz), 5.42 (1H, dd,
J = 5.2 Hz, 2.1 Hz), 4.37-4.53 (2H, m), 4.10-4.27
(3H, m), 3.94 (1H, dd, J = 8.7 Hz, 6.7 Hz), 3.83 (3
H, s), 2.21-2.47 (2H, m), 1.99 (3H, s), 1.52-1.68
(2H, m), 1.37 (3H, s), 1.35 (3H, s), 1.20-1.48 (20
H, m), 0.85-0.92 (3H, m).

(Ii) 5-acetamido-4-amino-7-
O-tetradecanoyl-8,9-O-isopropylidene
-2,3,4,5-tetradeoxy-D-glycero-D
-The compound (1.50 g, 2.65 mmol) obtained in Example 4 (i) was dissolved in methyl methanol (20 ml) of -galacto-non-2-enopyranosonic acid , and Lindlar catalyst (600 mg) was stirred at room temperature at room temperature. Was added to replace the inside of the reaction system with hydrogen. After stirring at room temperature for 2 hours, the mixture was filtered under reduced pressure using Celite, the filtrate was evaporated under reduced pressure, and the obtained residue was chromatographed (silica gel, 20: 1 = methylene chloride: methanol, then 10: 1). = Methylene chloride: methanol) to give the title compound as a yellow amorphous (710 mg, 50%).

[0260] Rf = 0.29 (10: 1 = CH 2 Cl 2: MeOH) MS (FAB) m / e 555 (M + + H) [α] D 25 = +25.2 ° (c = 0.25 CHCl 3) IR ( cm ^-1 ) 1753, 1738, 1660 ¹ H-NMR (CDCl ₃ 270 MHz) δ (ppm): 5.98 (1H, d, J = 2.
01Hz), 5.61 (1H, br.s), 5.43 (1H, dd, J = 5.1Hz,
1.9 Hz), 4.35-4.45 (2H, m), 4.15 (1H, dd, J = 8.9 H
z, 6.3 Hz), 3.95 (1H, dd, J = 8.9 Hz, 6.8 Hz), 3.8
3 (1H, br.s), 3.80 (3H, s), 3.64 (1H, br.d, J =
8.4 Hz), 2.25-2.50 (2H, m), 2.01 (3H, s), 1.77 (1
H, br.s), 1.53-1.69 (2H, m), 1.37 (3H, s), 1.35
(3H, s), 1.22-1.35 (20H, m), 0.85-0.92 (3H, m).

(Iii) 5-acetamido-4-amino-7-
O-tetradecanoyl-8,9-O-isopropylidene
-2,3,4,5-tetradeoxy-D-glycero-D
-Galacto-non-2-enopyranosonic acid Example 4 was added to a mixture of methanol (4 ml) and water (4 ml).
The compound (710 mg, 1.28 mmol) obtained in (ii) was dissolved, and lithium hydroxide monohydrate (59 m
g, 1.41 mmol) and stirred for 30 minutes. Then, slowly add Dowex-50W x 8 (H ⁺ ) resin,
The pH was adjusted to 7.5. Immediately thereafter, the resulting suspension was quickly filtered under reduced pressure. The residue obtained by evaporating the filtrate under reduced pressure was chromatographed (silica gel, 2: 5: 1 = 2-
Propanol: ethyl acetate: water) to give the title compound as a colorless solid. (490mg, 71%) Rf = 0.29 (2: 5: 1 = 2-propanol: EtOAc: MeOH) MS (FAB) m / e 541 (M + + H) [α] D 25 = +10.8 ° (c = 0.12, CH ₃ OH) IR (cm ^-1 ) 1750, 1666 ¹ H-NMR (CDCl ₃ 270 MHz) δ (ppm): 5.61 (1H, d, J = 1.
9Hz), 5.41 (1H, dd, J = 6.0 Hz, 1.4 Hz), 4.59 (1H,
dd, J = 12.0 Hz, 6.2Hz), 4.13-4.28 (3H, m), 3.93
(1H, dd, J = 9.0 Hz, 6.4 Hz), 3.79-3.86 (1H, m),
2.28-2.42 (2H, m), 1.96 (3H, s), 1.52-1.70 (2H, m),
1.35 (3H, s), 1.33 (3H, s), 1.26-1.43 (20H, m),
0.87-0.95 (3H, m).

(Iv) 5-acetamido-4-amino-7-
O-tetradecanoyl-2,3,4,5-tetradeoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid The compound obtained in Example 4 (iii) (480 mg, 0.89 )
mmol) was dissolved in a mixture of acetic acid (10 ml) and water (10 ml) at room temperature and stirred for 5 hours. Subsequently, the residue was distilled off under reduced pressure, and the obtained residue was further azeotroped with benzene, and concentrated to dryness under vacuum. The obtained residue is chromatographed (silica gel, 2: 5: 1 = 2-propanol: ethyl acetate: water).
To give the title compound as a colorless solid (110 mg,
25%). Rf = 0.37 (5: 1: 1 = 2-propanol: EtOAc: MeOH) MS (FAB) m / e 501 (M ⁺ + H) [α] _D ²⁵ = +7.50 ° (c = 0.07, CH ₃ OH) IR (cm ^-1 ) 1740, 1661 ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 5.59 (1H, d, J =
2.2Hz), 5.14 (1H, dd, J = 9.4 Hz, 1.8 Hz), 4.42 (1
H, dd, J = 10.7 Hz, 1.7 Hz), 4.23 (1H, t, J = 10.1H
z), 4.01-4.09 (1H, m), 3.83 (1H, dd, J = 9.4 Hz,
2.1 Hz), 3.56 (1H, dd, J = 11.8 Hz, 3.2 Hz), 3.40
(1H, dd, J = 11.7 Hz, 6.3 Hz), 2.28-2.38 (2H, m),
1.95 (3H, s), 1.52-1.68 (2H, m), 1.26-1.38 (20H,
m), 0.87-0.95 (3H, m).

(V) 5-acetamide-4-cyanamide-7
-O-tetradecanoyl-2,3,4,5-tetradeo
Xy-D-glycero-D-galacto-non-2-enopi
The compound obtained in Example 4 (iv) (108 mg, 0.22 mmol) was dissolved in methanol lanosonic acid (4 ml), and sodium acetate (46 mg, 0.56 mmol) and cyanogen bromide (31 mg) were stirred at room temperature at room temperature. , 0.29 mmol). Reaction solution is 15
The mixture was stirred for 0 min at room temperature and then distilled off under reduced pressure to obtain a residue. The residue obtained by azeotropic distillation with benzene was chromatographed (silica gel, 2: 5: 1 = 2-propanol: ethyl acetate: water). To give the title compound as a colorless solid (66 mg, 58%).

Rf = 0.30 (2: 5: 1 = 2-propanol: EtOAc: Me
OH) MS (FAB) m / e 526 (M ⁺ + H) [α] _D ²⁵ = -36.3 ° (c = 0.07, CH ₃ OH) IR (cm ^-1 ) 2223, 1746, 1662 ¹ H-NMR ( CD ₃ OD 270MHz) δ (ppm): 5.71 (1H, d, J =
2.1Hz), 5.08 (1H, dd, J = 8.2 Hz, 1.8 Hz), 4.46 (1
H, dd, J = 10.6 Hz, 1.7 Hz), 4.04-4.20 (2H, m), 3.8
5 (1H, dd, J = 9.5 Hz, 2.2 Hz), 3.66 (1H, dd, J =
11.5 Hz, 3.5 Hz), 3.45-3.54 (1H, m), 2.25-2.50 (2
H, m), 1.96 (3H, s), 1.53-1.68 (2H, m), 1.26-1.40
(20H, m), 0.87-0.96 (3H, m).

(Vi) 5-Acetamide-4- (C-amino
Oxy-C-iminomethylamino) -7-O-tetrade
Canoyl-2,3,4,5-tetradeoxy-D-gly
The compound (51 mg, 0.1 mmol) obtained in Example 4 (v) was dissolved in methanol (4 ml) of cello-D-galacto-non-2-enopyranosonic acid , and hydroxylamine hydrochloride (7 mg) was stirred at room temperature at room temperature. .6 mg, 0.1 mmol) were added. The reaction solution was stirred at room temperature for 3 hours, then evaporated under reduced pressure, and the resulting residue was chromatographed (silica gel,
2: 5: 1 = 2-propanol: ethyl acetate: water to give the title compound as a colorless solid (34 mg, 63).
%).

Rf = 0.37 (5: 1: 1 = 2-propanol: EtOAc: Me
OH) MS (FAB) m / e 559 (M ⁺ + H) [α] _D ²⁵ = +22.5 ° (C = 0.065, CH ₃ OH) IR (cm ^-1 ) 1743, 1726, 1664, 1633 ¹ H- NMR (CD ₃ OD 270 MHz) δ (ppm): 5.55 (1H, d, J =
1.9Hz), 5.12 (1H, dd, J = 9.2 Hz, 2.0 Hz), 4.44 (1
H, dd, J = 10.2 Hz, 1.5 Hz), 4.17-4.33 (2H, m), 3.9
8-4.08 (1H, m), 3.56 (1H, dd, J = 11.8 Hz, 3.2 H
z), 3.40 (1H, dd, J = 11.7 Hz, 6.1 Hz), 2.28-2.42
(2H, m), 1.91 (3H, s), 1.53-1.70 (2H, m), 1.26-1.3
9 (20H, m), 0.87-0.94 (3H, m).

Example 5 5-Acetamide-4- (C-aminooxy-C-imino
Methylamino) -9-O-tetradecanoyl-2,3
4,5-tetradeoxy-D-glycero-D-galacto
-Non-2-enopyranosonic acid (Exemplified Compound No. 34-
41)

[0268]

Embedded image

(I) 5-acetamido-4-amino-9-O
-Tetradecanoyl-2,3,4,5-tetradeoxy
-D-glycero-D-galacto-non-2-enopyrano
Sonic acid The compound obtained in Example 4 (iii) (55 mg, 1.01 mm
ol) with trifluoroacetic acid (2 ml) and methylene chloride (4
ml) The mixture was dissolved at room temperature and stirred at room temperature for 3 days. Subsequently, the residue was distilled off under reduced pressure to obtain a residue, and the residue obtained by azeotropic distillation with benzene was concentrated to dryness under vacuum. The obtained residue was subjected to chromatography (silica gel, 2: 5: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (51 mg, 100%).

Rf = 0.49 (5: 1: 1 = 2-propanol: EtOAc: Me
OH) MS (FAB) m / e 501 (M ⁺ + H) [α] _D ²⁵ = +3.56 ° (c = 0.09, CH ₃ OH) IR (cm ^-1 ) 1734, 1628 ¹ H-NMR (CD ₃ OD 270MHz) δ (ppm): 5.68 (1H, d, J =
1.9Hz), 4.01-4.38 (3H, m), 3.84-4.00 (4H, m), 3.71
(1H, d, J = 7.7 Hz), 2.30-2.42 (2H, m), 2.06 (3H,
s), 1.53-1.71 (2H, m), 1.26-1.40 (20H, m), 0.87-
0.93 (3H, m).

(Ii) 5-Acetamide-4-cyanamide-
9-O-tetradecanoyl-2,3,4,5-tetrade
Oxy-D-glycero-D-galacto-non-2-eno
The compound (90 mg, 0.18 mmol) obtained in Example 5 (i) was dissolved in methanol (10 ml) of pyranosonic acid , and sodium acetate (44 mg, 0.54 mmol) and cyanogen bromide (19 mg) were stirred at room temperature under stirring. , 0.18 mmol). The reaction was stirred at room temperature for 10 hours, then evaporated under reduced pressure and the resulting residue was chromatographed (silica gel, 2: 5: 1 = 2-
Propanol: ethyl acetate: water) gave the title compound as a colorless solid (75 mg, 79%).

Rf = 0.52 (2: 5: 1 = 2-propanol: EtOAc: Me
OH) MS (FAB) m / e 526 (M ⁺ + H) [α] _D ²⁵ = -56.7 ° (c = 0.060, CH ₃ OH) ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 5.70 (1H, d, J =
1.9 Hz), 4.05-4.32 (3H, m), 3.78-4.02 (4H, m), 2.3
2-2.38 (2H, m), 2.06 (3H, s), 1.55-1.68 (2H, m),
1.26-1.40 (20H, m), 0.87-0.93 (3H, m).

(Iii) 5-acetamido-4- (C-amino
Oxy-C-iminomethylamino) -9-O-tetrade
Canoyl-2,3,4,5-tetradeoxy-D-gly
The compound (55 mg, 0.11 mmol) obtained in Example 5 (ii) was dissolved in methanol (4 ml) of cello-D-galacto-non-2-enopyranosonic acid , and hydroxylamine hydrochloride (27 mg) was stirred at room temperature at room temperature. , 0.39 mmol). The reaction was stirred at room temperature for 2 hours, then evaporated under reduced pressure and the resulting residue was chromatographed (silica gel, 2: 5: 1 = 2-propanol: ethyl acetate: water).
To give the title compound as a colorless solid (11 mg, 1
9%).

Rf = 0.28 (2: 5: 1 = 2-propanol: EtOAc: Me
OH) MS (FAB) m / e 559 (M ⁺ + H) [α] _D ²⁵ = +53.3 ° (c = 0.015, CH ₃ OH) IR (cm ^-1 ) 1679 ¹ H-NMR (CD ₃ OD 270 MHz ) δ (ppm): 5.53 (1H, d, J =
(1.9 Hz), 4.30-4.43 (2H, m), 4.03-4.28 (3H, m), 3.5
5-3.65 (2H, m), 2.32-2.40 (2H, m), 2.00 (3H, s), 1.
55-1.68 (2H, m), 1.26-1.37 (20H, m), 0.85-0.93 (3
H, m).

Example 6 5-Acetamide-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-fluoro-D-glycero-D-
Galacto-non-2-enopyranosonic acid trifluoro
Acetate (Exemplary Compound No. 1-1)

[0276]

Embedded image

(I) 5-acetamido-4-azido-8,9
-Di-O-acetyl-2,3,4,5,7-pentadeo
Xy-7-fluoro-D-glycero-D-galacto-no
It is prepared according to the methods described in emissions -2 Enopiranoson methyl WO95 / 32955 5- acetamido -4,8,9- tri -O- acetyl -
2,6-anhydro-3,5,7-trideoxy-7-
Methyl fluoro-D-glycero-D-galacto-non-2-enopyranosonate (300 mg, 0.70 mmol) was
Dissolve in anhydrous methylene chloride (10 ml) and add methanol (25 m
g, 0.78 mmol). After replacing the reaction system with nitrogen,
Boron trifluoride ether complex (BF ₃ OEt ₂ ) (1.0 g, 7.0 mmo
l) was added and the mixture was stirred at room temperature for 24 hours. The reaction solution was washed with water (50
ml), ice (10 g), solid sodium bicarbonate (10 g)
) And ethyl acetate (50 ml) and stirred vigorously for 10 minutes. The organic layer was washed with a saturated saline solution (10 ml), dried over sodium sulfate (Na ₂ SO ₄ ), and the solvent was distilled off under reduced pressure. The obtained residue (210 mg) was dissolved in N, N-dimethylformamide (DMF) (4 ml), and the mixture was dissolved in a cation exchange resin (Dowex-50 × 8 (H ⁺ ) (400 mg) and sodium azide (NaN ₃ )). (100 mg, 1.53 mmol) and 8
Stirred at 0 ° C. for 4 hours. After the reaction, dowex 50
x8 (H ⁺ ) was filtered off and the solvent was distilled off under reduced pressure. Ethyl acetate (30 ml) and saturated aqueous sodium hydrogen carbonate solution (20 ml) were added to the obtained residue to dissolve the residue, and the organic layer was washed with saturated saline and dried over sodium sulfate (Na ₂ SO ₄ ). The solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless syrup (170 mg, 59%).

[0278] Rf = 0.31 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = +69.4 ° (c = 0.18, CHCl 3); MS (FAB) m / e 417 (M + + H ); ¹ H-NMR (CDCl ₃ 270 MHz) δ (ppm) 2.07 (9H, s), 3.58
(1H, ddd, J = 9.0,9.0, 9.0), 3.80 (3H, s), 4.22 (1
H, ddd, J = 1.8, 5.2, 13.0 Hz), 4.65-5.00 (4H, m),
5.45 (1H, m), 5.98 (1H, d, J = 2.8Hz), 6.00 (1H,
d, J = 8.5 Hz).

(Ii) 5-Acetamide-4- (N, N'-
Bis-t-butyloxycarbonylguanidino) -8,
9-di-O-acetyl-2,3,4,5,7-pentade
Oxy-7-fluoro-D-glycero-D-galacto-
Methyl non-2-enopyranosonate The compound obtained in Example 6 (i) (36 mg, 0.08 mmol)
l) was dissolved in methanol (3 ml), a Lindlar catalyst (10 mg) was added, the inside of the reaction system was replaced with hydrogen, and the mixture was stirred for 2 hours. The catalyst was filtered off, and the solvent was distilled off under reduced pressure. The residue was dissolved in DMF (2 ml) and N, N'-di-tert-butoxycarbonylthiourea (26 mg, 0.093 mmol) was added.
l), triethylamine (19 mg, 0.186 mg) and mercuric chloride ((HgCl ₂ ) (25 mg, 0.093 mg) were added, and the mixture was stirred at room temperature for 1 hour, and the solid was filtered off. 5 ml) and a saturated aqueous solution of sodium hydrogencarbonate (3 ml), and the organic layer was washed with saturated saline solution.
_After drying over ₂ SO ₄ , the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (2: 1 = ethyl acetate: hexane) to give the title compound as a colorless amorphous (32 mg, 59%).

[0280] Rf = 0.35. (2: 1 = EtOAc: hexane) [α] _D ²⁵ = +5.6 DEG _{(c = 0.16, CHCl 3)} ; MS (FAB) m / e 633 (M + + H); 1 H-NMR (CDCl ₃ 270 MHz) δ (ppm); 1.49 (9H, s), 1.5
2 (9H, s), 1.98 (3H, s), 2.05 (3H, s), 2.07 (3H,
s), 3.80 (3H, s) 4.00-4.30 (3H, m), 4.75 (1H, dd,
J = 9.2, 50 Hz), 4.78 (1H, d, J = 18 Hz), 5.23 (1
H, dd, J = 9.0, 9.0 Hz), 5.43 (1H, m), 5.88 (1H,
d, J = 2.8Hz), 6.80 (1H, d, J = 8.2Hz), 8.60 (1H,
d, J = 8.5 Hz).

