JPH02256697A - Lipid a monosaccharide analog - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [either one of R<1> and R<4> is H, OH protecting group, etc., and the other is P(O)(OH)2; either one of R<2> and R<3> is 6-20C aliphatic acyl capable of containing OH, etc., and the other is 6-20C aliphatic acyl capable of containing halogen, etc., or 6-20C alkyl capable of containing OH, etc.; R<5> is H or OH-protecting group] or salt thereof. EXAMPLE:2-Deoxy-2-[(2'R,3'S)-2'-fluoro-3'-myristoyloxymyristoylamide]- 3-O- myristoyl-D-glucopyranosyl-4-phosphate. USE:An imminoactivator and antiulcer agent. PREPARATION:A glucosamine hydrochloride expressed by formula II is converted to an amide body thereof and the resultant amide body is reacted with an alcohol. Then the produced compound expressed by formula III (R<6> is silyl, etc.; R<7> is OH protecting group) is successively subjected to protection of diol, removal of the group R<6>, alkylation of an amino group located in 2-position, modification of OH located in 3-position and removal of the protecting group R<7> to provide a compound expressed by formula IV (R<8> to R<10> are protecting groups; R<3>' is R<3>, etc.), which is then deprotected.

Description

Detailed Description of the Invention [Objective] (Industrial Application Field) The present invention relates to a novel lipid A monosaccharide analog and its salt, which has an antitumor effect based on macrophage activation. ) The outermost layer of the cell wall of Gram-negative bacteria obtained from intestinal bacteria contains toxic components (endotoxin) that are not secreted outside the bacterial body. immune adjuvant activity related to self-defense, macrophage activity, mitogen activity, fever effect, tumor necrosis effect,
It exhibits various biological activities such as enhancing antibody production and inducing TNF.

Such endotoxin is composed of lipopolysaccharide, and it has been found that the so-called lipid A moiety is the active center of endotoxin activity.

On the other hand, as lipid A biosynthetic precursors, lipids X and Y, which are monosancharides, were isolated from E. coli mutant strains, and it has been revealed that these also exhibit the same activity as lipid A.

Based on these results, it was decided to synthesize derivatives of lipid A, X, or Y and examine their activities (for example, Tetrahedron L
ett, 26.1545 (1985) or Kiso et al., Carb.

hydrate research, 162.127
(1987)).

However, since it is a bacterial endotoxin itself, problems such as lethal toxicity, fever, decrease in white blood cells, and induction of autoimmune diseases remain.

(Problems to be Solved by the Invention) The present inventors have conducted extensive research over many years on the synthesis of lipid A monosaccharide analogs having macrophage activating effects and their pharmacological activities. A novel lipid A mono having a structure different from that of monosaccharide derivatives, that is, having an aliphatic acyl group having 6 to 20 carbon atoms substituted with a halogen atom and a hydroxyl group or an aliphatic acyloxy group having 6 to 20 carbon atoms. A saccharide analog or an alkyl group having 6 to 20 carbon atoms,
The present invention was completed based on the discovery that a novel lipid A monosaccharide analog having an ether bond at the 3-position hydroxyl group has an excellent macrophage activating effect and is useful as an immunostimulant or an antitumor agent.

[Constitution] The novel lipid A monosaccharide analog of the present invention has the following structure: [wherein, one of R1 and R4 is a hydrogen atom, and the formula -P
(0) (OH) represents a group having 2 or a hydroxyl group-protecting group, and the other represents a group having the formula -P (0) (OH) x.

Among R2 and R3, one represents an aliphatic acyl group having 6 to 20 carbon atoms, which may have a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 6 to 20 carbon atoms, and the other represents a halogen atom and an aliphatic acyl group having 6 to 20 carbon atoms. , hydroxyl group or carbon number 6
An aliphatic acyl group having 6 to 20 carbon atoms having 6 to 20 aliphatic acyloxy groups, or an aliphatic acyl group having 6 to 20 carbon atoms which may have a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 6 to 20 carbon atoms. represents an alkyl group.

R5 represents a hydrogen atom or a hydroxyl group protecting group.

In the above general formula (I), "hydroxyl group protecting group" in the definition of R1, R4 and R5
represents a protecting group in a reaction and a protecting group when administered to a living body, such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, lauroyl, myristoyl, tridecanoyl, balmitoyl,
Alkylcarbonyl groups such as stearoyl, halogenated alkylcarbonyl groups such as chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, lower alkoxyalkylcarbonyl groups such as methoxyacetyl, (E)-2-methyl-2- Aliphatic acyl groups such as unsaturated alkylcarbonyl groups such as butenoyl; arylcarbonyl groups such as benzoyl, α-naphthoyl, β-naphthoyl, 2-bromobenzoyl, 4
- halogenated arylcarbonyl groups such as chlorobenzoyl, lower alkylated arylcarbonyl groups such as 2.4.6-trimethylbenzoyl, 4-toluoyl,
Lower alkoxylated arylcarbonyl groups such as 4-anisoyl, nitrated arylcarbonyl groups such as 4-nitrobenzoyl, 2-nitrobenzoyl, lower alkoxycarbonylated arylcarbonyl groups such as 2-(methoxycarbonyl)benzoyl, 4- Aromatic acyl groups such as arylated arylcarbonyl groups such as phenylbenzoyl; tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl
a tetrahydropyranyl or tetrahydrothiopyranyl group such as yl, 4-methoxytetrahydrothiopyran-4-yl; a tetrahydrofuranyl or tetrahydrothiofuranyl group such as tetrahydrofuran-2-yl, tetrahydrothiofuran-2-yl; trimethylsilyl,
triethylsilyl, isopropyldimethylsilyl, t-
Butyldimethylsilyl, methyldiisopropylsilyl,
Tri-lower alkylsilyl groups such as methyldi-butylsilyl and triisopropylsilyl; tri-substituted tri-lower alkylsilyl groups such as methyldi-butylsilyl and triisopropylsilyl, and tri-substituted aryl groups such as diphenylmethylsilyl, diphenyl-1-butylsilyl, diphenylisopropylsilyl, and phenyldiisopropylsilyl; Silyl groups such as lower alkylsilyl groups; methoxymethyl, 1,1-
Lower alkoxymethyl groups such as dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t-butoxymethyl, lower alkoxylated lower alkoxymethyl groups such as 2-methoxyethoxymethyl, 2, 2. Alkoxymethyl groups such as halogenated lower alkoxymethyl such as 2-trichloroethoxymethyl and bis(2-chloroethoxy)methyl; 1-ethoxyethyl, 1-methyl-1-methoxyethyl, 1-(isopropoxy) Substituted ethyl groups such as lower alkoxylated ethyl groups such as ethyl, halogenated ethyl groups such as 2,2.2-trichloroethyl, and arylzelenylated ethyl groups such as 2-(phenylzelenyl)ethyl; benzyl, phenethyl, 3 - lower alkyl groups substituted with 1 to 3 aryl groups such as phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl.

4-methylbenzyl, 2.4.6-trimethylbenzyl, 3,4.5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-glorobenzyl, Aryl ring substituted with lower alkyl, lower alkoxy, nitro, halogen, cyano groups such as 4-bromobenzyl, 4-cyanopencyl, 4-cyanobensylphenylmethyl, bis(2-nitrophenyl)methyl, piperonyl Aralkyl groups such as lower alkyl groups substituted with 1 to 3 aryl groups: lower alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, isobutoxycarbonyl,
Alkoxycarbonyl groups such as lower alkoxycarbonyl groups substituted with halogen or tri-lower alkylsilyl groups such as 2,2.2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl; alkenyls such as vinyloxycarbonyl and allyloxycarbonyl; Oxycarbonyl group; benzyloxycarbonyl,
The aryl ring is substituted with one or two lower alkoxy or nitro groups, such as 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl. an optional aralkyloxycarbonyl group; a protecting group in reactions such as an allyl group;
Formula -COCH□CH2C00H1-COCH2CH(O
Examples include an acyl group having a terminal carboxy group, such as a compound having f()COOH or -COCH=CH-COOH, or a protective group when administered to a living body, such as pivaloyloxymethyloxycarbonyl.

The "aliphatic acyl group having 6 to 20 carbon atoms" in the "aliphatic acyloxy group having 6 to 20 carbon atoms" and "aliphatic acyl group having 6 to 20 carbon atoms" in the definitions of R2 and R3 is as follows: For example, pentylcarbonyl, hexylcarbonyl, heptylcarbonyl, octylcarbonyl, nonylcarbonyl, decylcarbonyl, 3-methylnonylcarbonyl, 8-methylnonylcarbonyl, 3-ethyloctylcarbonyl, 3,7-dimethyloctylcarbonyl, undecylcarbonyl, Dodecylcarbonyl, tridecylcarbonyl, tetradecylcarbonyl, pentadecylcarbonylcarbonyl, 1-methylpentadecylcarbonyl 14-methylpentadecylcarbonyl, 13,13-dimethyltetradecylcarbonyl, heptadecylcarbonyl, 15
-Methylhexadecylcarbonyl, octadecylcarbonyl, 1-methylheptadecylcarbonyl and nonadecylcarbonyl can be mentioned, but straight-chain or branched-chain aliphatic acyl groups having 10 to 16 carbon atoms are preferred.

The "halogen atom" in the definition of R2 and R3 represents fluorine, chlorine, bromine or iodine.

Examples of "alkyl group having 6 to 20 carbon atoms" in the definition of R3 include hexyl, 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-methylheptyl, 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, 3-ethyloctyl, 3,7-dimethyloctyl, 7,7-dimethyloctyl, undecyl, 4,8-dimethylnonyl, dodecyl, tridecyl, tetradecyl, pentadecyl, 3,7.
11-trimethyldodecyl, hexadecyl, 4,8,1
2-trimethyltridecyl, 1-methylpentadecyl,
14-methylpentadecyl, 13,13-dimethyltetradecyl, heptadecyl, 15-methylhexadecyl,
Octadecyl, 1-methylheptadecyl, nonadecyl,
Examples include eicosyl and 3,7,II,15-tetramethylhexadecyl, preferably those having 10 carbon atoms.
1 to 16 straight or branched alkyl groups.

Compound (I) of the present invention can be made into a salt, preferably an alkali metal or alkaline earth metal salt such as a sodium salt, potassium salt or calcium salt; triethylamine salt. , salts of organic bases such as trimethylamine salts.