(Iii) 5-acetamido-4-guanidino
-2,3,4,5,7-pentadeoxy-7-fluoro
-D-glycero-D-galacto-non-2-enopyrano
Sonoic acid trifluoroacetate Compound obtained in Example 6 (ii) (32 mg, 0.05 mm
ol) was dissolved in methanol (2 ml), 0.1N sodium methoxide methanol solution (0.5 ml) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was neutralized with a hydrochloric acid-containing dioxane solution (4M), and the solvent was distilled off. The residue was methylene chloride-
It was dissolved in trifluoroacetic acid (3: 1) (6 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, the obtained residue was dissolved in distilled water (1 ml), and a 1N aqueous sodium hydroxide solution (70 ml) was added.
ml) and stirred at room temperature for 1 hour. Dowex 50
x8 (H ⁺ ) was added to neutralize the reaction solution, and water was distilled off.
The obtained residue is subjected to silica gel chromatography (5:
Purification with 1: 1 = 2-propanol: ethyl acetate: water) afforded the title compound as a colorless solid (16 mg, 71).
%).

Rf = 0.30 (4: 1: 1 = 2-propanol: acetic acid: water); [α] _D ²⁵ = + 28.0 ° (c = 0.10, H ₂ O); MS (FAB) m / e 335 ( M ⁺ + H); ¹ H ^- NMR (D ₂ O, 270 MHz) δ (ppm); 2.00 (3H, s), 3.
65 (1H, ddd, J = 2.4, 5.5, 12.0 Hz), 3.85 (1H, dd
d, J = 2.5, 2.5, 12 Hz), 4.15 (1H, m), 4.23 (1H,
d, J = 9.0 Hz), 4.30-4.60 (3H, m), 5.63 (1H, s).

Example 7 5-Acetamide-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-fluoro-D-glycero-D-
Galacto-non-2-enopyranosonic acid myristilt
Lifluoroacetate (Exemplary Compound No. 1-5)

[0284]

Embedded image

(I) 5-acetamido-4-azido-8,9
-O-isopropylidene-2,3,4,5,7-penta
Deoxy-7-fluoro-D-glycero-D-galacto
-Methyl non-2-enopyranosonate The compound obtained in Example 6 (i) (300 mg, 0.72 mmol)
l) was dissolved in methanol (5 ml), 1 M sodium methoxide / methanol solution (0.2 ml) was added, and the mixture was stirred at room temperature for 1 hour. After neutralizing the reaction solution with a 4M hydrochloric acid / dioxane solution, the solvent was distilled off. The resulting residue was dissolved in acetone (5 ml) and 2,2-dimethoxypropane (400
mg, 3.85 mmol) and p-toluenesulfonic acid (20 mg,
0.11 mmol) and stirred at room temperature for 3 hours. The solid was filtered off, and the filtrate was distilled off under reduced pressure. Silica gel chromatography of the residue (50: 1 = methylene chloride: methanol)
To give the title compound as a colorless amorphous (140 mg, 52%).

Rf = 0.33 (20: 1 = CH ₂ Cl ₂ : MeOH); [α] _D ²⁵ = + 111 ゜ (c =
0.13, CHCl ₃ ); MS (FAB) m / e 373 (M ⁺ + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 1.37 (3H, s),
1.42 (3H, s), 2.05 (3H, s), 3.50 (1H, ddd, J = 7.
5 7.5, 9.5 Hz), 3.80 (3H, s), 4.13 (1H, ddd, J =
1.2, 6.0, 9.0), 4.20 (1H, ddd, J = 1.2, 6.0, 9.
0), 4.45 (1H., M), 4.70 (1H, ddd, J = 1.5, 5.7,
47.0 Hz), 4.90 (1H, dd, J = 2.8, 9.5 Hz), 4.92
(1H, ddd, J = 1.0, 11.0, 28.0 Hz), 5.90 (1H, d, J =
7.3 Hz), 5.96 (1H, d, J = 2.8 Hz).

(Ii) 5-acetamido-4-azido-8,9
-O-isopropylidene-2,3,4,5,7-penta
Deoxy-7-fluoro-D-glycero-D-galacto
-Myristyl non-2-enopyranosonate The compound obtained in Example 7 (i) (113 mg, 0.31 m
mol) in methanol: water (6: 1) (4 ml)
An aqueous potassium hydroxide solution (0.33 ml) was added, and the mixture was added at room temperature for 2 hours.
Stirred for hours. The solvent was distilled off, followed by drying under reduced pressure at room temperature for 2 hours to obtain a pale yellow solid. This solid was dissolved in acetonitrile (8 ml) and 18-crown-6 (80 mg, 0.1 mg) was added.
3mml), myristyl bromide (415mg, 1.5mmo)
l) was added and the mixture was stirred at 80 ° C for 2 hours. The reaction solution was diluted with ethyl acetate (15 ml) and a saturated aqueous solution of sodium hydrogen carbonate (10 ml).
ml), and the organic layer was washed with saturated saline, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless syrup (110 mg, 64%).

[0288] Rf = 0.47 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = +52.9 ° (c = 0.09, CHCl 3); MS (FAB) m / e 555 (M + + H ); ¹ H ^- NMR (CDCl ₃ , 270 MHz) δ (ppm); 0.80-0.95 (3H,
s), 1.20-1.50 (24H, m), 1.37 (3H, s), 1.42 (3H,
s), 1.60-1.80 (2H, m), 2.05 (3H, s), 4.10-4.30 (2
H, m), 4.45 (1H., M), 4.72 (1H, ddd, J = 1.5, 5.
3, 38.0 Hz), 4.90 (1H, dd, J = 2.4, 9.3 Hz), 4.92
(1H, ddd, J = 1.0, 10.0, 28.0 Hz), 5.97 (1H, d, J =
6.5 Hz), 5.95 (1H, d, J = 2.4 Hz).

(Iii) 5-Acetamide-4- (N, N'-
Bis-t-butyloxycarbonylguanidino) -8,
9-O-isopropylidene-2,3,4,5,7-pen
Tadeoxy-7-fluoro-D-glycero-D-galact
Myristyl tonone-2-enopyranosonate The compound obtained in Example 7 (ii) (110 mg, 0.20 mmol)
Was dissolved in methanol (5 ml) and Lindlar's catalyst (30
mg), the inside of the reaction system was replaced with hydrogen, and the mixture was stirred for 2 hours. After completion of the reaction, the catalyst was filtered off and the solvent was distilled off under reduced pressure. The residue was dissolved in dimethylformamide (4 ml),
, N-di-t-butoxycarbonylthiourea (47 m
g, 0.17 mmol), triethylamine (35 mg, 0.342 m
g) and mercuric chloride (HgCl ₂ ) (47 mg, 0.17 mg) were added, and the mixture was stirred at room temperature for 1 hour. The solid was filtered off and the filtrate was washed with ethyl acetate (15 ml) and saturated aqueous sodium hydrogen carbonate (10 mL).
ml), and the organic layer was washed with saturated saline, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (2: 1 = ethyl acetate: hexane) to give the title compound as a colorless syrup (98 mg, 63%).

[0290] Rf = 0.30 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 2.2 ° (c = 0.14, CHCl 3); MS (FAB) m / e 771 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 0.80-0.95 (3H,
s), 1.20-1.40 (24H, m), 1.36 (3H, s), 1.41 (3H,
s), 1.49 (9H, s), 1.50 (9H, s), 1.60-1.80 (2H, m),
2.05 (3H, s), 4.10-4.70 (6H, m), 5.20 (1H, ddd,
J = 2.4, 7.5, 7.5 Hz), 5.83 (1H, d, J = 2.4 Hz), 5.
65 (1H, d, J = 7.0 Hz), 8.60 (1H, d, J = 8.5 Hz).

(Iv) 5-Acetamide-4-guanidino-
2,3,4,5,7-pentadeoxy-7-fluoro-
D-glycero-D-galacto-non-2-enopyranoso
Myristyl trifluoroacetate Compound obtained in Example 7 (iii) (80 mg, 0.11 mmol)
To methylene chloride-trifluoroacetic acid (3: 1) (6 ml)
And stirred at room temperature for 4 hours. The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 8: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (40 mg, 56%).

Rf = 0.35 (5: 1: 1 = tert-butyl alcohol: acetic acid: water); [α] _D ²⁵ = + 22.4 ° (c = 0.13, CH ₃ OH); MS (FAB) m / e 531 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm); 0.70-0.85 (3H, s),
1.10-1.30 (24H, m), 1.50-1.80 (2H, m), 2.00 (3H,
s), 3.60-3.80 (2H, m), 4.10-4.30 (3H, m) 4.40-4.60
(2H, m), 5.88 (1H, s).

Example 8 5-thioacetamido-4-guanidino-2,3,4
5-tetradeoxy-D-glycero-D-galacto-no
2-enopyranosonic acid trifluoroacetate (Exemplary Compound No. 31-1)

[0294]

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(I) 5-Acetamide-4- (N, N'-bi
Tert-butyloxycarbonylguanidino) -7,8,
9-tri-O-acetyl-2,3,4,5-tetradeo
Xy-D-glycero-D-galacto-non-2-enopi
Methyl lanosonate 5-acetamido-4-amino-7,8,9-tri-O-
Methyl acetyl-3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enopyranosonate (2.0 g, 4.63 mmol) was added to dimethylformamide (40 m).
was dissolved in l), N, N'- bis -t- butoxycarbonyl thiourea (1.54 g, 5.58 mmol), triethylamine (1.1 g, 11.2 mmol) and mercuric chloride (HgCl ₂₎ (1.54
g, 5.58 mmol) and stirred at room temperature for 2 hours. The insoluble material was filtered off, and the filtrate was poured into a two-layer solution of ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogen carbonate (25 ml).
The organic layer was washed with brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained is chromatographed on silica gel (1: 1 = ethyl acetate: hexane).
The title compound was obtained as a colorless amorphous (3.0 g, 96%).

Rf = 0.20 (1: 1 = ethyl acetate: hexane) ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 1.49 (18H, s),
1.88 (3H, s), 2.07 (3H, s), 2.09 (3H, s), 2.13 (3
H, s), 3.80 (3H, s) 4.15 (1H, dd, J = 8.0,13.0 H
z), 4.20-4.30 (2H, m), 4.67 (1H, dd, J = 3.0, 13.0
Hz), 5.15 (1H, ddd, J = 2.5, 8.5, 8.5 Hz), 5.30 (1
H, m), 5.43 (1H, dd, J = 2.5, 5.3 Hz), 5.90 (1H,
d, J = 2.5 Hz), 6.20 (1H, d, J = 8.2 Hz), 8.50 (1H,
d, J = 8.5 Hz).

(Ii) 5-thioacetamido-4- (N,
N'-bis-t-butyloxycarbonylguanidino)
-7,8,9-Tri-O-acetyl-2,3,4,5-
Tetradeoxy-D-glycero-D-galacto-non-
Methyl 2-enopyranosonate The compound obtained in Example 8 (i) (1.95 g, 2.89 mmol)
Was dissolved in tetrahydrofuran (40 ml), Lawesson's reagent (2.15 g, 5.32 mmol) was added, and the mixture was stirred at 60 ° C for 2 hours. The reaction solution was poured into a two-layer solution of ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogen carbonate (30 ml).
The organic layer was washed with brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue is chromatographed on silica gel (2: 1 = ethyl acetate: hexane).
The title compound was obtained as a colorless amorphous (1.0 g, 50%).

. [0298] Rf = 0.40 (1: 1 = EtOAc: ^{_{hexane) [α] D 25 = +19.0}} ° (c = 0.11, CHCl 3); MS (FAB) m / e 689 (M + + H); 1 H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 1.46 (9H, s), 1.49
(9H, s), 1.95 (3H, s), 1.97 (3H, s), 1.99 (3H, s),
2.42 (3H, s), 3.80 (3H, s) 4.15 (1H, dd, J = 8.0,
13.0 Hz), 4.45 (1H, dd, J = 3.0, 8.5 Hz), 4.70 (1
H, dd, J = 3.0, 13.0 Hz), 5.20-5.35 (3H, m), 5.40
(1H, dd, J = 2.5, 4.5 Hz), 5.92 (1H, d, J = 2.5H
z), 7.95 (1H, d, J = 8.2 Hz), 8.55 (1H, d, J = 8.5
Hz).

(Iii) 5-thioacetamido-4-guani
Dino-2,3,4,5-tetradeoxy-D-glycero
-D-Galacto-non-2-enopyranosonic acid trif
Fluoroacetate Compound obtained in Example 8 (ii) (800 mg, 1.16 mmol)
Was dissolved in methanol (10 ml), a 0.1 N sodium methoxide / methanol solution (1.5 ml) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was neutralized with a 4M hydrochloric acid / dioxane solution, and the solvent was distilled off under reduced pressure. The obtained residue was mixed with methylene chloride and trifluoroacetic acid (3: 1, 20 m
l) and stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and the obtained residue was dissolved in distilled water (10 ml).
-Add an aqueous sodium hydroxide solution (2.0 ml) and add
Stirred for hours. Dowex 50 ^× 8 (H ⁺ ) was added to neutralize the reaction solution, and water was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (5: 1: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (215 mg, 40%).

Rf = 0.30 (4: 1: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 41.0 ° (c = 0.11, H ₂ O); MS (FAB) m / e 349 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm); 2.51 (3H, s), 3.55
(1H, d, J = 10 Hz), 3.62 (1H, dd, J = 7.0, 14.0 H
z), 3.85 (1H, dd, J = 3.5, 14.0 Hz), 3.92 (1H, m),
4.40-4.60 (2H, m), 4.50 (1H, m), 5.63 (1H, d, J =
2.5 Hz).

Example 9 5-Thioacetamido-4-guanidino-2,3,4
5-tetradeoxy-D-glycero-D-galacto-no
Hexyl-2-enopyranosonate trifluoroacetic acid
Salt (Exemplary Compound No. 31-3)

[0302]

Embedded image

(I) 5-thioacetamido-4- (N,
N'-bis-t-butyloxycarbonylguanidino)-
8,9-O-isopropylidene-2,3,4,5-tetra
Radeoxy-D-glycero-D-galacto-non-2-
Methyl enopyranosonate The compound obtained in Example 8 (ii) (700 mg, 1.01 mmol) was dissolved in methanol (20 ml), 1 M sodium methoxide / methanol solution (0.2 ml) was added, and the mixture was stirred at room temperature for 1 hour. did. After completion of the reaction, the reaction solution was neutralized with a 4 M hydrochloric acid / dioxane solution, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in acetone (30 ml), 2,2-dimethoxypropane (1.0 g, 9.71 mmol) and p-toluenesulfonic acid (40 mg, 0.22 mmol) were added, and the mixture was stirred at room temperature for 3 hours. Next, solid sodium hydrogen carbonate (100 mg) was added, and the mixture was stirred for 30 minutes. The solid was filtered off and the filtrate was distilled off. The obtained residue is subjected to silica gel chromatography (5
Purification with 0: 1 methylene chloride: methanol) afforded the title compound as a colorless amorphous (450 mg, 74).
%).

[0304] Rf = 0.33 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = +14.4 ° (c = 0.18, CHCl 3); MS (FAB) m / e 603 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 1.37 (3H, s), 1.41
(3H, s), 1.48 (9H, s), 1.51 (9H, s), 2.55 (3H,
s), 3.50 (1H, dd, J = 4.8, 8.5 Hz), 3.80 (3H, s),
4.05 (1H, dd, J = 5.0, 9.0), 4.13 (1H, dd, J =
7.3, 9.2), 4.20 (1H, d, J = 10.0 Hz), 4.40 (1H.,
m), 4.55 (1H, ddd, J = 7.4, 10.0, 10.0 Hz), 5.3
0 (1H, ddd, J = 2.4, 8.0, 10.0 Hz), 5.84 (1H, d,
J = 2.8 Hz), 8.68 (1H, J = 8.0 Hz), 9.04 (1H, J =
7.2 Hz).

(Ii) 5-thioacetamido-4- (N, N'-
Bis-t-butyloxycarbonylguanidino) -8,9
-O-isopropylidene-2,3,4,5-tetradeo
Xy-D-glycero-D-galacto-non-2-enopi
Hexyl lanosonate The compound obtained in Example 9 (i) (190 mg, 0.31 mmol)
l) was dissolved in methanol: water (6: 1) (12 ml).
M potassium hydroxide aqueous solution (0.32 ml) was added, and the mixture was stirred at room temperature for 3 hours. The solvent was distilled off, followed by drying under reduced pressure at room temperature for 2 hours to obtain a pale yellow solid. This solid was dissolved in acetonitrile (8 ml) and 18-crown-6 (76 mg, 0.1 mg) was added.
29 ml) and hexyl bromide (236 mg, 1.43)
mmol) and stirred at 80 ° C. for 2 hours. The reaction solution was treated with ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogen carbonate (2 mL).
0 ml), and the organic layer was washed with saturated saline, dried over sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (3: 1 = ethyl acetate: hexane) to give the title compound as a colorless amorphous (73 mg, 35%).

[0306] Rf = 0.57 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} +19.2 ° (c: 0.12, CHCl 3); MS (FAB) m / e 673 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 0.85-0.95 (3H,
s), 1.20-1.50 (8H, m), 1.36 (3H, s), 1.41 (3H, s),
1.48 (9H, s), 1.51 (9H, s), 1.60-1.80 (2H, m), 2.56
(3H, s), 3.52 (1H, dd, J = 4.8, 8.5 Hz), 4.00-4.
30 (3H, m), 4.40 (1H., M), 4.55 (1H, ddd, J =
7.4, 10.0, 10.0 Hz), 5.30 (1H, ddd, J = 2.2, 8.0,
10.0 Hz), 5.82 (1H, d, J = 2.2 Hz), 8.68 (1H, J =
8.0 Hz), 9.02 (1H, J = 7.2 Hz).

(Iii) 5-thioacetamido-4-guani
Dino-2,3,4,5-tetradeoxy-D-glycero
-D-galacto-non-2-hexanopyranosonic acid hexyl
Trifluoroacetic acid salt The compound obtained in Example 9 (ii) (100 mg, 0.15 mmol)
l) was converted to methylene chloride-trifluoroacetic acid (3: 1) (12
ml) and stirred at room temperature for 4 hours. Evaporate the solvent,
The residue was chromatographed on silica gel (15: 1: 1 =
Purification with tert-butyl alcohol: ethyl acetate: water) afforded the title compound as a colorless solid (65 mg, 79%).

Rf = 0.75 (5: 1: 1 = tert-butyl alcohol: acetic acid: water); [α] _D ²⁵ = -1.9 ° (c: 0.11, CH ₃ OH); MS (FAB) m / e 433 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm); 0.70-0.85 (3H, s),
1.10-1.40 (8H, m), 1.60-1.70 (2H, m), 2.50 (3H,
s), 3.51 (1H, d, J = 8.5 Hz), 3.80 (1H, d, J =
10.0 Hz), 4.20 (2H, m), 4.40-4.70 (2H, m), 5.10 (1
H., m), 5.98 (1H, brs).

Example 10 5-Thioacetamido-4-guanidino-2,3,4
5-tetradeoxy-D-glycero-D-galacto-no
Myristyl-2-enopyranosonate trifluorovinegar
Acid salt (Exemplary compound No. 31-5)

[0310]

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(I) 5-thioacetamido-4- (N,
N'-bis-t-butyloxycarbonylguanidino)-
8,9-O-isopropylidene-2,3,4,5-tetra
Radeoxy-D-glycero-D-galacto-non-2-
Myristyl enopyranosonate The compound obtained in Example 9 (i) (234 mg, 0.39 m
mol) in a mixture of methanol and water (6: 1) (12 ml)
And a 1M aqueous solution of potassium hydroxide (0.43 ml) was added, followed by stirring at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and dried under reduced pressure at room temperature for 2 hours to obtain a pale yellow solid. This solid was dissolved in acetonitrile (8 ml) and 18-crown-
6 (103 mg, 0.39 mmol) and myristyl bromide (593 mg, 1.94 mmol) were added and stirred at 80 ° C. for 2 hours. After completion of the reaction, the reaction solution was poured into a two-layer solution of ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogen carbonate (20 ml), and the organic layer was washed with saturated saline, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. I left. The residue obtained is chromatographed on silica gel (3: 1 = ethyl acetate:
Hexane) to give the title compound as a colorless amorphous (100 mg, 33%).

[0312] Rf = 0.45 (2: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} +18.2 ° (c = 0.11, CHCl 3); MS (FAB) m / e 785 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 0.85-0.95 (3H,
s), 1.20-1.50 (24H, m), 1.36 (3H, s), 1.40 (3H,
s), 1.48 (9H, s), 1.51 (9H, s), 1.60-1.80 (2H, m),
2.54 (3H, s), 3.51 (1H, dd, J = 4.8, 8.5 Hz), 4.
00-4.30 (3H, m), 4.40 (1H., M), 4.55 (1H, ddd, J
= 7.4, 10.0, 10.0 Hz), 5.30 (1H, ddd, J = 2.2, 8.0,
10.0 Hz), 5.82 (1H, d, J = 2.2 Hz), 8.66 (1H, J
= 8.0 Hz), 9.00 (1H, J = 7.2 Hz).

(Ii) 5-thioacetamido-4-guanidinium
No-2,3,4,5-tetradeoxy-D-glycero-
Myristyl D-galacto-non-2-enopyranosonate
Trifluoroacetic acid salt Compound obtained in Example 10 (i) (90 mg, 0.11 mmol)
l) as a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (12 ml) and stirred at room temperature for 4 hours. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel chromatography (5: 1: 1 = tertiary butyl alcohol: ethyl acetate: water) to obtain the title compound as a colorless solid (40 mg, 47 mg). %).

Rf = 0.80 (5: 1: 1 = tert-butyl alcohol: acetic acid: water); [α] _D ²⁵ = -1.4 ° (c = 0.15, CH ₃ OH); MS (FAB) m / e 545 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm); 0.70-0.85 (3H, s),
1.10-1.40 (24H, m), 1.60-1.70 (2H, m), 2.50 (3H,
s), 3.60-3.90 (2H, m),, 4.15 (2H, m), 4.40-4.70
(2H, m), 5.10 (1H., M), 5.90 (1H, brs).

(Example 11) 5-Thioacetamido-4-guanidino-9-O-hexa
Sanoyl-2,3,4,5-tetradeoxy-D-gly
Cello-D-galacto-non-2-enopyranosonic acid
Lifluoroacetate (Exemplified Compound No. 31-36)

[0316]

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(I) 5-thioacetamido-4- (N, N'-
Bis-t-butyloxycarbonylguanidino) -7-O
-Hexanoyl-8,9-O-isopropylidene-2,
3,4,5-tetradeoxy-D-glycero-D-gala
Methyl ct-non-2-enopyranosonate The compound obtained in Example 9 (i) (500 mg, 0.83 mmol
Was dissolved in methylene chloride (15 ml), dimethylaminopyridine (110 mg, 0.91 mmol) and hexanoyl chloride (122 mg, 0.91 mmol) were added, and the mixture was stirred at room temperature for 30 minutes. Further, triethylamine (92 m
g, 0.91 mmol) and stirred for 15 hours. The reaction solution was poured into a two-layer solution of ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (15 ml), and the organic layer was washed with brine, dried over sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (50: 1 =
Purification with methylene chloride: methanol) afforded the title compound as a colorless amorphous (432 mg, 74%).

[0318] Rf = 0.30 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = -18.0 ° (c = 0.10, CHCl 3); MS (FAB) m / e 701 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 0.85-0.95 (3H,
s), 1.20-1.70 (6H, m), 1.35 (3H, s), 1.38 (3H, s),
1.47 (9H, s), 1.48 (9H, s), 2.20-2.50 (2H, m), 2.4
2 (3H, s), 3.80 (3H, s), 3.92 (1H, dd, J = 6.6,
8.5 Hz), 4.10 (1H, dd, J = 6.2, 8.5 Hz), 4.35-4.4
5 (2H, m), 5.15-5.35 (2H, m), 5.90 (1H, d, J = 2.0
Hz), 7.55 (1H, J = 10.0 Hz), 8.55 (1H, J = 9.5 Hz)
.

(Ii) 5-thioacetamido-4- (N,
N'-bis-t-butyloxycarbonylguanidino)
-7-O-hexanoyl-8,9-O-isopropylide
-2,3,4,5-tetradeoxy-D-glycero-
D-Galacto-non-2-enopyranosonic acid The compound obtained in Example 11 (i) (89 mg, 0.13 mm
ol) was dissolved in a mixture of methanol and water (6: 1) (3 ml) and 1M lithium hydroxide monohydrate (5.5 mg, 0.13
mmol) and stirred at room temperature for 3 hours. The reaction solution was neutralized with a 4M hydrochloric acid / dioxane solution, and the solvent was distilled off. The residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (48 mg, 64%).

Rf = 0.67 (2: 5: 1 = 2-propanol: EtOAc: water); [α] _D ²⁵ = −25.0 ° (c = 0.10, CHCl ₃ ); MS (FAB) m / e 687 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm); 0.85-0.95 (3H,
s), 1.20-1.70 (6H, m), 1.32 (3H, s), 1.35 (3H,
s), 1.45 (9H, s), 1.51 (9H, s), 2.20-2.50 (2H, m),
2.35 (3H, s), 3.40 (1H, m), 4.20 (1H, dd, J = 6.
2, 8.5 Hz), 4.40 (1H, dd, J = 1.5, 10.0 Hz), 4.55
(1H, m), 5.00 (1H, dd, J = 10.0, 10.0Hz), 5.10 (1
H, dd, J = 2.1, 10.0 Hz), 5.30 (1H, dd, J = 2.0,
5.5 Hz), 5.73 (1H, d, J = 2.1 Hz).

(Iii) 5-thioacetamido-4-guani
Dino-9-O-hexanoyl-2,3,4,5-tetra
Deoxy-D-glycero-D-galacto-non-2-e
Nopyranosonic acid trifluoroacetate Compound obtained in Example 11 (ii) (100 mg, 0.15 mm
ol) was dissolved in a mixture of methylene chloride, trifluoroacetic acid and thiophenol (12: 6: 1) (12 ml) and stirred at room temperature for 8 hours. The solvent was distilled off, and the obtained residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (54 mg, 53%).

Rf = 0.55 (5: 1: 1 = tert-butyl alcohol: ethyl acetate: water); [α] _D ²⁵ = + 2.3 ° (c = 0.10, CH ₃ OH); MS (FAB) m / e 447 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm); 0.70-0.85 (3H,
s), 1.20-1.70 (6H, m), 2.30-2.50 (2H, m), 2.52 (3
H, s), 3.51 (1H, d, J = 8.5 Hz), 4.15 (1H, m), 4.2
3 (1H, dd, J = 5.5, 12.0 Hz), 4.35 (1H, dd, J =
2.5, 12.0 Hz), 4.40-4.60 (2H, m), 5.10 (1H., M), 5.
63 (1H, d, J = 2.4 Hz).

Example 12 5-Thioacetamido-4-guanidino-9-O-tet
Ladecanoyl-2,3,4,5-tetradeoxy-D-
Glycero-D-galacto-non-2-enopyranosonic acid
Trifluoroacetic acid salt (Exemplary Compound No. 31-41)

[0324]

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(I) 5-thioacetamido-4- (N,
N'-bis-t-butyloxycarbonylguanidino)-
7-O-tetradecanoyl-8,9-O-isopropyl
Den-2,3,4,5-tetradeoxy-D-glycero
Methyl -D-galacto-non-2-enopyranosonate The compound obtained in Example 9 (i) (440 mg, 0.73 mmol)
Was dissolved in methylene chloride (15 ml), dimethylaminopyridine (132 mg, 1.08 mmol) and tetradecanoyl chloride (247 mg, 1.0 mmol) were added, and the mixture was stirred at room temperature for 30 minutes. Further, triethylamine (10
9 mg, 1.08 mmol) and stirred for 15 hours. The reaction solution was poured into a two-layer solution of ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (15 ml), and the organic layer was washed with brine, dried over sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (50: 1).
= Methylene chloride: methanol) to give the title compound as a colorless amorphous (350 mg, 59%).

[0326] Rf = 0.35 (1: 1 = ethyl acetate: ^{_{hexane); [α] D 25 =}} -17.6 ° (c = 0.15, CHCl 3); MS (FAB) m / e 813 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm); 0.85-0.95 (3H,
s), 1.20-1.70 (22H, m), 1.35 (3H, s), 1.38 (3H,
s), 1.47 (9H, s), 1.49 (9H, s), 2.20-2.50 (2H, m),
2.42 (3H, s), 3.80 (3H, s), 3.92 (1H, dd, J =
6.6, 8.5 Hz), 4.10 (1H, dd, J = 6.2, 8.5 Hz), 4.3
5-4.45 (2H, m), 5.15-5.35 (2H, m), 5.90 (1H, d, J =
2.0 Hz), 7.55 (1H, J = 10.0 Hz), 8.55 (1H, J = 9.5
Hz).

(Ii) 5-thioacetamido-4- (N,
N'-bis-t-butyloxycarbonylguanidino)-
7-O-tetradecanoyl-8,9-O-isopropyl
Den-2,3,4,5-tetradeoxy-D-glycero
-D-Galacto-non-2-enopyranosonic acid The compound obtained in Example 12 (i) (320 mg, 0.39
mmol) in a mixture of methanol and water (6: 1, 7 ml) and 1 M lithium hydroxide monohydrate (18 mg, 0.4).
1 mmol) and stirred at room temperature for 3 hours. 4N-hydrochloric acid /
The reaction solution was neutralized with a dioxane solution, and the solvent was distilled off. The residue was purified by silica gel chromatography (5: 1 = methylene chloride: methanol) to give the title compound as a colorless solid (240 mg, 77%).

Rf = 0.30 (10: 1 = CH ₂ Cl ₂ : MeOH); [α] _D ²⁵ = −25.0 ° (c = 0.12, CHCl ₃ ); MS (FAB) m / e 799 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm); 0.85-0.95 (3H,
s), 1.20-1.70 (22H, m), 1.32 (3H, s), 1.35 (3H,
s), 1.45 (9H, s), 1.50 (9H, s), 2.20-2.50 (2H, m),
2.35 (3H, s), 3.95 (1H, dd, J = 6.2, 8.5 Hz), 4.
20 (1H, dd, J = 6.2, 8.5 Hz), 4.40 (1H, dd, J =
1.5, 10.0 Hz), 4.55 (1H, m), 5.00 (1H, dd, J = 10.
0, 10.0 Hz), 5.10 (1H, dd, J = 2.1, 10.0 Hz), 5.30
(1H, dd, J = 2.0, 5.5 Hz), 5.73 (1H, d, J = 2.1 H
z).

(Iii) 5-thioacetamido-4-guani
Dino-9-O-tetradecanoyl-2,3,4,5-te
Toradeoxy-D-glycero-D-galacto-non-2
-Enopyranosonic acid trifluoroacetate Compound obtained in Example 12 (ii) (220 mg, 0.27 m
mol) was dissolved in a mixture of methylene chloride, trifluoroacetic acid and thiophenol (2: 6: 1) (12 ml) and stirred at room temperature for 8 hours. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the target compound as a colorless solid (120 mg, 56%). ).

Rf = 0.60 (5: 1: 1 = tert-butyl alcohol: acetic acid: water); [α] _D ²⁵ = + 2.2 ° (c = 0.10, CH ₃ OH); MS (FAB) m / e 559 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm); 0.70-0.85 (3H, s),
1.20-1.70 (22H, m), 2.30-2.50 (2H, m), 2.54 (3H,
s), 3.61 (1H, d, J = 8.5 Hz), 4.15 (1H, m), 4.20
(1H, dd, J = 5.5, 12.0 Hz), 4.30 (1H, dd, J = 2.
5, 12.0 Hz), 4.40-4.60 (2H, m), 5.10 (1H., M), 5.
60 (1H, brs).

Example 13 5-Acetamide-4-guanidino-9-O-hexanoy
-2,3,4,5,7-pentadeoxy-7-fluoro
B-D-Glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 1-3
6) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
(Xycarbonylguanidino) -2,3,4,5,7-pe
Ntadeoxy-7-fluoro-D-glycero-D-gala
Diphenylmethyl ct-non-2-enopyranosonate The compound obtained in Example 6 (ii) (100 mg, 0.24 mmol)
Was dissolved in methanol (3 ml), 0.1N sodium methoxide / methanol solution (0.5 ml) was added, and the mixture was stirred at room temperature for 1 hour. Next, the reaction solution was neutralized with a 4 M hydrochloric acid / dioxane solution, and the solvent was distilled off. The obtained residue was dissolved in distilled water (1 ml), and a 1N aqueous sodium hydroxide solution (28 ml) was added.
0 ml) and stirred at room temperature for 1 hour. Next, the reaction solution was neutralized with a 4 M hydrochloric acid / dioxane solution, and water was distilled off.
The obtained residue was mixed with 3 ml of a mixture of methanol and water (6:
1) dissolved in diphenyldiazomethane (100 mg, 0.52 m
mol) and boron trifluoride etherate (BF ₃ OEt ₂ ) (8 mg,
0.06 mmol) and stirred at room temperature for 2 hours. After completion of the reaction, acetic acid was added to the reaction solution, the solvent was distilled off, and the residue was purified by silica gel chromatography (20: 1 = methylene chloride: methanol) to obtain the title compound as a colorless amorphous (82 mg). , 50%).

[0332] Rf = 0.45 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -12.2 ° (c = 0.1, CHCl 3); MS (FAB) m / e 701 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm) 1.50 (9H, s), 1.5
1 (9H, s), 1.95 (3H, s), 3.25 (2H, m), 3.90 (2H,
m), 4.20-4.70 (3H, m), 5.25 (1H, m), 5.95 (1H, d, J
= 2.5 Hz), 6.93 (1H, s), 7.10 (1H, d, J = 8.5 Hz),
7.20-7.40 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-acetamide-4- (N, N'-bis-t-butyl
(Xycarbonylguanidino) -9-O-hexanoyl-
2,3,4,5,7-pentadeoxy-7-fluoro-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 13 (i) (50 mg, 0.072 mmo
l) was dissolved in methylene chloride (2 ml) and triethylamine (11 mg, 0.11 mmol) and hexanoyl chloride (11 m
g, 0.086 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (47 mg, 83
%). Rf = 0.6 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -4.0 ° (c = 0.1, CHCl 3); MS (FAB) m / e 786 (M + + H); 1 H- NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.90 (3H, m), 1.
20-1.40 (6H, m), 1.48 (9H, s), 1.50 (9H, s), 1.97
(3H, s), 2.35 (2H, t, J = 7.5 Hz), 2.95 (1H, d, J
= 5.0 Hz), 4.20-4.60 (6H, m), 5.25 (1H, m), 5.97
(1H, d, J = 2.6Hz), 6.65 (1H, d, J = 8.5Hz), 6.93
(1H, s), 7.20-7.40 (10H, m), 8.60 (1H, d, J = 8.5
(Iii) 5-acetamido-4-guanidino-9-O-hex.
Sanoyl-2,3,4,5,7-pentadeoxy-7-
Fluoro-D-glycero-D-galacto-non-2-e
Nopyranosonic acid trifluoroacetate Compound obtained in Example 13 (ii) (40 mg, 0.05 mmol)
With a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (18 mg, 65).
%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 60.0 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 433 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (3H,
m), 1.25-1.40 (4H, m), 1.55-1.70 (2H, m), 2.00 (3H,
s), 2.35 (2H, t, J = 4.5 Hz), 4.10-4.40 (5H, m),
4.45-4.70 (2H, m), 5.60 (1H, d, J = 2.4 Hz). (Example 14) 5-Acetamide-4-guanidino-9-O-octanoy
-2,3,4,5,7-pentadeoxy-7-fluoro
B-D-Glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 1-3
8) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
(Xycarbonylguanidino) -9-O-octanoyl-
2,3,4,5,7-pentadeoxy-7-fluoro-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 13 (i) (50 mg, 0.072 mmo
l) was dissolved in methylene chloride (2 ml) and triethylamine (11 mg, 0.11 mmol) and octanoyl chloride (16 m
g, 0.086 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (45 mg, 77
%). Rf = 0.5 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -5.2 ° (c = 0.2, CHCl 3); MS (FAB) m / e 814 (M + + H); 1 H- NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.48 (9H, s), 1.
50 (9H, s), 1.95 (3H, s), 3.65 (1H, dd, J = 5.0, 1
8 Hz), 3.80 (1H, dd, J = 1.8, 18 Hz), 4.15 (1H,
m), 4.23 (1H, d, J = 8.5 Hz), 4.30-4.60 (3H, m),
5.95 (1H, d, J = 2.3 Hz) (ii) 5-acetamido-4-guanidino-9-O-octa
Noyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 14 (i) (40 mg, 0.05 mmol)
With a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. After completion of the reaction, the solvent was distilled off, and the residue was subjected to silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate:
Water) to give the title compound as a colorless solid (18
mg, 64%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 56 ° (c = 0.2, CH ₃ OH); MS (FAB) m / e 461 ( M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (3
H, m), 1.25-1.40 (8H, m), 1.55-1.70 (2H, m), 2.00
(3H, s), 2.35 (2H, t, J = 4.5 Hz), 4.10-4.40 (5H,
m), 4.45-4.70 (2H, m), 5.60 (1H, d, J = 2.4 Hz). (Example 15) 5-Acetamide-4-guanidino-9-O-dodecanoy
-2,3,4,5,7-pentadeoxy-7-fluoro
B-D-Glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 1-4
0) (i) 5-acetamido-4- (N, N'-bis-t-butylo)
(Xycarbonylguanidino) -9-O-dodecanoyl-
2,3,4,5,7-pentadeoxy-7-fluoro-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 13 (i) (55 mg, 0.078 mmo
l) was dissolved in methylene chloride (2 ml) and triethylamine (10 mg, 0.10 mmol) and dodecanoyl chloride (21 m
g, 0.094 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogencarbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (1: 1 = ethyl acetate: hexane) to give the title compound as a colorless amorphous (48 mg, 69%).