Compound (I) of the present invention has an asymmetric carbon in the molecule and exists in stereoisomers each having an S configuration and an R configuration. included in

In compound (I), suitable compounds include (1)
R' and R4 are the same or different hydrogen atoms or the formula -P
(0) A compound having a group having (OH)2 (2) Among R' and R4, one is a group having a formula -P(0)(OH)z, and the other is a hydrogen atom or a group having a formula -p (0) (OH) A compound (3) of R'' and R3, one of which may have a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 10 to 16 carbon atoms; Compound (4) having 10 to 16 aliphatic acyl groups, the other being an aliphatic acyl group having 10 to 16 carbon atoms and having a halogen atom and a hydroxyl group or an aliphatic acyloxy group having 10 to 16 carbon atoms R2 is a halogen atom, a hydroxyl group, or a carbon number 1
Compound (5) R3, which is an aliphatic acyl group having 10 to 16 carbon atoms, which may have 0 to 16 aliphatic acyloxy groups, is a halogen atom, a hydroxyl group, or a halogen atom, a hydroxyl group, or
Compound (6) R5, which is an alkyl group having 10 to 16 carbon atoms which may have 0 to 16 aliphatic acyloxy groups, is a hydrogen atom or a compound with the formula -COCHzCHzCO
OHl-COCH2CH(OH)COOH or -C
Mention may be made of compounds which are acyl groups with a terminal carboxy group, such as groups with OCH=CH-COOH.

Representative compounds of the present invention include, for example, the compounds listed in Table 1A, Table 1B, Table 2A, and Table 2B, but the present invention is not limited to these compounds. .

Table 1A Table 2B Table 1B Table 2A Table 2B Glucosamine (iI) can be produced using as a starting material.

[Method A] [Isu] Among the above exemplary compounds, preferred compounds include IA-
12, 15, 39, 43, 44, 67, 69, 70, 7
1,92,93,94,96゜97.98J10,11
1,112,115,116,119,120,121
,124°125.130,139,145,146,
147.1B-1, 2, 3, 4, 21, 22, 23, 2
7,29,33,34,35,43,44゜45.50
,52,54,59,50,63,65,68,70,
72, 74.2A-9, 10, 11, 12, 53, 54
,63,64,67,68,77,84,2B-2,3
,4,9,10,11,14,15,19,20,28
,29,34,35°36.38,40,42,43,
45, 47, 48, 49, 50, 51, 52, 53, 5
4,55°56.57,58,59,60,61,62
, 63, 64, and 65.

Furthermore, suitable compounds include IA-12,39,67,93,120,145,14
7,1B-3,21,29,33,43,52,54,
65, 70, 72, 74, 2A-10, 54, 63, 7
7,84,2B-3,10,14,19,42,43,
45, 47, 48, 49, 50, 58, 59°63.6
5 compounds can be mentioned.

Lipid A monosaccharide analogs of the present invention can be obtained from known compounds [III'] by the method described below.
) (IX) R (XI) [Method B] (XII) (XIII) (1,, III'') [Method A] produces a compound in which a phosphoric acid residue is bonded to the 1st position of the compound of the present invention. It's a method.

[Method B] is a method for producing a compound in which a phosphoric acid residue is bonded to the 4-position of the compound of the present invention.

In the above formula, R2 and R3 have the same meanings as above.

R'' and R3/ / / are a halogen atom, a hydroxyl group, R
1, an aliphatic acyl group having 6 to 20 carbon atoms which may have a hydroxyl group protected by a "hydroxyl protecting group" or an aliphatic acyloxy group having 6 to 20 carbon atoms in the definition of R4 or R5; Halogen atom and hydroxyl group, R1,
A hydroxyl group protected with a "hydroxyl protecting group" in the definition of R4 or R5 or an aliphatic acyl group having 6 to 20 carbon atoms having an aliphatic acyloxy group having 6 to 20 carbon atoms; or a halogen atom, a hydroxyl group, R1 , an alkyl group having 6 to 20 carbon atoms, which may have a hydroxyl group protected by a "hydroxyl protecting group" or an aliphatic acyloxy group having 6 to 20 carbon atoms in the definition of R4 or R5.

R'' is a halogen atom, a hydroxyl group, a hydroxyl group protected with a "hydroxyl protecting group" in the definition of R1, R4 or R5, or a C6-20 aliphatic acyloxy group having 6-20 carbon atoms; Aliphatic acyl group or
A halogen atom, a hydroxyl group, a hydroxyl group protected with a "hydroxyl protecting group" in the definition of R1, R4 or R5, or a C6-20 aliphatic acyloxy group having 6-20 carbon atoms. Indicates an aliphatic acyl group.

R3″ is a halogen atom, a hydroxyl group, a hydroxyl group protected with a “hydroxyl protecting group” in the definition of R1, R4, or R5, or a C6-C2 aliphatic acyloxy group having 6 to 20 carbon atoms; 20 to 20 alkyl groups.

R6 represents, for example, an amine protecting group such as the aliphatic acyl group; the aromatic acyl group; the alkoxycarbonyl group; the alkenyloxycarbonyl group; the aralkyloxycarbonyl group; the silyl group or the aralkyl group. .

R7 and R'' are the same or different, R1, R4 and R5
Refers to the same group as "hydroxyl group protecting group" in the definition.

. R8 and R9 are the same or different, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, S-butyl, t-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, n- hexyl, 4-methylpentyl, 3-methylpentyl, 2-
1 carbon number such as methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, ■, 1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl Mention may be made of linear or branched alkyl groups having 6 to 6 carbon atoms or aryl groups having 5 to 12 carbon atoms, such as phenyl and naphthyl. In addition, this aryl group may have on the ring one to four substituents selected from the following, and the substituents on the ring include an amino group; a nitro group; a cyano group; Lower alkyl, a carboxy group optionally substituted with the halogenated lower alkyl described below or the aralkyl; carbamoyl group; the halogen atom; the lower alkyl group:; trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl,
2,2.2-trichloroethyl, 2,2゜2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2
Examples include halogenated lower alkyl groups such as -fluoroethyl and 2,2-dibromoethyl, and the aforementioned aliphatic acyl groups, and preferably a halogen atom or a halogenated lower alkyl group.

R'' and R1'L are the same or different and represent a protecting group for a phosphoric acid group such as the aryl group or the aralkyl group.

Step ↓ is to convert glucosamine hydrochloride (II) into trifluoroacetic acid and dicyclohexylcarbodiimide (DCC).
), trifluoroacetic anhydride and triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, 1,5-diazabicyclo[4 ,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane, ■,8-diazabisiglo[5,4,0]undec-7-ene (DBU). This is a process for producing the amide compound (III) by reacting a trifluoroacetic acid ester such as ethyl trifluoroacetate with the above-mentioned organic base.

The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably halogenated hydrocarbons such as methylene chloride and chloroform; ether, tetrahydrofuran, Ethers such as dioxane and dimethoxyethane; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, and isoamyl alcohol; dimethylformamide,
Amides such as dimethylacetamide and hexamethylphosphorotriamide; and sulfoxides such as dimethylsulfoxide can be mentioned.

The reaction temperature is 0°C to 100°C, preferably room temperature, and the reaction time varies mainly depending on the reaction temperature, the raw material compound, or the type of solvent used, but is usually 0°C to 100°C.
The duration is from 1 hour to 24 hours.

In the chopstick λ step, the amide compound (III) is reacted with an alcohol having the general formula R70H (for example, methanol, ethanol, benzyl alcohol, allyl alcohol) under an acid catalyst to form a glycosidic bond to produce a compound (■■). This is the process of

As the solvent, an alcohol having the general formula R70H, which is a reaction reagent, is used in large excess.

The acid to be used is not particularly limited as long as it is normally classified as an acid, but suitable examples include mineral acids such as hydrochloric acid and sulfuric acid, and organic acids such as para-toluenesulfonic acid. The above-mentioned acids can also be used.

The reaction temperature is 0°C to 200°C, preferably reflux temperature, and the reaction time mainly depends on the reaction temperature, the raw material compound, or the type of solvent used.
Usually 0.1 to 24 hours.

In step 1, the alcohols at the 4- and 6-positions of compound (IV) are protected with diols such as isopropylidene, benzylidene, or ethylidene in a solvent under an acid catalyst to form compound (V). This is a manufacturing process.

The reagent used for protecting diols is not particularly limited as long as it is normally used for protecting diols, but preferably aldehyde derivatives such as benzaldehyde, ketone derivatives such as acetone, Mention may be made of dimethoxy compounds such as 2,2-dimethoxypropane and dimethoxybenzyl.

The solvent is not particularly limited as long as it does not inhibit the reaction, but suitable solvents include halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as dioxane and tetrahydrofuran, and carbonized solvents such as hexane and pentane. Examples include hydrogens, aromatic hydrocarbons such as benzene and toluene, esters such as ethyl acetate, and polar solvents such as dimethylformamide and acetone.

The acid catalyst used is not particularly limited as long as it is commonly used as an acid, but preferably organic acids such as para-toluenesulfonic acid, camphorsulfonic acid, and pyridium paratoluenesulfonate, or inorganic acids such as hydrochloric acid. can be mentioned.

The reaction temperature varies depending on the acid catalyst, raw material compound, etc. used, but is usually carried out at 0 to 100°C, and the reaction time mainly varies depending on the reaction temperature, raw material compound, or type of solvent used. , usually 0. I hours to 24 hours.

! In the step, R6 group of compound (V) is removed to form compound (V).
This is a process for producing I).

When a silyl group is used as the R6 group, it is usually removed by treatment with a compound that generates a fluorine anion, such as tetrabutylammonium fluoride. The reaction solvent is not particularly limited as long as it does not inhibit the reaction, but ethers such as tetrahydrofuran and dioxane are preferred. The reaction temperature and reaction time are not particularly limited, but the reaction is usually carried out at room temperature for 10 minutes to 18 hours.

When the R6 group is an aliphatic acyl group, aromatic acyl group or alkoxycarbonyl group, it can be removed by treatment with a base in the presence of an aqueous solvent or by reduction. The base is not particularly limited as long as it does not affect other parts of the compound, but preferably alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium hydroxide, and potassium hydroxide. It is carried out using alkali metal hydroxide or concentrated ammonia-methanol. The solvent used is not particularly limited as long as it is used in ordinary hydrolysis reactions, and water or water and alcohols such as methanol, ethanol, and n-propanol, or ethers such as tetrahydrofuran and dioxane are used. A mixed solvent with an organic solvent such as is suitable. The reaction temperature and reaction time vary depending on the starting materials, the base used, etc. and are not particularly limited, but in order to suppress side reactions, they are usually at 0°C to 150°C for 1 to 10 hours.

Removal by reduction is carried out using a reducing agent such as sodium borohydride according to a conventional method.

When the R6 group is an aralkyl group or an aralkyloxycarbonyl group, it is preferable to remove it by catalytic reduction at room temperature using a catalyst such as platinum or palladium on carbon.

The solvent used in removal by catalytic reduction is not particularly limited as long as it does not participate in this reaction, but alcohols such as methanol, ethanol, and isopropanol, and ethers such as diethyl ether, tetrahydrofuran, and dioxane are used. , aromatic hydrocarbons such as toluene, benzene, and xylene, aliphatic hydrocarbons such as hexane and cyclohexane, esters such as ethyl acetate and propyl acetate, fatty acids such as acetic acid, or these organic solvents. A mixed solvent with water is preferred. The catalyst to be used is not particularly limited as long as it is normally used in the catalytic reduction reaction, but palladium carbon, Raney nickel, platinum oxide, platinum black, and rhodium-carbon are preferably used.
Aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate are used.