[0335] Rf = 0.4 (1: 1 = ethyl acetate: ^{_{hexane); [α] D 25 =}} -5.7 ° (c = 0.12, CHCl 3); MS (FAB) m / e 883 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.90 (3H, m), 1.
20-1.40 (18H, m), 1.48 (9H, s), 1.50 (9H, s), 1.97
(3H, s), 2.35 (2H, t, J = 7.5 Hz), 2.95 (1H, d, J
= 5.0 Hz), 4.20-4.60 (6H, m), 5.25 (1H, m), 5.97
(1H, d, J = 2.6Hz), 6.65 (1H, d, J = 8.5Hz), 6.93
(1H, s), 7.20-7.40 (10H, m), 8.60 (1H, d, J = 8.5
(Ii) 5-acetamido-4-guanidino-9-O-dodeca
Noyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 15 (i) (43 mg, 0.05 mmol)
With a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (33 mg, 91
%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 22.7 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 517 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (3H,
m), 1.25-1.40 (16H, m), 1.55-1.70 (2H, m), 2.00 (3
H, s), 2.35 (2H, t, J = 7.0 Hz), 4.10-4.40 (5H,
m), 4.45-4.70 (2H, m), 5.60 (1H, d, J = 2.4 Hz). (Example 16) 5-Acetamide-4-guanidino-9-O-myristoy
-2,3,4,5,7-pentadeoxy-7-fluoro
B-D-Glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 1-4
1) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
(Xycarbonylguanidino) -9-O-myristoyl-
2,3,4,5,7-pentadeoxy-7-fluoro-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 13 (i) (50 mg, 0.072 mmo
l) was dissolved in methylene chloride (2 ml), triethylamine (11 mg, 0.11 mmol), myristoyl chloride (21 mg)
, 0.086 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (50 mg, 77
%).

[0337] Rf = 0.4 (1: 1 = ethyl acetate: ^{_{hexane); [α] D 25 =}} -7.0 ° (c = 0.10, CHCl 3); MS (FAB) m / e 898 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.90 (3H, m), 1.
20-1.40 (22H, m), 1.48 (9H, s), 1.50 (9H, s), 1.97
(3H, s), 2.35 (2H, t, J = 7.5 Hz), 2.95 (1H, d, J
= 5.0 Hz), 4.20-4.60 (6H, m), 5.25 (1H, m), 5.97
(1H, d, J = 2.6Hz), 6.65 (1H, d, J = 8.5Hz), 6.93
(1H, s), 7.20-7.40 (10H, m), 8.60 (1H, d, J = 8.5
(Ii) 5-acetamido-4-guanidino-9-O-myris
Toyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 16 (i) (40 mg, 0.05 mmol)
With a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (21 mg, 64
%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 22.0 ° (c = 0.06, CH ₃ OH); MS (FAB) m / e 545 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.8
5-0.95 (3H, m), 1.25-1.70
(20H, m), 1.55-1.70 (2H,
m), 2.00 (3H, s), 2.35 (2
H, t, J = 4.5 Hz), 4.10−
4.40 (5H, m), 4.45-4.70
(1H, m), 5.60 (1H, d, J =
2.4 Hz). Example 17 5-Acetamide-4-guanidino-9-O-hexadeca
Noyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate (Exemplary Compound No. 1
-42) (i) 5-acetamide-4- (N, N'-bis-t-butyi )
Ruoxycarbonylguanidino) -9-O-hexadeca
Noyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Diphenylmethyl pyranosonate The compound obtained in Example 13 (i) (58 mg, 0.08 mmol)
) Was dissolved in methylene chloride (2 ml) and triethylamine (10 mg, 0.10 mmol) and palmitoyl chloride (26 m
g, 0.0946 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (1: 1 = ethyl acetate: hexane) to give the title compound as a colorless amorphous (50 mg, 67%).

[0339] Rf = 0.4 (1: 1 = ethyl acetate: ^{_{hexane); [α] D 25 =}} -11.0 ° (c = 0.11, CHCl 3); MS (FAB) m / e 939 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.90 (3H, m), 1.2
0-1.40 (22H, m), 1.48 (9H, s), 1.50 (9H, s), 1.97
(3H, s), 2.35 (2H, t, J = 7.5 Hz), 2.95 (1H, d, J
= 5.0 Hz), 4.20-4.60 (6H, m), 5.25 (1H, m), 5.97
(1H, d, J = 2.6 Hz), 6.65 (1H, d, J = 8.5 Hz), 6.93
(1H, s), 7.20-7.40 (10H, m), 8.60 (1H, d, J = 8.5
(Ii) 5-acetamido-4-guanidino-9-O-hexa ).
Decanoyl-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Enopyranosonic acid trifluoroacetate Compound obtained in Example 17 (i) (45 mg, 0.05 mmol)
With a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (28 mg, 73
%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 19.7 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 573 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (3H,
m), 1.25-1.40 (16H, m), 1.55-1.70 (2H, m), 2.00 (3
H, s), 2.35 (2H, t, J = 7.0 Hz), 4.10-4.40 (5H,
m), 4.45-4.70 (2H, m), 5.60 (1H, d, J = 2.4 Hz). (Example 18) 5-acetamido-4-guanidino-9-O-octadeca
Noyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate (Exemplary Compound No. 1
-43) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
(Xycarbonylguanidino) -9-O-octadecanoi
-2,3,4,5,7-pentadeoxy-7-fluoro
B-D-Glycero-D-galacto-non-2-enopyra
Diphenylmethyl nosonate The compound obtained in Example 13 (i) (55 mg, 0.08 mmol)
Was dissolved in methylene chloride (2 ml), triethylamine (10 mg, 0.10 mmol) and stearoyl chloride (29 mg, 0.094 mmol) were added under ice-cooling, and the mixture was stirred at 0 ° C for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (1: 1 = ethyl acetate: hexane) to give the title compound as a colorless amorphous (51 mg, 67%).

[0341] Rf = 0.5 (1: 1 = ethyl acetate: ^{_{hexane); [α] D 25 =}} -8.1 ° (c = 0.16, CHCl 3); MS (FAB) m / e 967 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.90 (3H, m),
1.20-1.40 (30H, m), 1.48 (9H, s), 1.50 (9H, s), 1.9
7 (3H, s), 2.35 (2H, t, J = 7.5 Hz), 2.95 (1H, d, J
= 5.0 Hz), 4.20-4.60 (6H, m), 5.25 (1H, m), 5.97
(1H, d, J = 2.6 Hz), 6.65 (1H, d, J = 8.5 Hz), 6.93
(1H, s), 7.20-7.40 (10H, m), 8.60 (1H, d, J = 8.5
(Ii) 5-acetamido-4-guanidino-9-O-octa.
Decanoyl-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Enopyranosonic acid trifluoroacetate Compound obtained in Example 18 (i) (45 mg, 0.047 mmo
l) was dissolved in a mixture of methylene chloride and trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours.
The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (24 mg, 6 mg).
2%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 14.3 ° (c = 0.15, CH ₃ OH); MS (FAB) m / e 601 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (3H,
m), 1.25-1.40 (28H, m), 1.55-1.70 (2H, m), 2.00 (3
H, s), 2.35 (2H, t, J = 7.0 Hz), 4.10-4.40 (5H,
m), 4.45-4.70 (2H, m), 5.60 (1H, d, J = 2.4 Hz). (Example 19) 5-acetamido-4-guanidino-8,9-di-OA
Cetyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate (Exemplary Compound No. 1
-54) (i) 5-acetamido-4- (N, N'-bis-t-butylo
Xycarbonylguanidino) -8,9-di-O-acetyl
2,3,4,5,7-pentadeoxy-7-fluoro
B-D-Glycero-D-galacto-non-2-enopyra
Diphenylmethyl nosonate The compound obtained in Example 13 (i) (58 mg, 0.083 mmo
l) in pyridine (2 ml) and acetic anhydride (0.5 ml)
Was added under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a 1N aqueous hydrochloric acid solution (3 ml). The solvent was distilled off. The residue was purified by silica gel chromatography (1: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (59 mg, 91
%).

[0343] Rf = 0.47 (1: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} +2.5 ° (c = 0.12, CHCl 3); MS (FAB) m / e 785 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.48 (9H, s), 1.
49 (9H, s), 1.99 (3H, s), 2.04 (3H, s), 2.07 (3H,
s), 4.00-4.30 (3H, m), 4.75 (1H, d, J = 13 Hz),
4.80 (1H, dd, J = 7.5, 45 Hz), 5.20 (1H, ddd, J =
1.0, 9.0, 9.0Hz), 5.50 (1H, m), 5.92 (1H, d, J =
2.4 Hz), 6.72 (1H, d, J = 7.5 Hz), 6.94 (1H, s),
7.20-7.50 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-acetamido-4-guanidino-8, 9-di-O
-Acetyl-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Enopyranosonic acid trifluoroacetate Compound obtained in Example 19 (i) (50 mg, 0.064 mmo
l) was dissolved in a mixture of methylene chloride and trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours.
The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (23 mg, 5 mg).
6%).

Rf = 0.16 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 36.9 ° (c = 0.15, CH ₃ OH); MS (FAB) m / e 419 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 2.00 (3H, s),
2.03 (3H, s), 2.05 (3H, s), 4.10-4.40 (4H, m),
4.70-5.00 (2H, m), 5.50 (1H, m), 5.70 (1H, d, J =
(Example 20) 5-Acetamide-4-guanidino-8,9-di-O-oop
Lopionyl-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galactonone-2-
Enopyranosonic acid trifluoroacetate (Exemplified Compound No. 1-55) (i) 5-acetamido-4- (N, N'-bis-t-butylo)
(Xycarbonylguanidino) -8,9-di-O-propyl
Onyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Diphenylmethyl pyranosonate The compound obtained in Example 13 (i) (52 mg, 0.074 mmo
l) was dissolved in pyridine (2 ml), propionacetic anhydride (0.5 ml) was added under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The reaction solution was treated with ethyl acetate (5 ml) and 1N hydrochloric acid aqueous solution (3 ml).
And the organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and then with a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (1: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (54 mg, 90%).

[0345] Rf = 0.54 (1: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} +9.6 ° (c = 0.14, CHCl 3); MS (FAB) m / e 813 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.11 (9H, t,
7.5 Hz), 1.48 (9H, s), 1.49 (9H, s), 2.04 (3H, s),
2.20-2.35 (4H, m), 4.00-4.30 (3H, m), 4.75 (1H, d,
J = 13 Hz), 4.80 (1H, dd, J = 7.5, 45 Hz), 5.20
(1H, ddd, J = 1.0, 9.0, 9.0 Hz), 5.50 (1H, m), 5.92
(1H, d, J = 2.4 Hz), 6.72 (1H, d, J = 7.5 Hz), 6.94
(1H, s), 7.20-7.50 (10H, m), 8.60 (1H, d, J = 8.5
(Ii) 5-acetamido-4-guanidino-8,9-di-O
-Propionyl-2,3,4,5,7-pentadeoxy
-7-Fluoro-D-glycero-D-galacto-non-
2-Enopyranosonic acid trifluoroacetate Compound obtained in Example 20 (i) (46 mg, 0.057 mmol
l) was dissolved in a mixture of methylene chloride and trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours.
The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (24 mg, 6 mg).
3%).

Rf = 0.25 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 32.3 ° (c = 0.14, CH ₃ OH); MS (FAB) m / e 447 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 1.10 (6H, t, J
= 7.5), Hz 2.00 (3H, s), 2.35 (4H, q, J = 7.5),
4.10-4.40 (4H, m), 4.70-5.00 (2H, m), 5.50 (1H,
m), 5.60 (1H, d, J = 3.0 Hz). (Example 21) (ii) 5-Acetamide-4-guanidino-8,9-di-O
-Hexanoyl-2,3,4,5,7-pentadeoxy
-7-Fluoro-D-glycero D-galacto-non-
2-enopyranosonic acid trifluoroacetate (Exemplary Compound No. 1-58) (i) 5-acetamido-4- (N, N'-bis-t-butylo)
(Xycarbonylguanidino) -8,9-di-O-hexa
Noyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Diphenylmethyl pyranosonate The compound obtained in Example 13 (i) (44 mg, 0.063 mmo
l) was dissolved in methylene chloride (2 ml), 4-dimethylaminopyridine (19 mg, 0.17 mmol) and hexanoyl chloride (19 mg, 0.14 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine and dried over anhydrous sodium sulfate.
The solvent was distilled off. The residue was purified by silica gel chromatography (3: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (49 mg, 87%).

[0347] Rf = 0.28 (3: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} +6.5 ° (c = 0.10, CHCl 3); MS (FAB) m / e 897 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-1.00 (6H,
m), 1.20-1.40 (8H, m), 1.48 (9H, s), 1.49 (9H, s),
1.50-1.70 (4H, m), 1.98 (3H, s), 2.20-2.30 (4H, m),
4.00-4.30 (3H, m), 4.75 (1H, d, J = 13 Hz), 4.80
(1H, dd, J = 7.4, 45 Hz), 5.18 (1H, ddd, J = 1.0,
9.0, 9.0 Hz), 5.50 (1H, m), 5.93 (1H, d, J = 2.4 H
z), 6.70 (1H, d, J = 7.5 Hz), 6.93 (1H, s), 7.20-
7.50 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-acetamido-4-guanidino-8, 9-di-O
-Hexanoyl-2,3,4,5,7-pentadeoxy
-7-Fluoro-D-glycero-D-galacto-non-
2-Enopyranosonic acid trifluoroacetate Compound obtained in Example 21 (i) (42 mg, 0.047 mmo
l) as a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (21 mg, 59).
%).

Rf = 0.34 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 23.7 ° (c = 0.11, CH ₃ OH); MS (FAB) m / e 531 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (6H,
m), 1.20-1.40 (8H, m), 1.55-1.70 (4H, m), 2.00 (3
H, s), 2.30 (2H, t, J = 7.5 Hz), 4.10-4.40 (4H,
m), 4.70-5.00 (2H, m), 5.55 (1H, m), 5.65 (1H, d,
(J = 3.0 Hz). (Example 22) 5-Acetamide-4-guanidino-8,9-di-O-de
Canoyl-2,3,4,5,7-pentadeoxy-7-
Fluoro-D-glycero-D-galacto-non-2-e
Nopyranosonic acid trifluoroacetate (Exemplary Compound No. 1
-61) (i) 5-acetamide-4- (N, N'-bis-t-butylo
Xycarbonyl guanidino) -8,9-di-O-decano
Yl-2,3,4,5,7-pentadeoxy-7-fur
Oro-D-glycero-D-galacto-non-2-enopi
Diphenylmethyl lanosonate The compound obtained in Example 13 (i) (42 mg, 0.06 mmol
Was dissolved in methylene chloride (2 ml), 4-dimethylaminopyridine (18 mg, 0.15 mmol) and decanoyl chloride (26 mg, 0.14 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (3: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (52 mg, 86
%).

[0349] Rf = 0.28 (3: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} + 13.3 ° (c = 0.17, CHCl 3); MS (FAB) m / e 1009 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.90 (6H,
m), 1.20-1.40 (24H, m), 1.48 (9H, s), 1.49 (9H, s),
1.50-1.65 (4H, m), 1.98 (3H, s), 2.20-2.30 (4H,
m), 4.00-4.30 (3H, m), 4.75 (1H, d, J = 13 Hz), 4.
80 (1H, dd, J = 7.5, 45 Hz), 5.20 (1H, ddd, J = 1.
0, 9.0, 9.0 Hz), 5.50 (1H, m), 5.92 (1H, d, J = 2.4
Hz), 6.65 (1H, d, J = 7.5 Hz), 6.93 (1H, s), 7.20-
7.50 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-acetamido-4-guanidino-8, 9-di-O
-Decanoyl-2,3,4,5,7-pentadeoxy-
7-fluoro-D-glycero-D-galacto-non-2
-Enopyranosonic acid trifluoroacetate Compound obtained in Example 22 (i) (45 mg, 0.045 mmo
l) as a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (29 mg, 75
%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 20.6 ° (c = 0.14, CH ₃ OH); MS (FAB) m / e 643 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (6H,
m), 1.20-1.40 (24H, m), 1.55-1.70 (4H, m), 2.00 (3
H, s), 2.30 (2H, t, J = 7.0 Hz), 4.10-4.40 (4H, m),
4.70-5.00 (2H, m), 5.55 (1H, m), 5.70 (1H, d, J =
3.0 Hz). (Example 23) 5-Acetamide-4-guanidino-8,9-di-O-mi
Ristoyl-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Enopiranoson acid trifluoroacetate (Compound No. 1-63) (i) 5-acetamido-4-(N, N'-bis -t - Buchiruo
(Xycarbonylguanidino) -8,9-di-O-myris
Toyl-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Diphenylmethyl pyranosonate The compound obtained in Example 13 (i) (43 mg, 0.06 mmol
Was dissolved in methylene chloride (2 ml), 4-dimethylaminopyridine (19 mg, 0.15 mmol) and myristoyl chloride (26 mg, 0.14 mmol) were added under ice-cooling, and the solution was added at room temperature.
Stirred for hours. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (3: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (60 m
g, 87%).