The pressure is not particularly limited, but the pressure is usually 1 to 10 atm.

The reaction temperature and reaction time vary depending on the starting materials and the type of catalyst, but are usually 5 minutes to 2 minutes at 0°C to 100°C.
It will be held for 4 hours.

When the R6 group is an alkenyloxycarbonyl group,
Usually, it can be removed by treatment with a base under the same conditions as the removal reaction when the protecting group for the amino group is an aliphatic acyl group, an aromatic acyl group, or a lower alkoxycarbonyl group. In the case of allyloxycarbonyl, removal using palladium and triphenylphosphine or nila quertetracarbonyl is particularly simple and can be carried out with fewer side reactions.

! The step is a step of producing compound (VII) by acylating or alkylating the 2-position amino group of compound (VI).

As a method for acylation, a carboxylic acid having the general formula R'''OH [wherein R2'' represents the same group as the acyl residue in the definition of R'' above] is converted into dicyclohexylcarbodiimide (DCC). , an acylating agent R'''X (wherein R2'' has the same meaning as above, and X is
Groups having the general formula OR"': halogen atoms such as chlorine, bromine, iodine; alkylcarbonyloxy groups such as ace-1-hexy, propionyloxy, taloloacetyloxy, dichloroacetyloxy, 1-dichloroacetyloxy, Halogenated alkylcarbonyloxy groups such as trinoloacetyloxy, lower alkoxyalkylcarbonyloxy groups such as methoxyacetyloxy, unsaturated alkylcarbonyloxy groups such as (E)-2-methyl-2-butenoyloxy, etc. aliphatic acyloxy group; arylcarbonyloxy group such as benzoyloxy, halogenated arylcarbonyloxy group such as 2-bromobenzoyloxy, 4-chlorobenzoyloxy, 2,4.6-trimethylbenzoyloxy,
Lower alkylated arylcarbonyloxy groups such as 4-toluoyloxy, lower alkoxylated arylcarbonyloxy groups such as 4-anisoyloxy, nitrated arylcarbonyls such as 4-nitrobenzoyloxy, 2-nitrobenzoyloxy Aromatic acyloxy groups such as oxy groups; trihalogenomethyloxy groups such as trichloromethyloxy; lower alkanesulfonyloxy groups such as methanesulfonyloxy and ethanesulfonyloxy; nitrifluoromethanesulfonyloxy and pentafluoroethanesulfonyloxy; It represents a leaving group such as a halogeno lower alkanesulfonyloxy group; an arylsulfonyloxy group such as benzenesulfonyloxy and P-toluenesulfonyloxy. ) in a solvent in the presence of a base.

The solvent is not particularly limited as long as it does not inhibit the reaction, but suitable examples include halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride, ethers, ethers such as dioxane, and tetrahydrofuran, and hexane. Examples include hydrocarbons such as benzene, aromatic hydrocarbons such as toluene, esters such as ethyl acetate, and polar solvents such as dimethyl sulfoxide and dimethylformamide.

The base used may preferably include organic bases, such as triethylamine, pyridine, DB
U, DBN, N, N-dimethylaniline, N2N-
They are diethylaniline and N,N-dimethylaminopyridine.

The reaction temperature is 0°C to 100°C, preferably 20°C to 50°C, and the reaction time varies mainly depending on the reaction temperature, the raw material compound, or the type of solvent used, but is usually 0°C to 100°C. The duration is from 1 hour to 24 hours.

As a method of alkylation, activated alkylating agent R
""-X' (in the formula, R2/// represents the same group as the alkyl residue in the definition of R2' above, X' is a halogen atom in the definition of X; aliphatic acyloxy group; aromatic acyloxy Group; lower alkanesulfonyloxy group:
Indicates a leaving group such as a halogeno lower alkanesulfonyloxy group; an arylsulfonyloxy group. ) in a solvent in the presence of a base.

The solvent is not particularly limited as long as it does not inhibit the reaction, but suitable examples include halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride, ethers, ethers such as dioxane, and tetrahydrofuran, and hexane. Examples include hydrocarbons such as benzene, aromatic hydrocarbons such as toluene, esters such as ethyl acetate, and polar solvents such as dimethyl sulfoxide and dimethylformamide.

The base used is preferably an inorganic base such as alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal carbonates such as potassium carbonate and sodium carbonate, or triethylamine, pyridine, and DBU.
-DBN, N,N-dimethylaniline, N,N-diethylaniline, N,N-dimethylaminopyridine organic bases may be mentioned, for example.

The reaction temperature is 0°C to 100°C, preferably room temperature, and the reaction time mainly varies depending on the reaction temperature, raw material compound, or type of solvent used, but is usually 1 hour to 1 day. be.

The step is to modify the 3-position hydroxyl group of compound (VII) with an R'' group in the same manner as the acylation of the amino group in the fifth step to produce compound (VIII').

In step 1, the protecting group R7 at the 1-position of compound (VIII') is
This is a step of removing the group to produce compound (IX).

R7 group is a silyl group, an aralkyloxycarbonyl group,
When the R is an aralkyl group, an aliphatic acyl group, an aromatic acyl group, an alkoxycarbonyl group, an alkoxymethyl group, or a substituted ethyl group,
The removal method is carried out in accordance with the removal method when six groups are the relevant groups.

When R'/group is a tetrahydropyranyl group, a tetrahydrofuranyl group, etc., it can be removed by treatment with an acid in a normal solvent.

The acid used is preferably hydrochloric acid, acetic acid-sulfuric acid, para-toluenesulfonic acid or acetic acid.

The solvent to be used is not particularly limited as long as it does not participate in this reaction, but alcohols such as methanol and ethanol; ethers such as tetrahydrofuran and dioxane, or a mixed solvent of these organic solvents and water may be used. suitable.

The reaction temperature and reaction time vary depending on the starting materials and the type of acid used, but are usually 0°C to 50°C and 10 minutes to 18 hours.

When the R7 group is an alkenyloxycarbonyl group, it is usually eliminated by treatment with a base under the same conditions as the removal reaction when the R7 group is an aliphatic acyl group, an aromatic acyl group, or an alkoxycarbonyl group. can be done. In the case of allyloxycarbonyl, removal using palladium and triphenylphosphine or nickel tetracarbonyl is particularly convenient and can be carried out with fewer side reactions.

When the R7 group is an allyl group, preferably in a solvent,
It can be removed by carrying out a reaction in the presence of a catalyst to shift the double bond into an enol ether type, and immediately adding pyridine-iodine-water.

The solvent is not particularly limited as long as it does not inhibit the reaction, but suitable examples include halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride, ethers, ethers such as dioxane, and tetrahydrofuran, and hexane. Examples include hydrocarbons such as benzene, aromatic hydrocarbons such as toluene, esters such as ethyl acetate, and polar solvents such as dimethyl sulfoxide and dimethylformamide.

Catalysts used include palladium catalysts such as palladium chloride, palladium acetate, rhodium hornworm catalysts such as 1,5-cyclooctadiene-bis[methyldiphenylphosphine rhodium hexafluorophosphate, rhodium acetate, 1 , 5-cyclooctadiene-bis[methyldiphenylphosphine coiridium hexafluorophosphate, and other iridium catalysts.

The reaction temperature varies depending on the catalyst, solvent, etc. used, but
It is usually carried out at a temperature of 0 to 100°C.

The reaction time varies depending on the reaction temperature in addition to the above, but is usually 1 to 5 hours.

In step 1, compound (IX) 1 obtained in this way is
This is a step of phosphorylating the hydroxyl group to produce compound (X).

Phosphorylation is carried out by forming an anion with a base in a solvent followed by reaction with a phosphorylating agent.

The solvent is not particularly limited as long as it does not inhibit the reaction, but suitable examples include ethers such as ether, dioxane, and tetrahydrofuran, and halogenated hydrocarbons such as chloroform and methylene chloride.

The base used is not particularly limited as long as it normally forms an anion, but preferably a lithium compound such as n-butyllithium, phenyllithium, or DB.
Organic bases such as U, DBN, DMAP, triethylamine, pyridine may be mentioned.

As the phosphorylating agent, reagents commonly used for phosphorylation such as dibenzyl chlorophosphate and diphenyl chlorophosphate are used.

The reaction temperature is -78 to 50°C, preferably -78°C to room temperature, and the reaction time mainly varies depending on the reaction temperature, raw material compound, or type of solvent used, but is usually 10 minutes. The period is from 24 hours to 24 hours.

In step 1, the protecting group of compound (X) is removed, and the compound (X
I), and if desired, the protecting group of the R'' group is removed.

In principle, the reactions for removing protective groups for phosphoric acid residues and the reactions for removing protective groups for hydroxyl groups differ depending on the type of protecting group, but the desired removal reactions can be carried out sequentially in any order. In some cases, the protecting group for the phosphoric acid residue is removed at the same time when the protecting group is removed, but in general,
It is preferred that the protecting group R1° of the phosphoric acid residue is removed last. This is because it is easy to handle.

For example, when the R" group is an aralkyl group such as benzyl, catalytic reduction is performed at -78°C to 0°C under a palladium carbon catalyst to convert R2 and/or R" into a hydroxyl-protecting group. All protecting groups, if present, can be removed at once, and if the R10 group is an aryl group such as a phenyl group, after catalytic reduction under palladium on carbon catalyst, further platinum oxide catalyst This is carried out by performing a catalytic reduction below.

In addition, in some cases (for example, in the case of acetonide), the protecting group in which the R8 and R9 groups are part is removed by purification by silica gel chromatography, but usually it is removed by hydrous acetic acid, or tetrahydrofuran,
In solvents such as ethers such as dioxane, alcohols such as ethanol and methanol, dilute hydrochloric acid, dilute sulfuric acid,
0 to 100 using hydrous paratoluenesulfonic acid as a catalyst
Remove at ℃.

In addition, when obtaining a water-soluble salt of phosphoric acid, it can be obtained by washing with an inorganic acid diluted with water such as diluted hydrochloric acid, dissolving it in a solvent such as chloroform, and adding a base.

The process is a process of alkylating the 3-position hydroxyl group of compound (V) with R3'' group to produce compound (X, TI).

The alkylation method is carried out in the same manner as in the fifth step.

The first step is a step of removing the protecting group R6 of the amino group at the 2-position of compound (XII) to produce compound (XIII), and is carried out in the same manner as the fourth step.

Marquis Yosue said that the amino group at the 2-position of compound (XIII) was
According to the fifth step, the compound (VIII'
') is the process of manufacturing.

The produced compound (VIII") can be subjected to the seventh to ninth steps to produce a compound corresponding to compound (XI).

In the J step, compound (VIII) [compound (VII
I') or compound (VIII'')] to produce compound (XIV), and is carried out according to the ninth step.

Shaving is a process of protecting the 6-position hydroxyl group of compound (XIV) with an R'' group to produce compound (XV).