[0351] Rf = 0.28 (3: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} + 15.5 ° (c = 0.11, CHCl 3); MS (FAB) m / e 1121 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.90 (6H,
m), 1.20-1.40 (40H, m), 1.48 (9H, s), 1.49 (9H, s),
1.50-1.65 (4H, m), 1.98 (3H, s), 2.20-2.30 (4H,
m), 4.00-4.30 (3H, m), 4.75 (1H, d, J = 13 Hz), 4.
80 (1H, dd, J = 7.5, 45 Hz), 5.18 (1H, ddd, J = 1.
0, 9.0, 9.0 Hz), 5.50 (1H, m), 5.93 (1H, d, J = 2.4
Hz), 6.66 (1H, d, J = 7.5 Hz), 6.93 (1H, s), 7.20-
7.50 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-acetamido-4-guanidino-8,9-di-O
-Myristoyl-2,3,4,5,7-pentadeoxy
-7-Fluoro-D-glycero-D-galacto-non-
2-enopyranosonic acid trifluoroacetate The compound obtained in Example 23 (i) (52 mg, 0.046 mmo
l) was dissolved in a mixture of methylene chloride and trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours.
The solvent was distilled off and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (38 mg, 8
3%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 28.0 ° (c = 0.16, CH ₃ OH); MS 755 (FAB) m / e ^{545 (M + + H);} 1 H-NMR (CD 3 OD, 270 MHz) δ (ppm): 0.85-0.95 (6H,
m), 1.20-1.40 (40H, m), 1.55-1.70 (4H, m), 2.00 (3
H, s), 2.30 (2H, t, J = 7.0 Hz), 4.10-4.40 (4H,
m), 4.70-5.00 (2H, m), 5.55 (1H, m), 5.70 (1H, d,
(J = 3.0 Hz). (Example 24) 5-Acetamide-4-guanidino-8,9-di-O-he
Xadecanoyl-2,3,4,5,7-pentadeoxy
-7-Fluoro-D-glycero-D-galacto-non-
2-enopyranosonic acid trifluoroacetate (Exemplary Compound No. 1-64) (i) 5-acetamido-4- (N, N′-bi)
S-tert-butyloxycarbonylguanidino) -8,9
-Di-O-hexadecanoyl-2,3,4,5,7-pe
Ntadeoxy-7-fluoro-D-glycero-D-gala
Diphenylmethyl ct-non-2-enopyranosonate The compound obtained in Example 13 (i) (37 mg, 0.053 mmol)
l) was dissolved in methylene chloride (2 ml), 4-dimethylaminopyridine (16 mg, 0.13 mmol) and hexadecanoyl chloride (34 mg, 0.12 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml).
The organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (3: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (52 mg, 84
%).

[0353] Rf = 0.3 (3: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} + 10.9 ° (c = 0.11, CHCl 3); MS (FAB) m / e 1177 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.90 (6H,
m), 1.20-1.40 (48H, m), 1.48 (9H, s), 1.49 (9H, s),
1.50-1.65 (4H, m), 1.98 (3H, s), 2.20-2.30 (4H,
m), 4.00-4.30 (3H, m), 4.75 (1H, d, J = 13 Hz), 4.
80 (1H, dd, J = 7.5, 45 Hz), 5.20 (1H, ddd, J = 1.
0, 9.0, 9.0 Hz), 5.50 (1H, m), 5.92 (1H, d, J = 2.4
Hz), 6.65 (1H, d, J = 7.5 Hz), 6.93 (1H, s), 7.20-
7.50 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-acetamido-4-guanidino-8,9-di-O
-Hexadecanoyl-2,3,4,5,7-pentadeo
Xy-7-fluoro-D-glycero-D-galacto-no
2-Enopyranosonic acid trifluoroacetate Compound obtained in Example 24 (i) (42 mg, 0.036 mmo
l) was dissolved in a mixture of methylene chloride and trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours.
The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (22 mg, 5 mg).
9%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 15.3 ° (c = 0.11, CH ₃ OH); MS (FAB) m / e 811 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (6H,
m), 1.20-1.40 (48H, m), 1.55-1.70 (4H, m), 2.00 (3
H, s), 2.30 (2H, t, J = 7.0 Hz), 4.10-4.40 (4H,
m), 4.70-5.00 (2H, m), 5.55 (1H, m), 5.70 (1H, d,
(J = 3.0 Hz). (Example 25) 5-Acetamide-4-guanidino-8,9-di-O-O
Kutadecanoyl-2,3,4,5,7-pentadeoxy
-7-Fluoro-D-glycero-D-galacto-non-
2-enopyranosonic acid trifluoroacetate (Exemplified Compound No. 65-1) (i) 5-acetamido-4- (N, N'-bis-t-butylo)
(Oxycarbonylguanidino) -8,9-di-O-octa
Decanoyl-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Diphenylmethyl enopyranosonate The compound obtained in Example 13 (i) (35 mg, 0.05 mmol)
Was dissolved in methylene chloride (2 ml), triethylamine (15 mg, 0.13 mmol) and octadecanoyl chloride (35 mg, 0.115 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (3: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (57 mg, 93
%).

[0355] Rf = 0.3 (3: 1 = hexane: ethyl ^{_{acetate); [α] D 25 =}} + 11.2 ° (c = 0.18, CHCl 3); MS (FAB) m / e 1233 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.90 (6H,
m), 1.20-1.40 (56H, m), 1.48 (9H, s), 1.49 (9H,
s), 1.50-1.65 (4H, m), 1.98 (3H, s), 2.20-2.30 (4
H, m), 4.00-4.30 (3H, m), 4.75 (1H, d, J = 13 Hz),
4.80 (1H, dd, J = 7.5, 45 Hz), 5.20 (1H, ddd, J =
1.0, 9.0, 9.0 Hz), 5.50 (1H, m), 5.92 (1H, d, J =
2.4 Hz), 6.65 (1H, d, J = 7.5 Hz), 6.93 (1H, s),
7.20-7.50 (10H, m), 8.60 (1H, d, J = 8.5 Hz). (Ii) 5-Acetamide-4-guanidino-8,9-di-O
-Octadecanoyl-2,3,4,5,7-pentadeo
Xy-7-fluoro-D-glycero-D-galacto-no
2-enopyranosonic acid trifluoroacetate Compound obtained in Example 25 (i) (47 mg, 0.04 mmol)
With a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (28 mg, 67).
%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 14.5 ° (c = 0.14, CH ₃ OH); MS (FAB) m / e 867 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.85-0.95 (6H,
m), 1.20-1.40 (56H, m), 1.55-1.70 (4H, m), 2.00
(3H, s), 2.30 (2H, t, J = 7.0 Hz), 4.10-4.40 (4H,
m), 4.70-5.00 (2H, m), 5.55 (1H, m), 5.70 (1H, d,
(J = 3.0 Hz). (Example 26) 5-Acetamide-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-fluoro-D-glycero-D-
Hexadecyl galacto-non-2-enopyranosonic acid
Lifluoroacetate (Exemplified Compound No. 1-6) (i) 5-Acetamide-4-azido-8,9-O-isoprop
Lopylidene-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Hexadecyl enopyranosonate The compound obtained in Example 7 (i) (275 mg, 0.74 mmol)
Was dissolved in methanol: water (6: 1) (7 ml), 1M aqueous potassium hydroxide solution (0.82 ml) was added, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off, followed by drying under reduced pressure at room temperature for 2 hours to obtain a pale yellow solid. This solid was dissolved in acetonitrile (8 ml), and 18-crown-6 (195 mg, 0.74 mml) and hexadecyl bromide (677 mg, 2.2 mmol) were added.
Stirred at 30 ° C. for 30 minutes. After completion of the reaction, the solvent was distilled off, and a two-layer solution of ethyl acetate (15 ml) and a saturated aqueous solution of sodium hydrogen carbonate (10 ml) was poured into the obtained residue. The organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. And the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (240
mg, 56%).

[0357] Rf = 0.50 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 65.0 ° (c = 0.5, CHCl 3); MS (FAB) m / e 583 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.95 (3H,
m), 1.20-1.40 (28H, m), 1.37 (3H, s), 1.42 (3H,
s), 1.60-1.80 (2H, m), 2.05 (3H, s), 4.10-4.30 (3
H, m), 4.40 (1H., M), 4.72 (1H, ddd, J = 1.3, 5.
3, 47.0 Hz), 4.90 (1H, dd, J = 2.4, 9.3 Hz), 4.92
(1H, ddd, J = 1.4, 10.0, 28.0 Hz), 5.92 (1H, d, J
= 7.2 Hz), 5.94 (1H, d, J = 2.6 Hz). (Ii) 5-acetamido-4- (N, N'-bis-t-butylo
(Oxycarbonylguanidino) -8,9-O-isopropyl
Riden-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Hexadecyl pyranosonate The compound obtained in Example 26 (i) (240 mg, 0.41 mmol
Was dissolved in methanol (10 ml), a Lindlar catalyst (60 mg) was added, and the mixture was stirred under a hydrogen atmosphere for 2 hours. The catalyst was filtered off and the solvent was distilled off. The residue was dissolved in dimethylformamide (4 ml), N, N- di -t- butoxycarbonyl thiourea (145 mg, 0.53 mmol), triethylamine (106 mg, 1.05 mg) and mercuric chloride (HgCl ₂₎ (14
2 mg, 0.53 mg) and stirred at room temperature for 1 hour. The solid was filtered off, the filtrate was poured into a two-layer solution of ethyl acetate (15 ml) and a saturated aqueous solution of sodium hydrogen carbonate (10 ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and dried. Was distilled off. The residue was purified by silica gel chromatography (1: 2 = ethyl acetate: hexane) to give the title compound as a colorless syrup (220 mg, 67
%).

[0358] Rf = 0.40 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = -11.6 ° (c = 0.06, CHCl 3); MS (FAB) m / e 799 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.95 (3H,
m), 1.20-1.40 (28H, m), 1.37 (3H, s), 1.41 (3H,
s), 1.49 (9H, s), 1.50 (9H, s), 1.60-1.80 (2H, m),
1.97 (3H, s), 4.10-4.30 (4H, m), 4.40-4.65 (2H,
m), 5.20 (1H, ddd, J = 2.4, 7.5, 7.5 Hz), 5.83 (1
H, d, J = 2.4 Hz), 5.65 (1H, d, J = 7.0 Hz), 8.60
(1H, d, J = 8.5 Hz). (Iii) 5-Acetamide-4-guanidino-2,3,4
5,7-pentadeoxy-7-fluoro-D-glycero
-D-galacto-non-2-enopyranosonic acid hexade
Sil trifluoroacetate Compound obtained in Example 26 (ii) (200 mg, 0.25 mmol)
Is a mixture of methylene chloride and trifluoroacetic acid (3: 1)
(10 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2: 8:
Purification with 1 = 2-propanol: ethyl acetate: water) afforded the title compound as a colorless solid (130 mg, 77%).

Rf = 0.55 (5: 1: 1 = t-butanol: acetic acid: water); [α] _D ²⁵ = + 14.7 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 559 ( M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 0.70-0.85 (3H, m),
1.10-1.30 (28H, m), 1.60-1.80 (2H, m), 2.00 (3H,
s), 3.60-3.85 (2H, m), 4.00-4.30 (3H, m) 4.50-4.80
(2H, m), 5.88 (1H, s). Example 27 5-Acetamide-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-fluoro-D-glycero-D-
Galacto-non-2-enopyranosonic acid stearyl ester
Lifluoroacetate (Exemplified Compound No. 1-7) (i) 5-Acetamide-4-azido-8,9-O-isoprop
Lopylidene-2,3,4,5,7-pentadeoxy-7
-Fluoro-D-glycero-D-galacto-non-2-
Stearyl enopyranosonate The compound obtained in Example 7 (i) (45 mg, 0.12 mmol)
Was dissolved in a mixture of methanol and water (6: 1) (4 ml), a 1M aqueous solution of potassium hydroxide (0.13 ml) was added, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off, followed by drying under reduced pressure at room temperature for 2 hours to obtain a pale yellow solid. This solid was dissolved in acetonitrile (2 ml) and 18-crown-6 (32 mg, 0.12
ml) and stearyl bromide (121 mg, 0.36 mmol) were added, and the mixture was stirred at 80 ° C for 30 minutes. The residue was treated with ethyl acetate (7
ml) and a saturated aqueous solution of sodium hydrogen carbonate (5 ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (2: 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (42 mg, 58%).

[0360] Rf = 0.50 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 76 ° (c = 0.05, CHCl 3); MS (FAB) m / e 611 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85-0.95 (3H,
m), 1.20-1.40 (32H, m), 1.37 (3H, s), 1.42 (3H,
s), 1.60-1.80 (2H, m), 2.05 (3H, s), 4.10-4.30 (3
H, m), 4.40 (1H., M), 4.72 (1H, ddd, J = 1.3, 5.
3, 47.0 Hz), 4.90 (1H, dd, J = 2.6, 9.5 Hz), 4.92
(1H, ddd, J = 1.4, 10.0, 28.0 Hz), 5.94 (1H, d, J
= 7.2 Hz), 5.91 (1H, d, J = 2.6 Hz). (Ii) 5-Acetamide-4- (N, N'-bis-t-butylo
(Oxycarbonylguanidino) -8,9-O-isopropyl
Riden-2,3,4,5,7-pentadeoxy-7-fu
Fluoro-D-glycero-D-galacto-non-2-eno
Stearyl pyranosonate The compound obtained in Example 27 (i) (40 mg, 0.066 mmo
l) was dissolved in methanol (3 ml), a Lindlar catalyst (10 mg) was added, and the mixture was stirred under a hydrogen atmosphere for 2 hours. The catalyst was filtered off and the solvent was distilled off. The residue was dissolved in dimethylformamide (2 ml), N, N'- di -t- butoxycarbonyl thiourea (25 mg, 0.09 mmol), triethylamine (18 mg, 0.18 mg) and mercuric chloride (HgCl ₂₎ ( twenty five
mg, 0.09 mmol) and stirred at room temperature for 1 hour. The resulting solid was filtered off, the filtrate was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off. The residue was purified by silica gel chromatography (1: 1 = hexane: ethyl acetate) to give the title compound as a colorless syrup (39 mg)
, 71%).

[0361] Rf = 0.40 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = -7.4 ° (c = 0.10, CHCl 3); MS (FAB) m / e 827 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.80-0.95 (3H,
m), 1.20-1.40 (32H, m), 1.37 (3H, s), 1.41 (3H,
s), 1.49 (9H, s), 1.50 (9H, s), 1.60-1.80 (2H, m),
1.97 (3H, s), 4.10-4.30 (4H, m), 4.40-4.65 (2H,
m), 5.20 (1H, ddd, J = 2.4, 7.5, 7.5 Hz), 5.83 (1
H, d, J = 2.3 Hz), 5.65 (1H, d, J = 7.0 Hz), 8.60
(1H, d, J = 8.5 Hz). (Iii) 5-Acetamide-4-guanidino-2,3,4
5,7-pentadeoxy-7-fluoro-D-glycero
-D-galacto-non-2-enopyranosonic acid stearie
Trifluoroacetate Compound obtained in Example 27 (ii) (30 mg, 0.04 mmol)
Was dissolved in a mixture (3 ml) of methylene chloride and trifluoroacetic acid (3: 1), and the mixture was stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2: 8:
Purification with 1 = 2-propanol: ethyl acetate: water) afforded the title compound as a colorless solid (20 mg, 79%).

Rf = 0.55 (5: 1: 1 = butanol: acetic acid: water); [α] _D ²⁵ = + 14.0 ° (c = 0.10, CH ₃ OH); MS (FAB) m / e 587 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 0.70-0.85 (3H,
m), 1.10-1.30 (32H, m), 1.60-1.80 (2H, m), 2.00 (3
H, s), 3.60-3.85 (2H, m), 4.00-4.30 (3H, m) 4.50-
4.80 (2H, m), 5.88 (1H, s). (Example 28) 5-Acetamide-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-methoxy-D-glycero-D-
Galacto-non-2-enopyranosonic acid trifluoro
Acetate (Exemplified Compound No. 163-1) (i) Benzyl N-acetyl-3,6-di-O-benzyl
4-O-methyl-α-D-glucosamine Carbohydrate Res. 83 , 163-1
69 (1980). Benzyl N-acetyl-3,6-di-O-benzyl-α
-D-Glucosamine (4.48 g, 9.12 mmol) was dissolved in dimethylformamide (50 ml), and sodium hydride (1.0 g
, 22.5 mmol) and stirred at room temperature for 30 minutes. Then, methyl iodide (1.42 g, 100 mmol) was added at 0 ° C., and the mixture was stirred at room temperature for 5 hours. The reaction solution was treated with ethyl acetate (100
ml) and saturated aqueous sodium hydrogen carbonate solution (50 ml).
The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (4: 1 = methylene chloride: ethyl acetate) to give the title compound as a colorless solid (3.6 g, 78%).

[0363] Rf = 0.55 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} +126 ° (c = 1.15, CHCl 3); MS (FAB) m / e 506 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.80 (3H, s),
3.48 (3H, s), 3.40-3.80 (5H, m), 4.23 (1H, ddd, J
= 3.5, 10.0, 10.0 Hz), 4.40-4.90 (7H, m), 5.25 (1
(H, d, J = 10.0 Hz), 7.20-7.40 (15H, m). (Ii) N-acetyl-4-O-methyl-α-D-glucosa
The compound obtained in Example 28 (i) (3.6 g, 7.12 mmol)
) Was dissolved in acetic acid (40 ml), and palladium on carbon (5.0
g) was added and the mixture was stirred under a hydrogen atmosphere of 3 atm for 30 hours.
The catalyst was removed by filtration, the solvent was distilled off, and the residue was purified by silica gel chromatography (10: 1 to 5: 1 = methylene chloride: methanol) to obtain the title compound as a colorless solid (1.42 g, 83%). ).

[0364] Rf = 0.35 (5: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 72.2 ° (c = 2.9, CH 3 OH); MS (FAB) m / e 236 (M + + H) ; ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 1.98 (3H, s),
3.57 (3H, s), 3.60-3.80 (6H, m), 5.05 (1H, d, J =
3.2 Hz). (Iii) 5-Acetamide-3,5-dideoxy-7-O-
Methyl-D-glycero-D-galact-2-nonulopyra
Nosonic acid The compound obtained in Example 28 (ii) (5.0 g, 21.3 mmol)
Was dissolved in distilled water, and sodium azide (100 mg) and sodium pyruvate (5.0 g, 45.5 mmol) were added.
The pH of the reaction solution was adjusted to 1 using an N sodium hydroxide aqueous solution.
0 to 11. Then, 25 mg (660 U) of N-acetyl-neuraminic acid aldolase (manufactured by TOYOBO) was added, and 2
Stirred at 0 ° C. for 3 days. Next, the reaction solution was desalted using Dowex 50 × 8 (H ⁺ ), and Dowex 1 (HCO
OH) and chromatographic purification with 1.0M-HCOOH aqueous solution,
The title compound was obtained as a colorless syrup (1.8 g, 26
%).

Rf = 0.30 (4: 1: 1 = 2-propanol: acetic acid: water); [α] _D ²⁵ = -19.7 ° (c = 1.2, H ₂ O); MS (FAB) m / e 324 ( M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 1.80 (1H, dd, J =
12.0, 12.0 Hz), 2.00 (3H, s), 2.10 (1H, dd, J =
4.5, 12.0 Hz), 3.48 (3H, s), 3.50-3.80 (7H, m). (Iv) 5-Acetamide-3,5-dideoxy-7-O-
Methyl-D-glycero-D-galact-2-nonulopyra
Methyl nosonate The compound obtained in Example 28 (iii) (680 mg, 2.10 mmol)
l) was dissolved in methanol (20 ml), a cation exchange resin (Dowex 50 × 8 (H ⁺ )) (500 mg) was added, and the mixture was stirred at room temperature for 15 hours. After the reaction, dowex 50x8
(H ⁺ ) was filtered off and the solvent was distilled off. The residue was purified by silica gel chromatography (5: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (340 mg, 48%).

[0366] Rf = 0.15 (5: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 30.2 ° (c = 1.1, CH 3 OH); MS (FAB) m / e 338 (M + + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 1.90 (1H, dd, J
= 12.0, 14.0 Hz), 2.00 (3H, s), 2.16 (1H, dd, J =
4.5, 12.0 Hz), 3.40 (1H, m), 3.45 (3H, s), 3.50-
3.80 (3H, m), 3.77 (3H, s), 3.80-4.00 (2H, m), 4.2
0 (1H, dd, J = 1.5, 9.5 Hz). (V) 5-acetamido-4,8,9-tri-O-acetyl
-2,3,5-trideoxy-7-O-methyl-D-g
Lysero-D-galacto-non-2-enopyranosonic acid
Chill Compound obtained in Example 28 (iv) (686 mg, 2.03 mmol)
Was dissolved in pyridine (10 ml) and acetic anhydride (10 ml),
Stirred at room temperature for 15 hours. The solvent was distilled off and the residue was 4M-
It was dissolved in hydrochloric acid / dioxane solution (20 ml) and stirred at room temperature for 15 hours. The solvent is distilled off, the residue is dissolved in benzene,
There, 1,8-diazabicyclo [5.4.0] -7-undecene (182
mg, 1.20 mmol) and stirred at room temperature for 2 hours. The reaction solution was poured into a two-layer solution of methylene chloride (30 ml) and a saturated aqueous solution of ammonium chloride (15 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (5
Purification with 0: 1 = methylene chloride: methanol) afforded the title compound as a colorless amorphous (310 mg, 34
%).

[0367] Rf = 0.30 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = +206 ° (c = 0.15, CHCl 3); MS (FAB) m / e 446 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 2.00 (3H, s), 2.
06 (3H, s), 2.08 (3H, s), 2.10 (3H, s), 3.50 (3H,
s), 3.65 (1H, dd, J = 3.0, 3.0 Hz), 3.80 (3H, s),
4.20-4.35 (2H, m), 4.45 (1H, m), 4.70 (1H, dd, J =
3.0, 12.0 Hz), 5.35 (1H, m), 5.50 (1H, dd, J = 3.
0, 7.0 Hz), 5.55 (1H, d, J = 8.0 Hz), 6.00 (1H,
(vi) 5-Acetamide-4-azido-8,9-di-O-
Acetyl-2,3,4,5,7-pentadeoxy-7-
Methoxy-D-glycero-D-galacto-non-2-e
Methyl nopyranosonate The compound obtained in Example 28 (v) (303 mg, 0.67 mmol)
Was dissolved in anhydrous methylene chloride (10 ml), and methanol (2
2 mg, 0.67 mmol). Then, under nitrogen atmosphere,
Boron trifluoride ether complex (BF ₃ OEt ₂ ) (956 mg, 6.74 m
mol) and stirred at room temperature for 24 hours. The reaction solution was washed with water (2
0 ml), ice (10 g), solid sodium bicarbonate (5 g)
) And ethyl acetate (AcOEt) (20 ml) and stirred vigorously for 10 minutes. The organic layer was washed with saturated saline (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue (270 mg) was dissolved in N, N-dimethylformamide (10 ml), and a cation exchange resin (Dowex 50x8 (H ⁺ )) (270 mg) and sodium azide (NaN ₃ ) (90 mg, 1.37 mmol).
Stirred for hours. After the reaction, dowex 50x8
(H ⁺ ) was filtered off and the solvent was distilled off. The residue was washed with ethyl acetate (20 ml) and saturated aqueous sodium hydrogen carbonate solution (10 m
The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless syrup (250 mg, 70%).

[0368] Rf = 0.30 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 97.2 ° (c = 0.25, CHCl 3); MS (FAB) m / e 429 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 2.06 (6H, s),
2.10 (3H, s), 3.50 (3H, s), 3.65 (1H, dd, J = 1.
8, 4.0 Hz), 3.80 (3H, s), 4.25 (1H, dd, J = 5.0,
12.0 Hz), 4.45-4.55 (2H, m), 4.75 (1H, dd, J = 3.
2, 12.0 Hz), 5.35 (1H, m), 5.52 (1H, d, J = 8.2 H
z), 5.98 (1H, d, J = 2.7 Hz). (vii) 5-acetamido-4- (N, N'-bis-t-butyl
Oxycarbonylguanidino) -8,9-di-O-ace
Cyl-2,3,4,5,7-pentadeoxy-7-meth
Xy-D-glycero-D-galacto-non-2-enopi
Methyl lanosonate The compound obtained in Example 28 (vi) (180 mg, 0.42 mmol
) Was dissolved in methanol (10 ml) and Lindlar catalyst
(130 mg) and stirred under a hydrogen atmosphere for 2 hours. The catalyst was filtered off and the solvent was distilled off. The residue (120 mg) was dissolved in dimethylformamide (10 ml), and N, N'-di-t-butoxycarbonylthiourea (100 mg, 0.37 mmol), triethylamine (75 mg, 0.74 mmol), mercuric chloride
((HgCl ₂ ) (100 mg, 0.37 mmol) was added and the mixture was stirred for 1 hour at room temperature. The solid was filtered off, and the filtrate was poured into a two-layer solution of ethyl acetate (10 ml) and a saturated aqueous solution of sodium hydrogen carbonate (50 ml). The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel chromatography (2: 1 = hexane: ethyl acetate) to obtain the title compound as a colorless amorphous. (180 mg,
64%).

[0369] Rf = 0.50 (20: 1 = CH 2 Cl 2: MeOH). [Α] D 25 = + 1.85 ° (c = 0.65, CHCl 3); MS (FAB) m / e 645 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.49 (9H, s),
1.50 (9H, s), 1.97 (3H, s), 2.05 (3H, s), 2.07 (3
H, s), 3.52 (3H, s), 3.55 (1H, m), 3.78 (3H, s), 4.
10 (1H, dd, J = 1.0, 10.5 Hz), 4.25-4.40 (2H, m),
4.82 (1H, dd, J = 3.2, 12.0 Hz), 5.12 (1H, ddd, J
= 2.5, 11.0, 11.0 Hz), 5.30 (1H, m), 5.85 (1H, d, J
= 2.3 Hz), 6.35 (1H, d, J = 8.8 Hz), (viii) 5-acetamido-4-guanidino-2,3,
4,5,7-pentadeoxy-7-methoxy-D-gly
Cello-D-galacto-non-2-enopyranosonic acid tri
Fluoroacetate Compound obtained in Example 28 (vii) (53 mg, 0.082 mm
ol) was dissolved in methanol (2 ml), 0.1N sodium methoxide in methanol (0.2 ml) was added, and the mixture was added at room temperature for 1 hour.
Stirred for hours. The reaction solution was neutralized with a hydrochloric acid-containing dioxane solution (4M), and the solvent was distilled off. The residue was dissolved in methylene chloride-trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, the residue was dissolved in distilled water (1 ml), 1N aqueous sodium hydroxide solution (72 ml) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was neutralized with Dowex 50 × 8 (H ⁺ ), and water was distilled off. The residue was chromatographed on silica gel (5: 1: 1 = 2-propanol:
Purification with ethyl acetate: water) gave the title compound as a colorless solid (24 mg, 85%).

Rf = 0.30 (4: 1: 1 = 2-propanol: acetic acid: H ₂ O); [α] _D ²⁵ = -9.3 ° (c = 0.3, CH ₃ OH); MS (FAB) m / e 347 (M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 2.00 (3H, s), 3.37
(3H, s), 3.55 (1H, d, J = 8.5 Hz), 3.65 (1H, dd, J
= 5.0, 12 Hz), 3.80 (1H, dd, J = 2.6, 12Hz), 3.9
0 (1H, m), 4.20 (1H, dd, J = 10, 10 Hz), 4.40-4.50
(2H, m), 5.85 (1H, d, J = 1.8 Hz). (Example 29) 5-Acetamide-4-guanidino-9-O-myristoy
2,3,4,5,7-pentadeoxy-7-methoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 163)
-41) (i) 5-acetamide-4- (N, N'-bis-t-butylo
Xycarbonyl guanidino) -2,3,4,5,7-pe
Ntadeoxy-7-methoxy-D-glycero-D-gal
Diphenylmethyl ct-non-2-enopyranosonate The compound obtained in Example 28 (vii) (87 mg, 0.14 mmol)
l) was dissolved in methanol (5 ml), a 0.4 N sodium methoxide methanol solution (2 ml) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was neutralized with a 4M hydrochloric acid / dioxane solution, and the solvent was distilled off. The residue was dissolved in distilled water (4 ml), and a 1N aqueous sodium hydroxide solution (0.2 ml) was added.
Stirred at room temperature for 1 hour. The reaction solution was neutralized with a 4M hydrochloric acid / dioxane solution, and water was distilled off. Next, the residue was dissolved in a mixture of methanol and dichloromethane (1: 1), and diphenyldiazomethane (47 mg, 0.24 mmol) and boron trifluoride etherate (BF ₃ OEt ₂ ) (50 mg, 0.38 mmol) were added. And stirred at room temperature for 2 hours. After adding acetic acid, the solvent was distilled off, and the residue was subjected to silica gel chromatography (20: 1).
= Methylene chloride: methanol) to give the title compound as a colorless amorphous (29 mg, 30%).

[0371] Rf = 0.3 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 22.0 ° (c = 0.4, CHCl 3); MS (FAB) m / e 713 (M + + H); ¹ H-NMR (CD ₃ OD 270 MHz) δ (ppm): 1.46 (9H, s), 1.52
(9H, s), 1.95 (3H, s), 3.48 (1H, d, J = 9.0 Hz),
3.68 (1H, dd, J = 4.0, 12 Hz), 3.85 (1H, dd, J =
2.5, 12 Hz), 3.95 (1H, m), 4.32 (1H, dd, J = 10,
10 Hz), 4.43 (1H, d, J = 10 Hz), 5.05 (1H, dd, J =
2.2, 10 Hz), 6.02 (1H, d, J = 2.2 Hz), 6.90 (1H,
s), 7.20-7.50 (10H, m). (ii) 5-acetamido-4- (N, N'-bis-t-butylthio)
Xycarbonylguanidino ) -9-O-myristoyl-
2,3,4,5,7-pentadeoxy-7-methoxy-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 29 (i) (28 mg, 0.039 mmo
l) in methylene chloride (2 ml), triethylamine (6 mg, 0.06 mmol) and myristoyl chloride (8 mg,
(0.05 mmol) was added under ice-cooling, and the mixture was stirred at 0 ° C for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (50: 1).
= Methylene chloride: methanol) to give the title compound as a colorless amorphous (22 mg, 61%).

[0372] Rf = 0.45 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 40.5 ° (c = 0.2, CHCl 3); MS (FAB) m / e 923 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20-1.30 (20H, m), 1.48 (9H, s), 1.50 (9H, s), 1.55
-1.70 (2H, m), 1.98 (3H, s), 2.33 (2H, t, J = 7.5 H
z), 3.40 (1H, m), 3.48 (3H, s), 4.10-4.50 (5H,
m), 5.18 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.18 (1H, d, J = 8.7 Hz), 6.92
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Iii) 5-acetamido-4-guanidino-9-O-milli.
Styl-2,3,4,5,7-pentadeoxy-7-
Methoxy-D-glycero-D-galacto-non-2-e
Nopyranosonic acid trifluoroacetate Compound obtained in Example 29 (ii) (22 mg, 0.024 mmo
l) in methylene chloride-trifluoroacetic acid (3: 1) (3 m
l) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (10 mg, 74%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 24.0 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 557 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.25-1.40 (20H, m), 1.60-1.70 (2H, m), 2.00 (3H,
s), 2.37 (2H, t, J = 7.5 Hz), 3.38 (3H, s), 3.45 (1
H, m), 4.10-4.40 (6H, m), 5.53 (1H, d, J = 1.8 H
z). (Example 30) 5-Acetamide-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-ethoxy-D-glycero-D-
Galacto-non-2-enoic acid trifluoroacetate
( Exemplified Compound No. 199-1) (i) Benzyl N-acetyl-3,6-di-O-benzyl
4-O-ethyl-α-D-glucosamine Carbohydrate Res. 83 , 163-1
69 (1980). Benzyl N-acetyl-3,6-di-O-benzyl-α
-D-Glucosamine (8.35 g, 16.8 mmol) was dissolved in dimethylformamide (80 ml) and sodium hydride (1.84 g) was dissolved.
g, 42.2 mmol) and stirred at room temperature for 30 minutes. Then, ethyl iodide (2.86 g, 18.5 mmol) was added at 0 ° C., and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction solution was poured into a two-layer solution of ethyl acetate (200 ml) and a saturated aqueous solution of sodium hydrogencarbonate (100 ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was removed. Distilled off. The residue was purified by silica gel chromatography (4: 1 = methylene chloride: ethyl acetate) to give the title compound as a colorless solid (7.0 g, 80%).

[0374] Rf = 0.55 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} +123 ° (c = 2.3, CHCl 3); MS (FAB) m / e 520 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.10 (3H, t, J
= 7.0 Hz), 1.80 (3H, s), 3.40-3.90 (7H, m), 4.21
(1H, ddd, J = 3.5, 10.0, 10.0 Hz), 4.40-4.90 (7
H, m), 5.22 (1H, d, J = 10.0 Hz), 7.20-7.40 (15H,
m). (ii) N-acetyl-4-O-ethyl-α-D-glucosa
The compound obtained in Example 30 (i) (7.0 g, 13.4 mmol)
) In acetic acid (60 ml) and palladium on carbon (10 g)
) Was added and the mixture was stirred under a hydrogen atmosphere of 3 atm for 30 hours. After completion of the reaction, the catalyst was filtered off, the solvent was distilled off, and the obtained residue was purified by silica gel chromatography (10: 1-5: 1 = methylene chloride: methanol) to obtain the title compound as a colorless solid. (2.4 g, 81%).

[0375] Rf = 0.35 (5: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 66.1 ° (c = 2.1, CH 3 OH); MS (FAB) m / e 250 (M + + H) ; ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 1.15 (3H, t, J =
7.0 Hz), 2.00 (3H, s), 3.33 (2H, q, J = 7.0 Hz),
3.60-3.90 (6H, m), 5.15 (1H, s). (Iii) 5-acetamido-3,5-dideoxy-7-O-
Ethyl-D-glycero-D-galact-2-nonulopyra
Nosonic acid The compound obtained in Example 30 (ii) (5.0 g, 20.1 mmol)
Was dissolved in distilled water, and sodium azide (100 mg) and sodium pyruvate (5.0 g, 45.5 mmol) were added.
The pH of the reaction solution was adjusted to 10 using an aqueous solution of sodium hydroxide.
To 11. Then, 25 mg (660 U) of N-acetyl-neuraminic acid aldolase (TOYOBO) was added, and 20
Stirred at C for 3 days. After completion of the reaction, the reaction solution was desalted using Dowex 50 × 8 (H ⁺ ), and Dowex 1 (H
(COOH) and chromatographed with 1.0M-HCOOH aqueous solution to give the title compound as a colorless syrup (500 mg, 7.4
%).

Rf = 0.20 (4: 1: 1 = 2-propanol: acetic acid: water); [α] ₂₅ ^D = −8.4 ° (c = 0.19, CH ₃ OH); MS (FAB) m / e 338 ( M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 1.05 (3H, t, J =
7.0), 1.80 (1H, dd, J = 12.0, 12.0 Hz), 2.00 (3H,
s), 2.20 (1H, dd, J = 4.5, 12.0 Hz), 3.50-3.80 (7
H, m). (Iv) 5-acetamido-3,5-dideoxy-7-O-
Ethyl-D-glycero-D-galact-2-nonulopyra
Methyl nosonate The compound obtained in Example 30 (iii) (1.9 g, 5.64 mmol)
l) was dissolved in methanol (60 ml), a cation exchange resin (Dowex 50 × 8 (H ⁺ )) (600 mg) was added, and the mixture was stirred at room temperature for 15 hours. After the reaction, dowex 50x8
(H ⁺ ) was filtered off and the solvent was distilled off. The residue was purified by silica gel chromatography (5: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (1.4 g, 71%).

[0377] Rf = 0.3 (5: 1 = CH 2 Cl 2: MeOH); [α] D 25 = -7.5 ° (c = 0.10, CHCl 3); MS (FAB) m / e 352 (M + + H ); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 1.17 (3H, t, J
= 7.0), 1.95 (1H, dd, J = 12.0, 14.0 Hz), 2.00 (3H,
s), 2.16 (1H, dd, J = 4.5, 12.0 Hz), 3.42 (1H, dd,
J = 1.5, 8.0 Hz), 3.60 (2H, q, J = 7.0 Hz), 3.77
(3H, s), 3.70-4.00 (4H, m), 4.15 (1H, dd, J = 1.5,
(V) 5-acetamide-4,8,9-tri-O-acetyl
-2,3,5,7-tetradeoxy-7-ethoxy-D
-Glycero-D-galacto-non-2-enopyranosone
The compound obtained in methyl Example 30 (iv) (1.4 g, 3.99 mmol)
Was dissolved in pyridine (20 ml) and acetic anhydride (10 ml) and stirred at room temperature for 15 hours. The solvent was distilled off, the residue was dissolved in a 4 M hydrochloric acid / dioxane solution (50 ml), and the mixture was stirred at room temperature for 15 hours. The solvent was distilled off, and the residue was dissolved in benzene.
8-diazabicyclo [5.4.0] -7-undecene (952 mg, 6.30
mmol) and stirred at room temperature for 2 hours. The reaction mixture was diluted with methylene chloride (30 ml) and a saturated aqueous ammonium chloride solution (15 ml).
ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off.
The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (1.1 g, 60%).