The primary hydroxyl group at position 6 is replaced with a compound having the general formula R11x (
In the formula, R'' and X have the same meanings as above, for example, C, L
CH20CH:>, CICHzOCH2C6Hs, Br
CH20CH2CsHs, CIC02C1kC6H5,
In CIC (hclbccli can be mentioned),
-50 to 50°C in a solvent (for example, methylene chloride, chloroform, halogenated hydrocarbons such as carbon tetrachloride, ethers such as ether, dioxane, tetrahydrofuran, hydrocarbons such as hexane, benzene, aromatic hydrocarbons such as toluene, esters such as ethyl acetate, polar solvents such as dimethylsulfoxide, dimethylformamide, acetone), bases (e.g. DBU, DBN, DMAP, DABCO, pyridine, triethylamine, aniline, N,N-dimethylaniline, N,N-diethylaniline) or in a solvent (e.g. acetone, tetrahydrofuran, dioxane), a base (e.g. sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate) It can be produced using an aqueous solution of.

The step is a step of phosphorylating the hydroxyl group at the 4-position of compound (XV) to produce compound (XVI), and is carried out according to the eighth step.

The nail ↓dan step is a step of removing the protecting group of compound (XVI) to produce compound (XVII), and the removal of the hydroxyl group protecting groups R7 and R'' is carried out according to the seventh step,
If there is a hydroxyl-protecting group on R'' and/or R3/ / /, the removal of that protecting group and the phosphoric acid residue-protecting group R'' is carried out according to the ninth step. As described in the process, it is preferable to devise conditions so that the protecting group R'' of the phosphoric acid residue is removed last.

In Step 2, the protecting group for the hydroxyl group at position 1 of compound (X'!I) was selectively removed according to the 7th step, and the hydroxyl group at the 1st position was phosphorylated according to the 8th step. Then, if there is a hydroxyl protecting group on the hydroxyl protecting group R1, R" and/or R3 //, remove that protecting group and the phosphoric acid residue protecting group R" according to step 16. This is a process for producing compound (XVIII).

[Effect] The novel lipid A monosaccharide analog of the present invention has an excellent macrophage activating effect and has low toxicity, so it is useful as an immunostimulant or an antitumor agent.

Examples of the administration form of the compound (I) of the present invention include oral administration in the form of tablets, capsules, granules, powders, syrups, etc., and parenteral administration in the form of injections or severe punishment. These preparations are manufactured by well-known methods using additives such as excipients, binders, disintegrants, lubricants, stabilizers, and flavoring agents. The amount of use depends on the symptoms,
It varies depending on age, etc., but 0.01-50mg/kg per day
The body weight can be administered to adults usually once a day or in several divided doses.

The present invention will be explained in more detail below by giving examples.

Example 1 D-(+)-glucosamine hydrochloride 160 g (0°742
mol) in 2200 ml of methanol (99.6%) and 187.9 g (1.86 mol) of triethylamine.
Add l). Furthermore, 115.9 g of ethyl trifluoroacetate was added dropwise under water cooling, and the mixture was stirred overnight at room temperature. Concentrate under reduced pressure, benzene 250ml x 2, ethyl acetate 250ml
n+1 was added one after another, concentrated under reduced pressure, and further dried thoroughly using a vacuum pump.

The crude trifluoroacetyl compound obtained here was proceeded to the next step without being purified.

1(b) Al Z--oxy-2-rfluoroacetamide To the crude trifluoroacetyl compound obtained in Example 1(a),
Add 1850ml of 2% hydrochloric acid-allyl alcohol solution 3
The mixture was heated to reflux for 0 minutes. Cool to around 50℃ with ice water,
It was filtered through Celite. The filtrate was concentrated and further dried thoroughly using a vacuum pump.

The crude allyl ether obtained here was proceeded to the next step without being purified.

The crude allyl ether obtained in (a)-1(b) was converted into N, N-
Dissolve in 740 ml of dimethylformamide and add 2,2-
370 ml of dimethoxypropane was added, followed by 7.5 g of pyridinium p-toluenesulfonate, and the mixture was stirred at room temperature overnight. It was concentrated under reduced pressure and diluted with ethyl acetate. The precipitate was removed by filtration, and the filtrate was washed with aqueous sodium bicarbonate, water, and brine. It was dried over anhydrous magnesium sulfate, filtered through Celite and activated carbon, and concentrated. The residue was applied to a silica gel column using cyclohexane:ethyl acetate = 3 = 2 to separate and purify 80.5 g and 77.3 g of those with α and β ether bonds at the 1st position, respectively. It was done. Both α-form and β-form can be used in subsequent reactions.

[α-allylic body mass spectrum 282, 256.240° 101° [β-Allyl form] mass spectrum 280, 256.240° 126, 114.　LOI.

M/Z; 356 [M”+1], 340.298°2
22, 211.193.168.126. 109゜M
/Z; 356[1(”+1], 340.298°2
22, 211.193.168.155.145゜1(
d) 10 g of the trifluoroacetyl compound obtained in 1(c),
Dissolved in 200 ml of ethanol (99,5%), IN
100 nil of an aqueous sodium hydroxide solution was added thereto, and the mixture was heated under reflux for 4 hours. It was concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with water and brine, and anhydrous ml
It was dried with magnesium acid. After filtration, ethyl acetate was distilled off under reduced pressure, and the remaining oil was applied to a silica gel column.
Purification with ethyl acetate yielded 6.6 g (90.5%) of the target compound.

NMR spectrum (60MH2) (CDC13) δp
pm 1.43 (3H, s); 1.52 (3H, s);
2.40 (3H, broad); 2.6-4.6 (
9H, m); 5.05-6.35 (3H, m).

Elemental analysis (Ct□H2□NOs” 259.302 and (
7) Carbon Hydrogen Nitrogen Theoretical value 55.58 8,16 5.40 Analysis value 5
5.37 8.05 5.401(e) 5 g of the compound obtained in 1(d) (19,3 aunol
) was dissolved in 150 ml of methylene chloride, 6.8 g of (R)-3-benzyloxymyristic acid was added, and further 4.79 g of N,N'-dicyclohexylcarbodiimide was added.
g was added thereto, and the mixture was stirred at room temperature for 1 hour. It was filtered, concentrated under reduced pressure, and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. Filter and remove ethyl acetate under reduced pressure.
The residue is 1. Applied to silica gel column, cyclohexane:
Purification with ethyl acetate 1:1 yielded 5.33% of the target compound.
g (48%).

Infrared absorption spectrum νmax (KBr) 3510,
3280.1643.1550 cm-'NMR spectrum (270MHz) (CDC13) δppm0.
88 (3H, t, J=6.9 Hz); 1.20-1
．． 41 (1,8H, m); 1.45 (3H, s);
1.52 (3H, s); 1.56-1.70 (2H,
m); 2.43 (LH.

d, d, J = 6.9, 15.4 Hz); 2.56 (
IH, d, d, J=3.7, 15.0Hz); 3.1
9-3.29 (IH, m); 3.46-3.63 (2
H, m); 3.75-3.94 (5H, m); 4.
1&-4,24(IH,m); 4.36(IH,d,
J=2.6Hz); 4.45-4.62(3H, +n
); 5.12-5.26 (2H, m); 5.70-
5.88 (IH, m); 6.72 (IH, d, J=5
．． 9 Hz, NH); 7.30-7.37 (5H, m
) - 1(f) Allyl 2-deoxy-2-3'R)-3'-benzyloxymyristoylamide-3-0-2"R53'SR
-2'-Flow 3"-Beg. 1 g (1,74
mn+ol) was dissolved in 80 ml of methylene chloride, and (±
) 828 mg of -5yn-=-2=fluoro-3-benzyloxycarbonyloxymyristic acid was added, and further 359 mg of N,N'-dicyclohexylcarbodiimide and 255 mg of 4-dimethylaminopyridine were added sequentially, and the mixture was heated to room temperature. The mixture was stirred for 1 hour. It was filtered, concentrated under reduced pressure, and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with cyclohexane:ethyl acetate 5:1 to obtain the target compound at 1.2
Obtained with a yield of 2 g (73.6%).

Elemental analysis (CssHa4FNO□□・H20=972.
286) Carbon Hydrogen Nitrogen Fluorine Theoretical value 67.94 8.96 1.44 1.95
Analysis value 67.79 8.98 1.40 1.96
Infrared absorption spectrum νmax (film) 3290
, 1750.1655 cm-1 NMR spectrum (
60MHz) (CDC13) δPPm0.66-2.
43 (57H, n+); 3.12-6.53 (17H
, m [including 4,98(2H,s)]); 7.28(
Compound 380 rn obtained with IOH, 5)-1(f)
g was dissolved in 20 rnl of dried tetrahydrofuran, 17 mg (5% m01) of 1,5-cyclooctadiene-bis[methyldiphenylphosphinecoiridium hexafluorophosphate was added, and the inside of the reaction vessel was replaced with nitrogen. and further hydrogen substitution. After confirming that the color of the liquid changed from red to colorless, the atmosphere was immediately replaced with nitrogen.

After stirring at room temperature for 3 hours, 2 ml of water, 200 ml of iodine, and 0.2 ml of pyridine were added, and the mixture was stirred at room temperature for 30 minutes. The mixture was concentrated under reduced pressure, diluted with ethyl acetate, and washed with aqueous sodium thiosulfate, aqueous sodium bicarbonate, and aqueous sodium chloride. It was dried over anhydrous magnesium sulfate, filtered, and concentrated. Subjecting human feces to a silica gel chromatography column,
Purification was performed using cyclohexane:ethyl acetate=3:1 to obtain 280 mg (76%) of the target compound.

NMR spectrum (60MHz) (CDC13) δ
ppm0.53-2.78 (58H, m); 3.48
−5.43 (IIH, m [including 5,12 (2H, s)]); 6,25 (IH, d, J=8 Hz); 7.
28-7.48 (101-I, m) Elemental analysis (CsJe
oFNOt t=9I4.206) Carbon Hydrogen Nitrogen Fluorine Theoretical value 68.32 8.82 1.53 2.08 Analysis value 68.17 8.99 1.56 2.131 (
550 mg of the compound obtained in step g) was dissolved in 20 ml of dried tetrahydrofuran and heated to -7 in a nitrogen stream.
At 8°C, 0.4 ml of n-butyllithium (1,6M hexane solution) was slowly added, and 5 ml of a dried tetrahydrofuran solution containing 231 mg of 2-functional dibenzylphosphorochloridate was added dropwise. After 5 minutes, 1 g of 10% palladium on carbon was added at the same temperature and hydrogenated. After 15 minutes, the temperature was returned to room temperature from -78°C and stirred for 3 hours. After filtration, tetrahydrofuran was distilled off under reduced pressure, human feces was applied to a silica gel chromatography column, and chloroform:
Purification was performed using methanol = 5 = 1 to obtain the target compound, 98
The yield was 22.3%.