[0378] Rf = 0.30 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 24.1 ° (c = 0.5, CHCl 3); MS (FAB) m / e 460 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.20 (3H, t, J
= 7.0), 1.98 (3H, s), 2.05 (3H, s), 2.08 (3H, s),
3.50-3.80 (3H, m), 3.80 (3H, s), 4.20-4.35 (2H, m),
4.45 (1H, m), 4.70 (1H, dd, J = 3.2, 12.0 Hz), 5.
33 (1H, m), 5.47 (1H, dd, J = 3.3, 7.0 Hz), 5.51
(1H, d, J = 7.0 Hz), 6.00 (1H, d, J = 3.3 Hz). (Vi) 5-Acetamide-4-azido-8,9-di-O-
Acetyl-2,3,4,5,7-pentadeoxy-7-
Ethoxy-D-glycero-D-galacto-non-2-e
Methyl nopyranosonate The compound obtained in Example 30 (v) (1000 mg, 2.18 mmol
) In anhydrous methylene chloride (20 ml)
(25 mg, 0.78 mmol) was added. Then, under a nitrogen atmosphere, boron trifluoride ether complex (BF ₃ OEt ₂ ) (3.1 g, 21.
8 mmol) and stirred at room temperature for 24 hours. The reaction solution was poured into a mixed solution of water (50 ml), ice (10 g), solid sodium hydrogen carbonate (10 g) and ethyl acetate (AcOEt) (50 ml), and stirred vigorously for 10 minutes. The organic layer was washed with saturated saline (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue (800 mg) was dissolved in N, N-dimethylformamide (10 ml), and a cation exchange resin (Dowex 50 × 8 (H ⁺ )) (800 mg) and sodium azide (NaN ₃ ) (400 mg, 6.15 mmol) and 90 ° C
Stir for 4 hours. After the reaction, dowex 50x8
(H ⁺ ) was filtered off and the solvent was distilled off. The residue was treated with ethyl acetate (30 ml) and a saturated aqueous sodium hydrogen carbonate solution (20 ml).
The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless syrup (600 mg, 63%).

[0379] Rf = 0.30 (20: 1 = CH 2 Cl 2: MeOH); [α] D 25 = + 72.6 ° (c = 0.05, CHCl 3); MS (FAB) m / e 443 (M + + H ); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.25 (3H, t, J =
7.0), 2.09 (3H, s), 2.10 (3H, s), 2.13 (3H, s), 3.5
0-3.80 (3H, m), 3.80 (3H, s), 4.05 (1H, m), 4.25
(1H, dd, J = 5.0, 12.0 Hz), 4.45-4.55 (2H, m), 4.8
0 (1H, dd, J = 3.2, 12.0 Hz), 5.35 (1H, m), 5.51
(1H, d, J = 8.2 Hz), 6.00 (1H, d, J = 2.7 Hz). (Vii) 5-acetamide-4- (N, N'-bis-t-butyl
Oxycarbonylguanidino) -8,9-di-O-ace
Cyl-2,3,4,5,7-pentadeoxy-7-eth
Xy-D-glycero-D-galacto-non-2-enopi
Methyl lanosonate The compound obtained in Example 30 (vi) (580 mg, 1.31 mmol
) Was dissolved in methanol (10 ml) and Lindlar catalyst
(270 mg), and the mixture was stirred under a hydrogen atmosphere for 2 hours. The catalyst was filtered off and the solvent was distilled off. The residue (400 mg) was dissolved in N, N-dimethylformamide (10 ml) and N, N-di-t
-Butoxycarbonylthiourea (408 mg, 1.48 mmol
l), triethylamine (300 mg, 2.95 mmol) and mercuric chloride ((HgCl ₂ ) (402 mg, 1.48 mmol) were added, and the mixture was stirred at room temperature for 1 hour. 20 ml) and a saturated aqueous solution of sodium hydrogen carbonate (10 ml), and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. 1 = hexane: ethyl acetate) to give the title compound as a colorless amorphous (530 mg, 61%) Rf = 0.40 (20: 1 = CH 2 Cl 2:. MeOH); [α] D 25 = +2.8 ° (c = 0.05, CHCl ₃ ); MS (FAB) m / e 659 (M ⁺ + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.20 (3H, t, J =
7.0), 1.49 (9H, s), 1.50 (9H, s), 1.95 (3H, s), 2.0
6 (3H, s), 2.09 (3H, s), 3.50-3.80 (3H, m), 3.80
(3H, s), 4.10 (1H, dd, J = 1.0, 10.5 Hz), 4.25-4.
40 (2H, m), 4.80 (1H, dd, J = 3.2, 12.0 Hz), 5.10
(1H, ddd, J = 2.5, 11.0, 11.0 Hz), 5.30 (1H, m),
5.83 (1H, d, J = 2.3 Hz), 6.20 (1H, d, J = 8.8 H
z), (viii) 5-acetamido-4-guanidino-2,3,4,
5,7-pentadeoxy-7-ethoxy-D-glycero
-D-galacto-non-2-enopyranosonic acid trifur
The compound obtained in Oro acetate Example 30 (vii) (50 mg, 0.076 mm
ol) was dissolved in methanol (2 ml), 0.1N sodium methoxide / methanol solution (0.2 ml) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was neutralized with a 4M hydrochloric acid / dioxane solution, and the solvent was distilled off. The residue was dissolved in a mixture of methylene chloride and trifluoroacetic acid (3: 1) (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was distilled water (1
1N sodium hydroxide aqueous solution (110 ml)
Was added and stirred at room temperature for 1 hour. Dowex 50x8
The reaction solution was neutralized with (H ⁺ ), and water was distilled off. The residue was purified by silica gel chromatography (5: 1: 1 = 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (27 mg, 75%).

Rf = 0.30 (4: 1: 1 = 2-propanol: acetic acid: water); [α] _D ²⁵ = + 32.5 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 361 ( M ⁺ + H); ¹ H-NMR (D ₂ O, 270 MHz) δ (ppm): 1.05 (3H, t, J =
7.0), 1.97 (3H, s), 3.40 (1H, m), 3.50-3.65 (3H,
m), 3.80 (1H, dd, J = 5.0, 12 Hz), 3.90 (1H, m),
4.15 (1H, dd, J = 10, 10 Hz), 4.40-4.50 (2H, m), 5.5
5 (1H, d, J = 1.8 Hz). (Example 31) 5-Acetamide-4-guanidino-9-O-octanoy
2,3,4,5,7-pentadeoxy-7-ethoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 199)
-38) (i) 5-Acetamide-4- (N, N'-bis-t-butylo
Xycarbonyl guanidino) -2,3,4,5,7-pe
Ntadeoxy-7-ethoxy-D-glycero-D-gal
Diphenylmethyl ct-non-2-enopyranosonate The compound obtained in Example 30 (vii) (495 mg, 0.75 mmol)
l) was dissolved in methanol (10 ml), 0.1N sodium methoxide / methanol solution (2 ml) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was neutralized with a 4 M hydrochloric acid / dioxane solution, and the solvent was distilled off. The residue was dissolved in distilled water (10 ml), 1N aqueous sodium hydroxide solution (1.0 ml) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was neutralized with a 4M hydrochloric acid / dioxane solution, and water was distilled off. The obtained residue was dissolved in a mixture of methanol and dichloromethane (6: 1), and diphenyldiazomethane (500 mg, 2.60 mmol), boron trifluoride etherate (BF ₃ OEt ₂ ) (50 mg, 0.38 mmol)
l) was added and the mixture was stirred at room temperature for 2 hours. After adding acetic acid,
The solvent was distilled off, and the residue was purified by silica gel chromatography (20: 1 = methylene chloride: methanol) to obtain the title compound as a colorless amorphous (450 mg, 82 mg).
%).

[0381] Rf = 0.25 (10: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -10.7 ° (c = 0.13, CHCl 3); MS (FAB) m / e 727 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 1.20 (3H, t, J =
7.0 Hz), 1.48 (9H, s), 1.50 (9H, s), 1.95 (3H,
s), 3.60-4.10 (6H, m), 4.30-4.50 (2H, m), 5.10 (1
H, m), 5.95 (1H, d, J = 2.7 Hz), 6.55 (1H, d, J =
8.0 Hz), 6.95 (1H, s), 7.20-7.50 (10H, m), 8.50 (1
(Ii) 5-acetamide-4- (N, N'-bis-t-butylthio ).
(Xycarbonylguanidino) -9-O-octanoyl-
2,3,4,5,7-pentadeoxy-7-ethoxy-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 31 (i) (30 mg, 0.041 mmo
l) was dissolved in methylene chloride (2 ml), and triethylamine (6 mg, 0.06 mmol), octanoyl chloride (8 mg, 0.
(05 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was treated with ethyl acetate (5 ml) and saturated aqueous sodium hydrogen carbonate solution (3
ml), and the organic layer was washed with saturated saline, dried over sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (24 mg, 69%).

[0382] Rf = 0.30 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -14.0 ° (c = 0.05, CHCl 3); MS (FAB) m / e 854 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m),
1.20 (3H, t, J = 7.0Hz), 1.20-1.30 (8H, m), 1.48
(9H, s), 1.50 (9H, s), 1.55-1.70 (2H, m), 1.95 (3H,
s), 2.33 (2H, t, J = 7.5 Hz), 3.50 (1H, t, J = 5.
5 Hz), 3.59 (2H, q, J = 7.0 Hz), 4.10-4.50 (5H,
m), 5.10 (1H, ddd, J = 2.4, 9.0, 9.0Hz), 5.95 (1H,
d, J = 2.3 Hz), 6.10 (1H, d, J = 8.7 Hz), 6.94 (1
H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7 H
z). (iii) 5-acetamido-4-guanidino-9-O-oct
Tanoyl-2,3,4,5,7-pentadeoxy-7-
Ethoxy-D-glycero-D-galacto-non-2-e
Nopyranosonic acid trifluoroacetate Compound obtained in Example 31 (ii) (20 mg, 0.023 mmo
l) as a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (10 mg, 73
%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 55 ° (c 0.10, CH ₃ OH); MS (FAB) m / e 487 ( M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m), 1.
15 (3H, t, J = 7.0 Hz), 1.20-1.40 (8H, m), 1.55-1.
70 (2H, m), 2.00 (3H, s), 2.35 (2H, t, J = 7.5 Hz),
3.45-3.60 (3H, m), 4.10-4.40 (6H, m), 5.53 (1H, d,
(J = 1.8 Hz). (Example 32) 5-Acetamide-4-guanidino-9-O-dodecanoy
2,3,4,5,7-pentadeoxy-7-ethoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 199)
-40) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
(Xycarbonylguanidino) -9-O-dodecanoyl-
2,3,4,5-pentadeoxy-7-ethoxy-D-
Glycero-D-galacto-non-2-enopyranosonic acid
Diphenylmethyl Compound obtained in Example 31 (i) (30 mg, 0.041 mmo
l) was dissolved in methylene chloride (2 ml), and triethylamine (6 mg, 0.06 mmol) and dodecanoyl chloride (11 mg) were dissolved.
, 0.05 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour.
The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (5
Purification with 0: 1 methylene chloride: methanol) afforded the title compound as a colorless amorphous (29 mg, 78).
%).

[0384] Rf = 0.35 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -9.0 ° (c = 0.1, CHCl 3); MS (FAB) m / e 910 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20 (3H, t, J = 7.0 Hz), 1.20-1.30 (16H, m), 1.48
(9H, s), 1.50 (9H, s), 1.55-1.70 (2H, m), 1.95 (3
H, s), 2.33 (2H, t, J = 7.5 Hz), 3.50 (1H, t, J =
5.5 Hz), 3.59 (2H, q, J = 7.0 Hz), 4.10-4.50 (5H,
m), 5.10 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.10 (1H, d, J = 8.7 Hz), 6.94
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-dodeca
Noyl-2,3,4,5,7-pentadeoxy-7-e
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 14 (i) (28 mg, 0.03 mmol)
With methylene chloride and trifluoroacetic acid (3: 1) (3 m
l) and stirred at room temperature for 5 hours. Evaporate the solvent,
The residue was subjected to silica gel chromatography (2: 5: 1 = 2
-Propanol: ethyl acetate: water) to give the title compound as a colorless solid (12 mg, 61%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [[α] _D ²⁵ = + 50 ° (c = 0.05, CH ₃ OH); MS (FAB) m / e 543 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.15 (3H, t, J = 7.0 Hz), 1.20-1.40 (16H, m), 1.55
-1.70 (2H, m), 2.00 (3H, s), 2.35 (2H, t, J = 7.5 H
z), 3.45-3.60 (3H, m), 4.10-4.40 (6H, m), 5.53 (1
(H, d, J = 1.8 Hz). (Example 33) 5-Acetamide-4-guanidino-9-O-myristoy
2,3,4,5,7-pentadeoxy-7-ethoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (199-41) (i) 5-acetamido-4- (N, N'-bis-t-butylo
(Xycarbonylguanidino) -9-O-myristoyl-
2,3,4,5,7-pentadeoxy-7-ethoxy-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 31 (i) (30 mg, 0.041 mmo
l) was dissolved in methylene chloride (2 ml), and triethylamine (6 mg, 0.06 mmol), myristoyl chloride (12 mg,
(0.05 mmol) was added under ice-cooling, and the mixture was stirred at 0 ° C for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (50: 1).
= Methylene chloride: methanol) to give the title compound as a colorless amorphous (30 mg, 78%).

[0386] Rf = 0.35 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -8.0 ° (c = 0.1, CHCl 3); MS (FAB) m / e 938 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20 (3H, t, J = 7.0 Hz), 1.20-1.30 (20H, m), 1.48
(9H, s), 1.50 (9H, s), 1.55-1.70 (2H, m), 1.95 (3
H, s), 2.33 (2H, t, J = 7.5 Hz), 3.50 (1H, t, J =
5.5 Hz), 3.59 (2H, q, J = 7.0 Hz), 4.10-4.50 (5H,
m), 5.10 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.10 (1H, d, J = 8.7 Hz), 6.94
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-myris
Toyl-2,3,4,5,7-pentadeoxy-7-e
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 33 (i) (28 mg, 0.03 mmol)
Is a mixture of methylene chloride and trifluoroacetic acid (3: 1)
(3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2: 5: 1).
= 2-propanol: ethyl acetate: water) to give the title compound as a colorless solid (13 mg, 74%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 38.0 ° (c = 0.05, CH ₃ OH); MS (FAB) m / e 571 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.15 (3H, t, J = 7.0 Hz), 1.20-1.40 (20H, m), 1.55
-1.70 (2H, m), 2.00 (3H, s), 2.35 (2H, t, J = 7.5 H
z), 3.45-3.60 (3H, m), 4.10-4.40 (6H, m), 5.53 (1
(H, d, J = 1.8 Hz). (Example 34) 5-Acetamide-4-guanidino-9-O-palmitoy
2,3,4,5,7-pentadeoxy-7-ethoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 199)
-42) (i) 5-acetamido-4- (N, N'-bis-t-butylo
(Xycarbonylguanidino) -9-O-palmitoyl-
2,3,4,5,7-pentadeoxy-7-ethoxy-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 31 (i) (30 mg, 0.041 mmo
l) was dissolved in methylene chloride (2 ml), triethylamine (6 mg, 0.06 mmol), palmitoyl chloride (14 mg,
(0.05 mmol) was added under ice-cooling, and the mixture was stirred at 0 ° C for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (50: 1).
= Methylene chloride: methanol) to give the title compound as a colorless amorphous (31 mg, 78%).

[0388] Rf = 0.35 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} -7.5 ° (c = 0.1, CHCl 3); MS (FAB) m / e 966 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.2
0 (3H, t, J = 7.0 Hz), 1.20-1.30 (24H, m), 1.48 (9
H, s), 1.50 (9H, s), 1.55-1.70 (2H, m), 1.95 (3H,
s), 2.33 (2H, t, J = 7.5 Hz), 3.50 (1H, t, J = 5.5
Hz), 3.59 (2H, q, J = 7.0 Hz), 4.10-4.50 (5H,
m), 5.10 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.10 (1H, d, J = 8.7 Hz), 6.94
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-palmi
Toyl-2,3,4,5,7-pentadeoxy-7-e
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 34 (i) (28 mg, 0.029 mmo
l) as a mixture of methylene chloride and trifluoroacetic acid (3:
1) Dissolved in (3 ml) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was subjected to silica gel chromatography (2:
Purification with 5: 1 = 2-propanol: ethyl acetate: water) gave the title compound as a colorless solid (12 mg, 58).
%).

Rf = 0.3 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 30.0 ° (c = 0.1, CH ₃ OH); MS (FAB) m / e 599 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.15 (3H, t, J = 7.0 Hz), 1.20-1.40 (24H, m), 1.55
-1.70 (2H, m), 2.00 (3H, s), 2.35 (2H, t, J = 7.5 H
z), 3.45-3.60 (3H, m), 4.10-4.40 (6H, m), 5.53 (1
(H, d, J = 1.8 Hz). (Example 35) 5-Acetamide-4-guanidino-9-O-octanoy
2,3,4,5,7-pentadeoxy-7-methoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 163)
-38) (i) 5-acetamido-4- (N, N'-bis-t-butylo)
(Xycarbonylguanidino) -9-O-octanoyl-
2,3,4,5,7-pentadeoxy-7-methoxy-
D-glycero-D-galacto-non-2-enopyranoso
Diphenylmethyl phosphate Compound obtained in Example 29 (i) (57 mg, 0.08 mmol)
Was dissolved in methylene chloride (2 ml) and triethylamine (11 mg, 0.10 mmol) and octanoyl chloride (16 m
g, 0.09 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour.
The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (5
Purification with 0: 1 methylene chloride: methanol) afforded the title compound as a colorless amorphous (38 mg, 58
%).

[0390] Rf = 0.5 (10: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 2.7 ° (c = 0.11, CHCl 3); MS (FAB) m / e 839 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20-1.30 (8H, m), 1.48 (9H, s), 1.50 (9H, s), 1.55-
1.70 (2H, m), 1.98 (3H, s), 2.33 (2H, t, J = 7.5 H
z), 3.40 (1H, m), 3.48 (3H, s), 4.10-4.50 (5H,
m), 5.18 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.18 (1H, d, J = 8.7 Hz), 6.92
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-octa.
Noyl-2,3,4,5,7-pentadeoxy-7-me
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 35 (i) (31 mg, 0.037 mmo
l) in methylene chloride-trifluoroacetic acid (3: 1) (3 m
l) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (10 mg, 74%).