Mass spectrum NEG, FAB/MS 728 [River-H] - Mika J1 and heart air T ru 2--oxy-2-2'R3'S and 2'S
10 g (38,56 mmo) of the compound obtained in 721(d)
l) in 200 ml of methylene chloride, (±)-
16.06 g of syn-2-fluoro-3-(benzyloxycarbonyloxy)myristic acid was added, and further N
, N'-dicyclohexylcarbodiimide (955 g) was added, and the mixture was stirred at room temperature for 1 hour.

It was filtered, concentrated under reduced pressure, and diluted with ethyl acetate.

The ethyl acetate layer was washed with sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate.

After filtration, the ethyl acetate was distilled off under reduced pressure, and the human feces was applied to a silica gel column and purified with cyclohexane:ethyl acetate = 2 = 1 to obtain the target compound, the N-acyl form (2'R, 3'S
) body and (2'S, 3'R) body, each weighing 9.6 g (3
9.03%) with a yield of 9.67 g (39.31'I).

[(2'R,3'S) compound] NMR spectrum (270MH2) (CDC13) δ
ppm0.88 (3H, t, J=6.9 Hz); 1
．． 18-1.43 (18H, m); 1.47 (3H,
s); 1.53 (3H, s); L, 67-1.98
(2H, m); 3.15-3°24 (IH, m);
3.57-3.84 (5H, m); 3.91 (IH,
d, d, J=5.5°10.6 Hz); 4.02(
LH, d, d, J=6.2, 12.8 Hz); 4.
23-4°30 (LH, m); 4.39 (LH, d,
J=8.06 Hz); 4.94 (LH, d, d.

J=2.2,47.6 Hz); 5.14-5.28
(5H, m); 6.45 (LH, t, J=5.4H
z); 7.34-7.41 (5H, m).

Infrared absorption spectrum vmax (CHCL3) 175
0, 1685.1535 am-1 [(2'S, 3'
R) Compound] NMR spectrum (270MH2) (CDC13) δ
ppm0.88 (3H, t, J=6.9 Hz); 1
．． 18-1.43 (18H, m); 1.45 (3H,
s); 1,53 (3H, s); 1.54-2.01
(2, f(, m); 3.30-3°36 (3B, m)
; 3.55 (IH, t, J=9.5 Hz); 3.
80 (LH, t.

J-10,3Hz); 3.93 (IH, d, d, J=
5.5, 11.0 Hz); 4.01-4.14 (2
H, m); 4.27 (LH, d, d, J = 5.5, 1
8.3 Hz); 4.87 (LH, d, J = 8.4 H
z); 4.91 (IH, d, d, J = 2.2, 48.
0Hz); 5.09-5.3 (5H, m); 5.7
8-5.93 (IH, m); 6.60 (IH, t, J
=5. I H2); 7.26-7.38 (5H,!l
).

Elemental analysis (as CxJszFN09=637.786) Carbon theory value 64.03 Analysis value (2'R, 3'S) 63.96 (2'S, 3'
R) 63.84 Infrared absorption spectrum 1750, 1685.1535 cm-1max Hydrogen Nitrogen &, 22 2.20 8.44 2.59 8.33. 2.76 (CHCb) Fluorine 2.98 2.97 3.02 λ(t)- (2'R, 3'S) compound obtained in 2(a) 3.5
g (5,49mm.

1) was dissolved in 150 ml of methylene chloride, and 1.9
3 g of (R)-3-benzyloxymyristic acid was added, followed by 0.7 g of 4-dimethylaminopyridine, 1
．． 36 g of N.

N'-dicyclohexylcarbodiimide was added and stirred at room temperature for 1 hour. It was filtered, concentrated under reduced pressure, and diluted with ethyl acetate. The ethyl acetate layer was washed with sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate.

After filtration, ethyl acetate was distilled off under reduced pressure, and the human feces was purified with cyclohexane:ethyl acetate = 5 = 1 to obtain the target compound.
．． A yield of 54 g (67.6%) was obtained.

NMR spectrum (270MH2) (CDC13) δ
ppm0.88 (6H, t, J=6.6 Hz); 1
．． 25-1.73 (46H, m); 2.42-2.6
i(2H,nx); 3.35-3.42(IH,m)
,; 3.56-4.08 (6H, m); 4.2i-
4,28 (IH, m); 4.40-4.98 (4H,
m); 5.07-5.36 (6H, m); 5.72
-5.86(H(,m); 6.44-6.48(IH
, m); 7°14-7.35 (10H, m).

Infrared absorption spectrum νmax (CHCL3) 174
3, 1695.1530 cll-12(c) The compound obtained in 46-0-sopropyr-D-glucobylanose 2(b) was treated in the same manner as in 1(g) to obtain the target compound. , with a yield of 2.69 g (79.3%).

NMR spectrum (270MHz) (CDC1B) δ
ppm 0.88 (6H, t, J=6.2 Hz); 1
．． 23-1.73 (46H, m); 2.42-2.5
4 (3H, m); 3.60-4.02 (6H, m);
4.42-5.27 (9H, m); 7,16-7.
46 (IOH, m).

Infrared absorption spectrum vrlax (CHCL3)17
45, 1685.1535 cm-1 3.5 g of (2'S, 3'R) compound obtained in Example 1 Yukai α 3(a)
was treated in the same manner as in Example 2(b) to obtain the target compound 2.
．． Obtained in a yield of 7 g (49°3).

The compound obtained in 2(c) was treated in the same manner as in 1(h) to obtain the target compound in a yield of 91 mg (11%).

Mass spectrum NEG, FAB/S72S728(]-The compound obtained in 3(a) was treated in the same manner as in 1(g),
The desired compound was obtained in a yield of 1.75 g (67.5%).

NMR spectrum (60MHz) (CDC13) δp
pm0.81-2.34 (52H, m); 2.47-2
．． 78 (2H, m); 3.00 (IH, b.

OH); 3.45-5.51 (14H, m[5,12
(4H, s)); 6.65 (LH, b, NH
); 7,35 (IOH, s).

Infrared absorption spectrum vmax (CHCL3) 174
5, 1670. ．． 1545 cm-13(c) The compound obtained in 3(b) was treated in the same manner as in 1(h) to obtain the target compound in a yield of 190 mg (29.3%).

Kenseishin α Luponyloximi “Suyl-46-O-Sopropyl I-
The (2'R,3'S) compound obtained with -D-Glucopyranosa 2(a) was treated in the same manner as in Example 3(a) to obtain 6.1 g (
77.9%) yield.

NMR spectrum (60MHz) (CDC13) δp
pm0.86-2.23 (52H, m); 2.45
-2.84 (2H, m); 3,17-6.30 (1
9H,m [containing 5,12 (4,H,s)); 6.
58 (LH, b, NH); 7°33 (IOH, s).

Infrared absorption spectrum vmax (KBr) 1745,
1671.1545 cm-14 5 g (5.24 mmolj)
was suspended in 50 ml of 80% acetic acid and incubated at 50°C for 3
Stirred for 0 minutes.

Acetic acid was distilled off under reduced pressure. Human feces was applied to a silica gel column and purified using cyclohexane:ethyl acetate=1=1 to obtain the target compound in a yield of 4.55 g (94.8%).

NMR spectrum (270MHz) (CDC13) δ
ppm 0.88 (6H, t, J=6.9 Hz); 1
．． 08-1.84 (40H, m); 2.47 (LH,
d, d, J = 8.1, 15.0 Hz); 2.58 (
IH, d, d, J = 3.7, 15°0 Hz); 3.
26 (IH, b, OH); 3.40-3.45 (LH
, m); 3.61 (IH, t, J=9.2 Hz);
3.75-3.94 (3H, resistance; 4.0O=4.3
1 (2H, m); 4.63 (IH, d, J-8, 4H
z); 4.82-5.28 (IIH, m); 5.7
5-5.88 (LH, nx); 6.00 (LH, d,
d, J=4.4,8°4 Hz); 7.33-7.3
8 (IOH, m).

Elemental analysis (CS 3 H8゜FNO□3=958.21
5) Carbon Hydrogen Nitrogen Fluorine Theoretical value 66.43 8.42 1°46 1.98 Analysis value 66.48 8,72 1,60 1.96 Infrared absorption spectrum vmax (CHCL3) 1745,
4.3 g (4, 5 mmol) in methylene chloride 10
0 ml of 4-dimethylaminopyridine 822
Then, 916 mg of benzyloxychloroformate was added dropwise, and the mixture was stirred at room temperature for 1 hour. It was concentrated under reduced pressure and diluted with ethyl acetate.

The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate.

After filtration, ethyl acetate was distilled off under reduced pressure, and the human feces was purified using a silica gel column with cyclohexane:ethyl acetate=5:1 to obtain 2.43 g (49°6) of the target compound in an unexpected yield. Ta.

NMR spectrum (60MHz) (CDC1a) δ
ppm0.64-1.89 (46H, m); 2.37
-2.64 (2H, m); 3.09-6.20 (22
H,m[5,09(4H,s) ,5.13(2H,s
); 6.49 (LH, b); 7.32 (
15H, s).

Infrared absorption spectrum vmax (CHCL3) 174
5,1695.1533 cm-14(c) was dissolved in 30 ml of methylene chloride, 1.47 g of 4-dimethylaminopyridine was added, and further 1. 62 g of diphenylchlorophosphate was added dropwise and stirred at room temperature for 1 hour. It was concentrated under reduced pressure and diluted with ethyl acetate.

The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate.

After filtration, ethyl acetate was distilled off under reduced pressure, and the human feces was purified using a silica gel column with cyclohexane:ethyl acetate=3:1 to obtain the target compound in a yield of 2.65 g (99.3%). Ta.

NMR spectrum (60MHz) (CDC13) δp
pm0.64-2.05 (46H, m); 2.25-
2.51 (2H, m); 3.00-6.15 (21H
, m[5,08(6H,s) included]); 6,63(
LH, b); 7.18-7.33 (25H, m).

Infrared absorption spectrum νmax (CHCL3) 174
7, 1690.1590.1530 cm-14 mountain α Pyranose The compound obtained in 4(d) was treated in the same manner as in 1(g) to obtain the target compound in a yield of 1.6 g (69.3%). Ta.

NMR spectrum (270MHz) (CD(J3)δ
ppm 0.88 (6H, t, J-6, 2Hz); 1.
13-1.71 (40H, m); 2.37 (LH, d
d, J=7.33.17.22 Hz); 2.55(
IH, dd, J=5.13°17.22 Hz); 3
．． 61 (IH, b); 3,83-3.90 (LH, n
+); 4.16-4.37 (3H, m); 4,64
-4.81 (28, m); 4.96-5.28 (9H
.

a+); 5.56 (IH, dd, J=9.2.11.
0 Hz); 6.84 (IH, dd, J=3.3.7
．． 7 Hz); 7.09-7.37 (25H, m).

Infrared absorption spectrum va+ax (Ct(C13)1
743, 1685.1590 cm - also.

Infrared absorption spectrum νmax (KBr) 1710,
1660 cm-1 Mass spectrum NEC, FAB/MS M/2728 (MH)-1.3 g (1,01 cm) of the compound obtained with 4(e)
) was dissolved in 30 ml of tetrahydrofuran, 1 g of 10% palladium on carbon was added, and catalytic reduction was carried out at room temperature for 3 hours. After filtration, 200 rag of platinum oxide was added to the filtrate, and catalytic reduction was performed again at room temperature for 2 hours. After filtration and distilling off tetrahydrofuran under reduced pressure, the human feces was applied to a silica gel column and purified using chloroform:methanol=9:1 and then chloroform:methanol=5:1 to obtain 490 mg (66.3%) of the target compound. 4.5 g of the (2S,3R) compound obtained with heart α2(a)
7,06 mmol), 100 m of tetrahydrofuran
857 ml of triethylamine was added thereto, and further 2.86 g of 3-benzyloxymyristic acid chloride was added dropwise, followed by stirring at room temperature for 1 hour. The ethyl hexaacetate layer, which was concentrated under reduced pressure and diluted with ethyl acetate, was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. Filter and remove ethyl acetate under reduced pressure.
Human feces was applied to a silica gel column and purified with cyclohexane:ethyl acetate=5:1 to obtain 5.1 g of the target compound (
75.7%) yield.

NMR spectrum (60MHz) (CDC13) δp
pm0.65-2.08(52H, m[1,43(3H
, s)]); 2.43-2.72 (2H, m)
; 3.05-6.21(19H, m[4,48(2H
, s); 5. l2 (2H.

S)]); 6.31-6.67 (IH, m);
7.28 (5H, s); 7.30 (5H, s).

Infrared absorption spectrum νmax (KBr) 1745,
1670.1545.1268.1089 cm-15
(b) The compound obtained in 5(a) was treated in the same manner as in 4(b) to obtain the desired compound in a yield of 4.14 g (96%).

NMR spectrum (60MHz) (CDC13) δp
pm0.62-2.18 (46H, m); 2.32-
2.91 (4H, m); 3.20-4.25 (8H,
! l); 4.28-4.71 (3H, m[4,48,
(2H, s)); 4.86-6.19 (8H,
m); 6.45-6.85 (IH, m); 7,28
(5H, s); 7.31 (5H, s).

Infrared absorption spectrum νwax (KBr) 1742,
1669.1578.1271 C! l-1danfuσ through 4-0-diphenoxyphosphinyl-6-0
The compound obtained in 5(b) was treated in the same manner as in 4(c) to obtain the target compound in a yield of 2.85 g (65.4%).

NMR spectrum (60MHz) (CDCh) δpp
m0.85-2.08 (46H, m); 2.41-2
．． 64 (2H, m); 3.00 (IH, b); 3.
48-6.08(21H,m[4,45(2H,s),
5.15(4H,s)); 6.18-6.7
2 (IH, m); 7.26-7.56 (15H, m)
.

Infrared absorption spectrum νmax (KBr) 1750,
The compound obtained with 1727.1676, 1548 cm-15(c) was treated in the same manner as in 4(d) to obtain the target compound in a yield of 3.16 g (99.5%).

NMR spectrum (60MH2) (CDC13) δp
pm0.72-1.87 (46H, m); 2.26-
2.49 (2H, m); 3.45-6.05 (21H
, m[4,30(2H,s) ,5.05(4H,s)
); 6.18-6°50 (IH, m); 6
．． 89-7.49 (25H, m).

Infrared absorption spectrum 乍wax (KBr) 1743,
1679.1541.1494 am-1 Ruamide-3
The compound obtained in -0-3'R-3'-benzyloximi 15(d) was treated in the same manner as in 1(g) to obtain the target compound in a yield of 1.8 g (66.4%). Obtained.

NMR spectrum (60MH2) (CDC13) δp
pm0.66-2.01 (46H, m); 2.161
6-2-56 (2Ht; 2.89 (iLd.

J: 5 Hz); 3.38-5.71 (16H, m[
432 (2H, s), 5.10 (4H, s)])
; 6.45-6.81 (lti, m); 7.08-
7.45 (?5H, m).

Infrared absorption spectrum vmax (KBr) 1747,
1685.1590 cm+-1 Carbon Hydrogen Nitrogen Fluorine Phosphorus Theoretical value 62.64 8,34 1,59 2,15
3.51 Analysis value 62.89 8.24 1.47 2
．． 15 880 mg of the compound obtained in 3.415(e) (
0,6111101) was dissolved in 30 ml of tetrahydrofuran, 1 g of 10% palladium on carbon was added, and catalytic reduction was carried out at room temperature for 2 hours. After filtration, tetrahydrofuran was distilled off under reduced pressure, and the human feces was applied to a silica gel column and purified with ethyl acetate to obtain 340 mg of the target compound.
6 Elemental analysis (C46H?aFN (hzP=882.057) obtained with a yield of (56,2%)
) 490 mg of the compound obtained in 5(f) (0,56
mmol) was dissolved in 30 ml of tetrahydrofuran, 80 mg of platinum oxide was added, and catalytic reduction was performed at room temperature for 3 hours. After filtration, tetrahydrofuran was distilled off under reduced pressure to obtain 380 mg (93.7 mg) of the desired compound in an unexpected yield.

Elemental analysis (C34HG 5FNotsu2P”729.86
1) Carbon Hydrogen Nitrogen Fluorine Phosphorus Theoretical value 55,95 8.98 ・1.92 2゜6
0 4゜24 analysis value 55.84 9.22 1゜94
2.51 4.09 Mass Spectrum NFC, FAB/MS M/2728 (MH) - 502° Implementation 5.18 g (20 mmol) of the compound obtained in 1(d) was added to 150 ml of methylene chloride. Dissolve and add 9.93 g (
±)-syn-2-fluoro-3-myristoyl ogicimyristonic acid was added thereto, followed by 4.95 g of N,N'-dicyclohexylcarbodiimide, and the mixture was stirred at room temperature for 1 hour.

Filtered, concentrated under reduced pressure and diluted with ethyl acetate.

The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate.

Ethyl acetate was distilled off under reduced pressure, human feces was subjected to silica gel chromatography, and purified with cyclohexane:ethyl acetate = 3 = 1 to obtain the target compound, the N-acyl form, (2'R, 3'S
) body and (2'S, 3'R) body each 5.65 g
(3986%) with a yield of 5.55 g (38.9%).

NMR spectrum (270MH2) (CDC13) δ
ppln[(2'R,3'S) compound] 0.88 (6H, t, J = 6.9 Hz); 1.20
-1.38 (38H, m); 1.44 (3H, s);
1.52 (3H, s); 1.60-1.84 (5H
, n+); 2.30 (2H.

t); 3,23-3.33 (LH, n+); 3.5
8-3.85 (48, m); 3.93 (1) 1. d,
d, J = 5.5, 10.6 Hz); 4.07 (LH
, d, d, J=6.2, 12j3Hz); 4.30-
4.37 (IH, m); 4.76 (IH, d J=7
．． 7Hz); 4°93 (IH, d, d, J=2.9,
48.0 Hz); 5.20-5.36 (3H, m)
; 5°79-5. '94 (IH, m); 6.44 (
IH, t, J = 5.5 Hz).

Infrared absorption spectrum vmax (CHCh) I735
．． 1680.1535 cm-1 [(2'S, 3'R)
Compound] 0.88 (6H, t, J=6.9 Hz); 1.20
-J,, 38 (38H, m); 1.45 (3H, s)
; 1.52 (3H, s); 1.56-1.76 (5
H, ff1); 2.29 (2H.

t); 3,30-3.41 (2H, to); 3.5
7 (IH, t, J = 9.2 Hz); 3°80 (LH
, t, J=10.6 Hz); 3.93 (IH, d,
d, J=5.5, 11.0 Hz); 4.05-4.
16 (2H, nu); 4.29-4.36 (IH, m
); 4.77 (LH, d, J=8.1 Hz); 4
．． 89 (1, H, d, d, J = 2.2, 48.0 Hz
); 5°20-5.34 (3H, m); 5.80-
5.89 (IH, m); 6.52 (IH, t, J=5
．． 5 Hz).

Infrared absorption spectrum 1-vmax (CHCL3)17
35, 1680.1535 am-1 Dankarasu y Compound (2'R23'S) compound obtained in 6(a) 2 g
(2.8 mmol) was dissolved in 3011 methylene chloride, 728 mg of myristic acid chloride was added, and then
31.3 mg of triethylamine was added, and the mixture was stirred at room temperature for 1 hour. It was concentrated, diluted with ethyl acetate, washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration and distilling off ethyl acetate under reduced pressure, the human excrement was applied to a silica gel column and purified using cyclohexane:ethyl acetate=5=1 to obtain 1.35 g (5
2.1%) yield.

NMR spectrum (270MH2) (CDC13)
δppm0.88 (9H, t, J=6.6 Hz);
1.13-1.67(70H,Xn[1,36(3H
.

s), 1.46 (3H, s)]); 2.25-2
．． 35 (4H, m); 3.32-3.41 (LH, n
+); 3.66-3.85 (3H, m); 3.95
(IH, d, d, J=5.5, 10.6 Hz); 4
．． 05 (LH, d, d, J=6.2, 12.8 Hz)
; 4°26-4.34 (iH, m); 4.74-4
．． 93 (2H, m); 5.16-5.29 (4H.

m); 5.75-5.89 (LH, m); 6.34
(LH, d, d, J = 4.4, 8.8 Hz).

Elemental analysis (as C54H98FN09 = 924.374) Carbon Hydrogen Nitrogen Fluorine Theoretical value 70.17 10.69 1.52 2.06
Analysis value 70.41 10.58 1.47 1.99
Infrared absorption spectrum vmax (CHC, L3) 17
4.0.1695 CD! -1 Mass spectrum M/Z 924 (M"+1), 909.883.86
7, 737.724°655, 638.610.526
．． 5L3.452゜d α r 2--Oshi 2- 2'R, 3'S -2
'-Flow 3'-Mirsoxime The compound obtained in Surami-3-6(a) was treated in the same manner as in 4(b) to obtain 2 g (80,4 %)
yield was obtained.

NMR spectrum (60MHz) (CDC13) δp
pm0.66-1.91. (74H, m); 2.09
-2.55 (4H, m); 2.87-6.16 (15
H, m); 6.54 (IH, n+).

Infrared absorption spectrum vmax (KBr) 1739,
1668.1553.1468.1175 cm-1
1.9 g of the compound obtained in step 6(c) (2,15 o1
) was dissolved in 20 tml of methylene chloride, and 550 m
Add 3 g of benzyloxychloroformate and add 3 g of benzyloxychloroformate.
27 mg of triethylamine was added and stirred at room temperature for 5 hours. It was concentrated and diluted with ethyl acetate. The ethyl acetate layer was washed with sodium bicarbonate water and brine,
It was dried with anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the human feces was applied to a silica gel column and purified using cyclohexane:ethyl acetate=3:1 to obtain the target compound in a yield of 660 mg (30.2%). Ta.