Rf = 0.34 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 38.2 ° (c = 0.11, CH ₃ OH); MS (FAB) m / e 473 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.25-1.40 (8H, m), 1.60-1.70 (2H, m), 2.00 (3H,
s), 2.37 (2H, t, J = 7.5 Hz), 3.38 (3H, s), 3.45 (1
H, m), 4.10-4.40 (6H, m), 5.53 (1H, d, J = 1.8 H
z). (Example 36) 5-Acetamide-4-guanidino-9-O-decanoyl
-2,3,4,5,7-pentadeoxy-7-methoxy
-D-glycero-D-galacto-non-2-enopyrano
Sonic acid trifluoroacetate (Exemplified Compound No. 163-
39) (i) 5-acetamido-4- (N, N'-bis-t-butylo)
(Xycarbonylguanidino) -9-O-decanoyl-
2,3,4,5,7-pentadeoxy-7-methoxy-
D-glycero-D-galacto-non-2-enopyranoso
Diphenylmethyl phosphate Compound obtained in Example 29 (i) (56 mg, 0.08 mmol)
) Was dissolved in methylene chloride (2 ml), and triethylamine (11 mg, 0.10 mmol) and decanoyl chloride (18 mg) were dissolved.
, 0.09 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour.
The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (5
Purification with 0: 1 methylene chloride: methanol) afforded the title compound as a colorless amorphous (40 mg, 50 mg).
%).

[0392] Rf = 0.45 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 13.9 ° (c = 0.11, CHCl 3); MS (FAB) m / e 867 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20-1.30 (12H, m), 1.48 (9H, s), 1.50 (9H, s), 1.55
-1.70 (2H, m), 1.98 (3H, s), 2.33 (2H, t, J = 7.5 H
z), 3.40 (1H, m), 3.48 (3H, s), 4.10-4.50 (5H,
m), 5.18 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.18 (1H, d, J = 8.7 Hz), 6.92
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-decano
Yl-2,3,4,5,7-pentadeoxy-7-meth
Xy-D-glycero-D-galacto-non-2-enopi
Lanosonic acid trifluoroacetate Compound obtained in Example 36 (i) (33 mg, 0.04 mmol)
To methylene chloride-trifluoroacetic acid (3: 1) (3 ml)
And stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (20 mg, 85%).

Rf = 0.34 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 33.3 ° (c = 0.11, CH ₃ OH); MS (FAB) m / e 501 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.25-1.40 (12H, m), 1.60-1.70 (2H, m), 2.00 (3H,
s), 2.37 (2H, t, J = 7.5 Hz), 3.38 (3H, s), 3.45 (1
H, m), 4.10-4.40 (6H, m), 5.53 (1H, d, J = 1.8 H
z). (Example 37) 5-Acetamide-4-guanidino-9-O-dodecanoy
2,3,4,5,7-pentadeoxy-7-methoxy
S-D-glycero-D-galacto-non-2-enopyra
Nosonic acid trifluoroacetate (Exemplary Compound No. 163)
-40) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
(Xycarbonylguanidino) -9-O-dodecanoyl-
2,3,4,5,7-pentadeoxy-7-methoxy-
D-glycero-D-galacto-non-2-enopyranoso
The compound obtained in phosphate diphenylmethyl Example 29 (i) (51 mg, 0.07 mmol
) Was dissolved in methylene chloride (2 ml) and triethylamine (9 mg, 0.09 mmol) and dodecanoyl chloride (19 mg,
0.09 mmol) was added under ice-cooling, and the mixture was stirred at 0 ° C for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was chromatographed on silica gel (50: 1).
= Methylene chloride: methanol) to give the title compound as a colorless amorphous (39 mg, 61%).

[0394] Rf = 0.6 (20: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} + 2.5 ° (c = 0.13, CHCl 3); MS (FAB) m / e 895 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20-1.30 (16H, m), 1.48 (9H, s), 1.50 (9H, s), 1.55
-1.70 (2H, m), 1.98 (3H, s), 2.33 (2H, t, J = 7.5 H
z), 3.40 (1H, m), 3.48 (3H, s), 4.10-4.50 (5H,
m), 5.18 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.18 (1H, d, J = 8.7 Hz), 6.92
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-dodeca
Noyl-2,3,4,5,7-pentadeoxy-7-me
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 37 (i) (31 mg, 0.035 mmo
l) in methylene chloride-trifluoroacetic acid (3: 1) (3 m
l) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (22 mg, 98%).

Rf = 0.4 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 25.8 ° (c = 0.16, CH ₃ OH); MS (FAB) m / e 529 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.25-1.40 (16H, m), 1.60-1.70 (2H, m), 2.00 (3H,
s), 2.37 (2H, t, J = 7.5 Hz), 3.38 (3H, s), 3.45 (1
H, m), 4.10-4.40 (6H, m), 5.53 (1H, d, J = 1.8 H
z). (Example 38) 5-Acetamide-4-guanidino-9-O-hexadeca
Noyl-2,3,4,5,7-pentadeoxy-7-me
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate (Exemplary Compound No. 1
63-42) (i) 5-acetamido-4- (N, N'-bis-t-butylthio)
Xycarbonyl guanidino) -9-O-hexadecanoi
2,3,4,5,7-pentadeoxy-7-methoxy
S-D-glycero-D-galacto-non-2-enopyra
Diphenylmethyl nosonate The compound obtained in Example 29 (i) (50 mg, 0.07 mmol)
) Was dissolved in methylene chloride (2 ml) and triethylamine (9 mg, 0.09 mmol) and hexadecanoyl chloride (23
mg, 0.084 mmol) under ice-cooling and stirred at 0 ° C. for 1 hour. The reaction solution was poured into a two-layer solution of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogen carbonate (3 ml), and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (50: 1 = methylene chloride: methanol) to give the title compound as a colorless amorphous (40 mg, 60 mg).
%).

[0396] Rf = 0.6 (10: 1 = methylene chloride: ^{_{methanol); [α] D 25 =}} +5.5 ° (c = 0.11, CHCl 3); MS (FAB) m / e 951 (M + + H); ¹ H-NMR (CDCl ₃ , 270 MHz) δ (ppm): 0.85 (3H, m), 1.
20-1.30 (24H, m), 1.48 (9H, s), 1.50 (9H, s), 1.55
-1.70 (2H, m), 1.98 (3H, s), 2.33 (2H, t, J = 7.5 H
z), 3.40 (1H, m), 3.48 (3H, s), 4.10-4.50 (5H,
m), 5.18 (1H, ddd, J = 2.4, 9.0, 9.0 Hz), 5.95 (1
H, d, J = 2.3 Hz), 6.18 (1H, d, J = 8.7 Hz), 6.92
(1H, s), 7.20-7.50 (10H, m), 8.55 (1H, d, J = 8.7
(Ii) 5-acetamido-4-guanidino-9-O-hexa ).
Decanoyl-2,3,4,5-tetradeoxy-7-me
Toxi-D-glycero-D-galacto-non-2-eno
Pyranosonic acid trifluoroacetate Compound obtained in Example 38 (i) (34 mg, 0.036 mmo
l) in methylene chloride-trifluoroacetic acid (3: 1) (3 m
l) and stirred at room temperature for 5 hours. The solvent was distilled off, and the residue was purified by silica gel chromatography (2: 5: 1 = 2-propanol: ethyl acetate: water) to obtain the title compound as a colorless solid (23 mg, 92%).

Rf = 0.47 (2: 5: 1 = 2-propanol: ethyl acetate: water); [α] _D ²⁵ = + 21.6 ° (c = 0.12, CH ₃ OH); MS (FAB) m / e 585 (M ⁺ + H); ¹ H-NMR (CD ₃ OD, 270 MHz) δ (ppm): 0.90 (3H, m),
1.25-1.40 (24H, m), 1.60-1.70 (2H, m), 2.00 (3H,
s), 2.37 (2H, t, J = 7.5 Hz), 3.38 (3H, s), 3.45 (1
H, m), 4.10-4.40 (6H, m), 5.53 (1H, d, J = 1.8 H
(Test Example 1) Influenza virus replication inhibitory activity Influenza virus A prepared by growing in embryonated chicken eggs
By comparing the number of plaques produced when the / Yamagata / 32/89 (H1N1) strain was infected and propagated in MDCK cells (canine kidney-derived cells) in the presence and absence of the compound of the present invention, The influenza virus replication inhibitory activity was calculated.

[0398] In this test, Antimicrobial Agents a
nd Chemotherapy, Vol. 17, 865-870 (1980).

That is, at 37 ° C. in 5% carbon dioxide,
MDCK cells were cultured on a single layer in a 5 mm Petri dish.
The culture was decanted off and instead a virus-buffered saline of virus prepared in advance to form 50-100 plaques was added.

After leaving the virus adsorbed at 37 ° C. for 1 hour to adsorb the virus, the virus solution was decanted and replaced with a final concentration of 1 μg / ml trypsin (Coop).
Biomedical), 0.01% DEAE dextran (Pharmacia LKB), 0.6% agar (Sigma)
MEM medium (Gibco BRL) containing the compound of the present invention at a concentration of 0.0005 to 5.6 μg / ml was added to solidify the cells.

After culturing was continued in 5% carbon dioxide at 37 ° C. for 40 hours, the solidified agar medium was removed, and a final concentration of 0.01% crystal violet (Merck) dissolved in 19% methanol was added. After fixing and staining, the number of plaques was measured.

When the number of plaques generated in the absence of the compound of the present invention is 100%, the number of plaques is 50%.
The concentration of the compound of the present invention, which was reduced to the above, was calculated as IC ₅₀ (nM), which was defined as the influenza virus replication inhibitory activity.

The compounds of the present invention exhibited high influenza virus replication inhibitory activity.

(Results)

[0405]

[Table 3]

[0406]

[Table 4] The compounds A in Tables 3 and 4 described above and Tables 5 and 6 described below are those described in Example 3 in JP-T-5-507068, and the structure is as follows. is there.

[0407]

Embedded image

(Test Example 2) Influenza virus sialidase inhibitory activity Influenza virus A prepared by propagation in embryonated chicken eggs
/ PR / 8/34 (H1N1) was dissolved with a detergent, and the virus membrane fraction was purified by centrifugation and used as a crude influenza virus sialidase. The substrate was p-nitrophenyl N-acetylneuraminic acid ( Analytical Biochemistry, 94
Vol., 287-296 (1979).

The final enzyme activity was about 0.0011 u
Enzyme solutions prepared to give nits / ml (1 unit is the amount of enzyme that hydrolyzes 1 μmole of substrate in 1 minute), aqueous solutions of the compound of the present invention at various concentrations, and a concentration of 33 μm
g / ml substrate aqueous solution and 20 mM 2- (N-morpholino) ethanesulfonic acid buffer (pH 6.5) containing 50 mM calcium chloride were mixed to a final volume of 150 μl, and left at 37 ° C. for 20 minutes. P- formed in solution
Nitrophenol was measured for absorbance at 415 nm. The absorbance at 415 nm measured when water was added instead of the compound aqueous solution of the present invention was taken as 100%, and the sample concentration at which the absorbance was reduced to 50% was calculated as IC ₅₀ (nM), which was used as the influenza virus sialidase inhibitory activity. And (result)

[0410]

[Table 5] IC ₅₀ (nM) {Compound A 9.0 Compound of Example 28 13 Compound of Example 30 7.0} (Test Example 3) Mouse infection experiment 50 μl phosphate buffer containing 0.42% bovine serum albumin
Mouse-adapted influenza virus A / PR / 8 /
A solution containing 34 strains and 1500 pfu (plaque forming unit) was prepared, and mice (BALB / C, female, 5-6 weeks old, 20 g) were intranasally instilled and infected. The compound of the present invention was suspended in physiological saline, and 0.9 μmol / kg / 50 μ
The dose was adjusted so as to be 1 l, and the solution was intranasally instilled 4 times before, 4 hours and 17 hours after the virus infection in total, three times. The results were shown by the number of surviving mice 6, 8, 10, and 15 days after infection. The test was performed on 12 animals in each group.

(Results)

[0412]

[Table 6] 目 Day 6 Day 8 Day 10 Day 15生理 Physiological saline only 200 Compound A 12 210 Compound 12 of Example 29 12 12 12 Compound of Example 34 12 12 11 10}

[0413]

The active ingredient of the present invention, 2-deoxy-
Since the 2,3-didehydro-N-acylneuraminic acid derivative (1) has excellent sialidase inhibitory activity and inhibits influenza virus replication, the present invention provides a sialidase inhibitor, a virus (particularly influenza virus) replication inhibitor Useful as

Further, when the 2-deoxy-2,3-didehydro-N-acylneuraminic acid derivative (1) is administered to an animal infected with influenza, an excellent infection treatment and prevention effect is exhibited. Therefore, the 2-deoxy-2,3 of the present invention
The composition containing the -didehydro-N-acylneuraminic acid derivative (1) as an active ingredient is useful as a medicament, and is useful as a prophylactic and therapeutic agent (preferably a therapeutic agent) for viral infections (particularly influenza). .

────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] February 25, 1999

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Claims

[Correction method] Change

[Correction contents]

[Claims]

Embedded image [ Wherein , R ¹ represents an alkyl group having 1 to 4 carbon atoms ;
R ² and R ³ are the same or different and each represent a hydrogen atom or
X represents a halogen atom;
Or an alkoxy group having 1 to 4 carbon atoms , Y is NH
Z represents _two groups , and Z represents an oxygen atom . Or a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Makoto Yamashita 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Inside Sankyo Co., Ltd. (72) Inventor Masami Arai 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Within Sankyo Co., Ltd.

Claims (15)

[Claims] 1. A compound of the general formula [Wherein, R ¹ represents an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom, and R ² and R ³ may be the same or different and are a hydrogen atom or an aliphatic group having 2 to 25 carbon atoms. X represents an acyl group, X represents a hydroxyl group, a halogen atom, R ^a O
A group ( ^Ra represents an aliphatic acyl group having 2 to 25 carbon atoms) or an alkoxy group having 1 to 4 carbon atoms, and Y represents an NH ₂ or R ^b R ^c N—O— group (R ^b And R ^c are the same or different and each represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms), and Z represents an oxygen atom or a sulfur atom. However, when Y is an NH ₂ group, X is a hydroxyl group or R ^a O—
A group ( ^Ra has the same meaning as described above), and
Compounds in which R ¹ is an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom and Z is an oxygen atom are excluded. Or a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. 2. The compound according to claim 1, wherein R ¹ is a methyl group which may be substituted by a fluorine atom, a pharmacologically acceptable salt thereof or a carboxylate thereof as an active ingredient. Prophylactic or therapeutic agent. 3. A prophylactic agent for influenza comprising the compound according to claim 1, wherein R ¹ is a methyl, monofluoromethyl or difluoromethyl group, a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. Or a therapeutic agent. 4. A prophylactic or therapeutic agent for influenza comprising the compound according to claim 1, wherein R ¹ is a methyl group, a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. 5. The compound according to claim 1, wherein R ² is a hydrogen atom or an aliphatic acyl group having 8 to 16 carbon atoms, a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. Prophylactic or therapeutic agent for influenza. 6. The compound according to claim 1, wherein R ² is an octanoyl, decanoyl, dodecanoyl, myristoyl or palmitoyl group, a pharmacologically acceptable salt thereof or an influenza containing the carboxylic acid ester thereof as an active ingredient. Prophylactic or therapeutic agents. 7. The compound according to claim 1, wherein R ³ is a hydrogen atom or an aliphatic acyl group having 8 to 16 carbon atoms, a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. Prophylactic or therapeutic agent for influenza. 8. The compound according to claim 1, wherein R ³ is a hydrogen atom or an octanoyl, decanoyl, dodecanoyl, myristoyl or palmitoyl group, a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. A preventive or therapeutic agent for influenza contained. 9. The compound according to claim 1, wherein R ² is an aliphatic acyl group having 8 to 16 carbon atoms, and R ³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof. Alternatively, a prophylactic or therapeutic agent for influenza comprising a carboxylic acid ester thereof as an active ingredient. 10. R ² is an octanoyl, decanoyl, dodecanoyl, myristoyl or palmitoyl group,
5. The prophylactic or therapeutic agent for influenza comprising the compound according to claim 1, wherein R ³ is a hydrogen atom, a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. 11. A prophylactic agent for influenza comprising the compound according to claim 1, wherein X is a fluorine atom, a methoxy group or an ethoxy group, a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. Or a therapeutic agent. 12. The prevention of influenza comprising the compound according to claim 1, wherein Y is NH ₂ or NH ₂ —O—, a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. Agent or therapeutic agent. 13. The method according to claim 1, wherein Y is an NH ₂ group.
And / or a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. 14. The method according to claim 1, wherein Z is an oxygen atom.
And / or a pharmaceutically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. 15. A prophylactic or therapeutic agent for influenza comprising the compound according to claim 1 selected from the following group, a pharmacologically acceptable salt thereof or a carboxylic acid ester thereof as an active ingredient. 5-acetamido-4-guanidino-2,3,4,5,7-pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid, 5-acetamido-4-guanidino-9- O-dodecanoyl-2,3,4,5,7-pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid, 5-acetamido-4-guanidino-9-O-myristoyl- 2,3,4,5,7-pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid, 5-acetamido-4-guanidino-9-O-hexadecanoyl-2, 3,4,5,7-pentadeoxy-7-fluoro-D-glycero-D-galacto-non-2-enopyranosonic acid, 5-acetamido-4-guanidino-2,3,4 , 5,7
-Pentadeoxy-7-methoxy-D-glycero-D-
Galacto-non-2-enopyranosonic acid, 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-non- 2-enopyranosonic acid, 5-acetamido-4-guanidino-9-O-decanoyl-2,3,4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopyranosonic acid 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopyranosonic acid, 5-acetamide -4-guanidino-9-O-myristoyl-2,3,4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopi Lanosonic acid, 5-acetamido-4-guanidino-9-O-hexadecanoyl-2,3,4,5,7-pentadeoxy-7-methoxy-D-glycero-D-galacto-non-2-enopyranosonic acid 5-acetamido-4-guanidino-2,3,4,5,7
-Pentadeoxy-7-ethoxy-D-glycero-D-
Galacto-non-2-enopyranosonic acid, 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadeoxy-7-ethoxy-D-glycero-D-galacto-non- 2-enopyranosonic acid, 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadeoxy-7-ethoxy-D-glycero-D-galacto-non-2-enopyranosonic acid 5-acetamido-4-guanidino-9-O-myristoyl-2,3,4,5,7-pentadeoxy-7-ethoxy-D-glycero-D-galacto-non-2-enopyranosonic acid, or -Acetamide-4-guanidino-9-O-palmitoyl-2,3,4,5,7-pentadeoxy-7-ethoxy-D-glycero-D-galacto-non-2 -Enopyranosonic acid.