NMR spectrum (270MH2) (CDC13) δ
ppm0.88 (9H, t, J=6.9 Hz); 1
．． 25-1.65 (66H, m); 2.25-2.3
6 (4H, m); 2.82 (IH, s); 3.59
-3.66 (2H, m); 4.03 (IH, d, d,
J = 6.2, 12.8 Hz); 4.27 (IH, d
, d, J=5.1, 12.8 Hz); 4.42-4
．． 52 (IH, m); 4.81 (IH, d, d, J=
3.7°47.6 Hz); 4.84 (LH, d, J
-8,1Hz); 5.14-5°27 (61(.

m); 5.76-5.89 (1) 1. ! l); 6.
37 (LH, d, d, J = 4.4, 8.1 Hz); 7
．． 34-7.40 (5H, m).

Infrared absorption spectrum vmax (KBr) 1737,
1673.1550.1285 c, r-13'-mi1
Stoyloxymyristoylamido-3--myrs
Sea 4-0-? 600 mg (0,589 mmol) of the compound obtained in 6(d) was dissolved in 20 ml of methylene chloride, 474.8 mg of diphenyl chlorophosphate was added, and further 62.6 mg of triethylamine was added. was added and stirred at room temperature overnight.

It was concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the human feces was applied to a silica gel column and purified using cyclohexane:ethyl acetate=5=1 to obtain the target compound in a yield of 600 mg (81,6).

NMR spectrum (270MHz) (CDCI 3)
δppm0.88 (9H, t, J=6.9 Hz);
1.05-1.73 (64H, m); 2.11-2
．． 3 (4H, m); 3.46-3.56 (IH, m)
; 3.77-3.82 (IH, m); 4.03 (IH
, d, d, J=6.2, 12.8 Hz); 4.19
-4.38 (3H, m); 4.63-4.89 (2H
, m); 5,01-5.26 (6H, m); 5.6
4-5.87 (2H, m); 6.37 (LH, d, d
, J=4.4,7.7 Hz); 7.11-7.34
(15H, m).

Elemental analysis (C71H109FN014P=1250.6
18) Carbon Hydrogen Nitrogen Fluorine Phosphorus Theoretical value 68.19 8.79 1.12 1.52
2.48 Analysis value 67.97 8,56 1,21 1
,47 2.47 Infrared absorption spectrum νmax (C
HCL3)L743.1690 cm-1 6(f) The compound obtained in 6(e) was treated in the same manner as in 1(g) to obtain the target compound in a yield of 490 mg (84.3%').

NMR spectrum (270MHz) (CDC13) δ
ppm0.88 (9H, t, J=7.0 Hz); 1
．． 11-1.66 (64H, m); 2.11-2.2
9 (4H, r++); 3.36 (IH, s); 4.
13-4.39 (4H, nx); 4.71-5.56
(7H, El); 6.70 (IH, d, d, J=3.
3,8.1 Hz); 7.11-7.35 (15H,
m).

Infrared absorption spectrum νmas (CHCL3) 1751
, 1711.1658 cm-16(f) was treated in the same manner as 5(f) to obtain the target compound at 270 cm.
The yield was 75.9%.

Elemental analysis ((r, oH9sFNOt2P=1076.4
19) Carbon Hydrogen Nitrogen Fluorine Phosphorus Theoretical value 66.95 9.27 1.30 1.76
2.88 Analysis value 67.23 9.27 1.35 1
．． 91 2.81 Infrared absorption spectrum νwax (C
HCL3) 1735, 1685 cm-1 "-3-0-" r
The compound obtained with su-D-glucopinosyl-4-phosphate 6(g) was treated in the same manner as 5(g) to obtain the target compound in a yield of 190 mg (96.2%).

Mass spectrum NEC, FAB/MS M/Z 922 (M-l- Example 7 - 2.9 g of (2'S, 3'R) body obtained at °Cσ 6(a)
4,06 mmol) was dissolved in 30 ml of methylene chloride, 1.02 g of myristic acid was added, and 1 g of N,N'-dicyclohexylcarbodiimide was added, and the mixture was stirred at room temperature in the dark for 1 hour, but the reaction did not proceed. Therefore, 4 more
-Add 50 mg of dimethylaminopyridine and add 1 at room temperature.
Stir for hours. It was concentrated under reduced pressure, diluted with ethyl acetate, and the ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the human feces was applied to a silica gel column.
Purification was performed using cyclohexane:ethyl acetate=5:1 to quantitatively obtain the target compound.

NMR spectrum (60MHz) (CDC13) δp
pm0.66-2.01 (79H, m); 2.05-
2.61 (4H, m); 3.30-6.23 (14H
, m); 6.85 (IH, m).

Infrared absorption spectrum vmax (KBr) 1741,
1666, 1544.1468 cm-17(b) The compound obtained in 7(a) was treated in the same manner as in 4(b),
The desired compound was obtained in a yield of 3.08. (84.7%).

Infrared absorption spectrum vyrax (KBr) 1736
, 1671.1553.1467 cm-11 σ 7(b) 2.7 g (3,05n+m
ol) was dissolved in 50 ml of methylene chloride, 0.525 g of benzyl chloromethyl ether was added, and further 0.355 g of tetramethylurea was added, and the mixture was heated under reflux for 6 hours. Methylene chloride was distilled off under reduced pressure, and the human feces was applied to a silica gel column and purified with cyclohexane:ethyl acetate=3:1 to obtain the target compound in a yield of 2.08 g (67.8%).

NMR spectrum (270MHz) (CDC13) δ
ppm0.88 (9H, t, J=6.9 Hz); 1
．． 20-1.73 (65H, a+); 2.24-2.
37 (4H, IEI); 3.47-3.51 (IH,
Resistance: 3.74 (IH, t, J=9.5Hz); 3.
89-4.11 (4H, n+); 4.26-4.33
(IH, m); 4.59 (IH, d, J=8.4 H
z); 4.63 (21-1, s); 4.79 (LH
, d, d, J=4°3.48.4 Hz); 4.81
(2H, s); 5,03 (LH, d, d, J=9.2
, 10°6 Hz); 5.15-5.30 (3H, m
); 5.80-5.88 (LH, m); 6.36 (
IH, d, d, J = 4.4, 9.2 Hz); 7.2
9-7.36 (5H, n+).

Infrared absorption spectrum vmax (CHCL3) 343
0, 1738.1695 cm-1 Mass spectrum M/2986.928.834.775.717.59
6.509°456, 383.354.298.285
．． 268°7(d) 38(IH, d, J=4.8,9.2 f(z); 7
．． 13-7.44 (15H, m).

Infrared absorption spectrum vmax (CHCla) 343
0, 1740.1695 cm-1 Mass spectrum M/Z 1014.994.758.670.580.
440.322°268° The compound obtained in lanocide 7(c) was treated in the same manner as in 6(e).

The target compound was obtained quantitatively.

NMR spectrum (270MHz) (CDCb) δp
pm0.88 (9H, t, J=6.9 Hz); 1.
10-1.68 (65H, m); 2.08-2.31
(3H, n+); 3.65-3.69 (2H, m);
3.78-3.84 (IH, m); 4.03-4.
11 (2H, m); 4.25-4.32 (IH, m)
; 4.50-4.85 (7H, I); 5.15-5
．． 39 (4H,!+1); 5.76-5.83 (IH
, El); The compound obtained in 6°7(d) was treated in the same manner as in 1(g) to obtain the target compound in a yield of 1.58 g (71%).

NMR spectrum (60MH2) (CDC13) δp
pm0.63-2.42 (77H, m); 3.55-
5.78(14H,n+[4,54(ZH,s).

4.66 (2H, s)); 6.70 (IH,
m); 7.00-7.53 (15H, m).

7(f) 2-""'oxy2-2'S 3'R-2'-F
Follow 3'-mi1st Ruoximi τ stylamide-
3-0-mi ■ Compound i obtained in 17(e), 44 g
(1.2 mmol) was dissolved in 30 ml of methanol, 1 g of 10% palladium carbon was added, and catalytic reduction was carried out at 40 to 45°C for 3 hours.

After filtration, methanol was distilled off under reduced pressure, and the human feces was applied to a silica gel column and purified using cyclohexane:ethyl acetate=1:1 to obtain the target compound in a yield of 715 mg (55.2%).

Infrared absorption spectrum νwax (CHCL3)344
0, 1740.1690 cn+-1 elemental analysis (CG
. As Hg5FN012P=1076.419) Carbon Hydrogen Nitrogen Fluorine Phosphorus Theoretical value 66.95 9.27 1.30 1.76
2.88 Analysis value 66.96 9.30 1.17 1
．． 74 2.81 J force σ 2--oC2-2'S 3'R-2'-Follow 3/-Q+mu The compound obtained in 7(f) was treated in the same manner as in 5(g). , the target compound was obtained in a yield of 420 mg (89%).

Mass spectrum NEC, FAB/MS M/Z 922 (and -H) - Dilute the Ωα side with 300 ml of ethyl acetate, add 15 to 20
The mixture was neutralized by adding 3 g of acetic acid IO at °C. Next, the mixture was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 30 g of the title compound as an oil. This product was subjected to silica gel column chromatography (cyclohexane: ethyl acetate = 9:
Although it could be purified by 1), it was used as it was in the next deprotection reaction.

8(b) Allyl 2-trifluoroacetamide-α-D-glucopyranoside ia g, (±)-3 obtained in 1(c)
-benzyloxy-1-mesyloxydecane 16.5
g was dissolved in 110 nil of dry dimethylformamide, and 7.5 g of 55% sodium hydride was added little by little under water cooling, followed by stirring at room temperature for 3 hours. Reaction liquid: α-D-glucopyranoside 7■15 30 g of the 2-trifluoroacetylamino compound obtained in 8(a) was dissolved in 550 ml of ethanol, and 275 ml of 1N aqueous sodium hydroxide solution was added to this. was added, and the mixture was stirred and refluxed for 2 hours. The reaction solution was concentrated and diluted with 700 ml of ethyl acetate, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. Next, it was concentrated to dryness and purified through a silica gel column (cyclohexane: ethyl acetate = 3:2) with a volume 30 times that of human excrement, resulting in the title compound 12.3.
g was obtained as an oil.

NMR spectrum (CDC13): δppm0.7
-2.1 (23H, ++); 2.5-2.9 (LH,
m); 3.0-4.2 (IOH, m); 4.5 (2
H, s); 4.7-6.3 (4H, m); 7.3 (
5t(,s).

12.3 g of the 2-amino compound obtained with Al 2--oxy-2-3'S-3'-benzyloximi-T sulami 3"R3-3'-ben8(b), (
±) 9.8 g of -3-benzyloxymyristine fi was dissolved in 150 ml of dry methylene chloride, and 6.0 g of N,N'-dicyclohexylcarbodiimide was added to the solution at room temperature.
5 g was added and stirred at room temperature for 2 hours. The reaction solution was filtered to remove precipitates, and then methylene chloride was distilled off under reduced pressure. Next, a chromatography column (cyclohexane: ethyl acetate = 4
: When purified through 1), the title (R) compound 7.5
g, 7.8 g of (S) compound was obtained.

[(R) Compound] NMR spectrum (CDC13): δppm0.7
0-2.05 (46H, m); 2.2-2.5 (2H
, m); 3.2-6.6 (26H.

m); 7,3 (IOH, -s).

Infrared absorption spectrum ν,,, am-1 (CHCL3
); 1662° mass spectrum (m/e): 822 (M”+1), 806.730.672.6
09.568.516° [(S) compound] Infrared absorption spectrum ν,,, cm(, (CHCb)
; 1661 Mass spectrum (m/e): 822
(M”+1).

(R)-2-acyl compound obtained in 8(c) 3.7&
was dissolved in 170 ml of dry tetrahydrofuran, and 0.26 g of iridium complex (1,5-cyclooctadiene-bis[methyldiphenylphosphine coiridium hexafluorophosphate) was added thereto. The air in the reaction vessel was sucked out with an aspirator and replaced with nitrogen. Next, the nitrogen was suctioned with an aspirator, hydrogen was added thereto, and the mixture was stirred for 5 minutes to activate the iridium complex. Next, hydrogen was removed in the same manner, the mixture was replaced with nitrogen, and the mixture was stirred at room temperature for 3 hours. Add 7 ml of water and 2.3 ml of iodine to the reaction solution.
After adding 1.4 g of pyridine and stirring at room temperature for 15 minutes, tetrahydrofuran was evaporated under reduced pressure. Human feces was diluted with ethyl acetate, washed with 5% aqueous sodium sulfite solution, saturated aqueous sodium bicarbonate solution, and saturated saline in this order, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, human feces was purified by 50 times the amount of silica gel column chromatography (cyclohexane:
Ethyl acetate = 7: 3) Then the title compound oil 3
．． 2g was obtained.

NMR spectrum (CDC13): δppm0.7
-1.9 (46H, m); 2.2-2.55 (2H,
m); 3.0-4.0 (IIH.

nt); 4.45-4.55 (4H, m); 5.0
-5.15 (LH, m); 6.4 (iH.

d, J=8.5 Hz); 7.34 (IOH, s).

Infrared absorption spectrum ν76, cm-1 (liquid film): 33
00, 1735.1641.1652° Mass spectrum (m/e): 609, 551.519.502.488.417° -α-D-glucopyranosyl-1-phosphate-8 (d
) (1.17g, 1.5 mmol)
A solution of 20ml of dry tetrahydrofuran was added under a nitrogen stream.
While cooling to 78°C and stirring, add 1 of n-butyllithium.
．． 6M hexane solution 1.02 ml (1.65 mmol
) was added and 2 minutes later, dibenzylphosfluorochloridate [CIP (0) (OBn) 2,580 mg, 1.
95 mmol, 1.3 equivalents] of tetrahydrofuran 1
0 ml solution was added. After stirring at −78° C. for 10 minutes, 4.0 g of 10% palladium on carbon was added, and the mixture was heated at −60° C. for 30 minutes in a hydrogen stream, and then the cooling bath was removed and the mixture was reduced at room temperature for 3 hours. Palladium on carbon was removed by filtration, washed with methanol, and the solution was concentrated. Next, silica gel column chromatography was performed.

This elementary reactant remains coated with acetonide, but
Acetonide is removed by silica gel force chromatography. Chloroform-methanol (1:1)
All the eluates were collected and then rechromatographed on a 30 g silica gel column. Elution was performed with a 1% methanol solution in chloroform to obtain 402 n+g (41,7X) of the desired product.

NMR spectrum (CD3COOD): 270M
Hz 8 ppm0.90 (6H, m); 1.14-
1.83 (34H, m); 2.54 (2H, m);
3°45-4.40 (IOH, m); 5.76 (IH
, ns).

FAB7 Spect/L/ (M/Z): 640
[M-Old-.

Remove loloform under reduced pressure and remove 0. Triethylamine was dissolved in water, and this aqueous solution was used as a sample for activity measurement.

Example 9 Ωα If it is necessary to obtain the water-soluble triethylamine salt of the phosphoric acid compound obtained in 8(e), the following operation is performed.

Suspend 30 mg of phosphoric acid in 8 ml of 0.1 N hydrochloric acid, and then add 30 mg of chloroform-methanol (1:2).
ml was added and dissolved by applying ultrasound. When 10 ml of chloroform and 10 ml of 0.1N hydrochloric acid were added to this solution, it separated into two layers, and the chloroform layer was separated.

(S)-2-acyl compound obtained in 8(c) 1.7
g was treated in the same manner as in Example 8(d) to obtain 1.5 g (92%) of the title compound as an oil.

NMR spectrum (CDC13): δ ppm0.
7-1.9 (46H, m); 2.3-2.55 (2H
, Em); 3.3-4.1 (IOH.

m); 4.44 (2H, S); 4.50 (2H, S
); 5.1-5.3 (IH, m); 6°6 (IH,
d, J=8.5 Hz); 7.32 (108, s).

Infrared absorption spectrum νreaX cm-1 (liquid film);
3310, 1740 (W), 1648.1655 (s
h).

Treated as in Example 8(e), 247 mg (25,
7%) of the desired product was obtained.

NMR spectrum (CD3GOOD): 60MH
zδppm0.7-1.0 (6H, m); 1.0-L
, 5(34H,n+); 2-2-4-2-8(2Hy
; 3.4-4.4 (IOH, m); 5.64 (IH
, m).

FAB? X Spect)'v (1'l/Z): 64
0 [M-Hl-.

Example 10 Compound obtained in 9(a) (1.17 g, 1.5 m
33.1 g of the (2'S, 3'R) compound obtained in 2(a) was dissolved in 700 ml of methylene chloride, 25.9 g of 3-myristoyloxymyristic acid was added, and an additional 7 g 4-dimethylaminopyridine, 1
2.8 g of N,N'-dicyclohexylcarbodiimide was added and stirred at room temperature for 2 hours. After filtration, it was concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography and purified using cyclohexane:ethyl acetate=5:1 to obtain the target compound at 47%
．． A yield of 7 g (85.5%) was obtained.

NMR spectrum (CDCIJ): δ ppm0.
'86-0.90 (9H, m); 1.25-1.77
[68H,m, [1,37(3H,S); 1.48(
2.26 (2H, m); 2
．． 49 (1, H, dd.

J = 6.3, 15.1 Hz); 2.62 (IH, d
d, J = 6.3, 15.1 Hz); 3.70-3.8
6 (5H, na); 3-3-93-3-98 (IHy
; 4.21-4.27 (IH, m); 4.63 (I
H, d, J = 3.9 Hz); 4.90 (IH, dd
, J=2.4,47.4 f(z); 5.09-5.
21. (7H, m); 5.74-5.84 (IH.

[0); 6.63 (IH, dd, J=3.9, 9.8
7.26-7.36 (5H, m) Infrared absorption spectrum νn+ax cm 1 (CHCL3);
3440, 1745.1690.1530゜Elemental analysis:
Calculated value as C62H104NFO12: C:69
．． 30. H: 9.76, N: 1.30. F:1.
77° Actual value: C: 69.39. H:9.86.
N: 1.31. F: 1.75°10(b) 4.6 g of the compound obtained in 10(a) was treated in the same manner as in 4(b) to obtain the target compound in a yield of 4.2 g (94.8%). Obtained.

NMR spectrum (CDCb): δppm0.85
-0.90 (9H, m); 1.04-1.78 (6
4H, m); 2.26-2.31 (2H, m);
2.47-2.59 (2f(,m); 3.63-
3.88 (5H, m); 3.96-4.02 (IH,
o+); 4.16-4.23 (IH, m); 4.6
6 (LH, d.

J=3.7 Hz); 4.89(IH, dd, J=2
．． 2,47.6 Hz); 5.09-5.21 (7H
, ni); 5.73-5.87 (IH, m), 6.
66 (IH, dd, J=3.7, 9.5 Hz); 7
．． 26-7.37 (5H, ta).

Infrared absorption spectrum y,, IXcm-], (KBr
); 1741, 1719.1703.1670.154
5.1468゜Elemental analysis: C59H100NFO12
Calculated value: C: 68.51. H:9.74.
N: 1.35. F: 1.84° Actual value: C: 68.
62. H:9.70. N: 1.55. F:1.8
0°10(c) Calculated value: C: 6g, 86. )(:9.14.N:
1.20. F: 1.63° Actual value: C: 68.77
, H:9.1&, N:1.42. F: 1.64°10(d) 23.1 g of the compound obtained in 10(d) was treated in the same manner as in 4(c) to obtain 10.6 g (40.6%) of the target compound.
) was obtained with a yield of

NMR spectrum (CDC13): δppm0,8
5-0.90 (9H, n+); 1,02-1.77 (
62H, ax); 2.25-2.31 (2H, m);
2.46-2.59 (2H, m); 3.31 (IH
, d, J=4.2 Hz); 3.61 (IH, td,
J = 9.3, 4.2 Hz); 3.76-3.86 (
2H, m); 3.93-4.00 (IH, m); 4.
16-4.24 (LH, m); 4.38-4.48 (
IH, m); 4.88 (ltl, dd, J=2.2,
47.6 Hz); 5.07-5.19 (9H, ng
); 5.70-5.85 (LH, m); 6.62 (
IH, dd, J=3.7°9.5 Hz); 7.26
-7.40 (IOH, tl).

Infrared absorption spectrum v r-aw cflll (
KBr) ;1747, 1738.1724.1712
．． 1678.1547゜Elemental analysis: C67H106N
Compound 10.47 obtained in 10(c) as FO14
g was treated in the same manner as in 4(d), and the target compound was obtained in 11.
Obtained with a yield of 46 g (91.3%).

NMR spectrum (CDC13): δppm0,8
5-0.90 (9H, m); 1.03-1.80 (6
2H, ra); 2.13-2.19 (2H, m);
2.33 (LH, dd, J=7.3, 15.8 Hz)
; 2.42 (LH.

dd, J=5.1, 15.8 Hz); 3.75-3
．． 82 (If (, m); 3.89-4.02 (2H,
Dl); 4.17-4.36 (3H, El); 4.
64 (IH, d, , J = 3.7Hz); 4.72 (I
H, dd, J-9,2,18,7Hz); 4.85-
5.22 (9H, m); 5.42 (LH, dd, J=
9.2, 11. OHz); 5.70-5.84(1)
f, m); 6.56 (IH, dd, J=3.7, 9.
5 Hz); 7.12-7.65 (20H, m).

Infrared absorption spectrum νnhx am-1 (film)
;1750, 1690.1590゜Elemental analysis: CHN as C79H115NFO17P
F P calculated value: 67.74.8.28.1,00.1.3
6.2.21° Actual value: 68.77, 9.18.1
．． 42.1.64.2.14゜lo(e) (2H,!II); 2.32(IH, dd, J=7.
3,15.8 Hz); 2.41 (IH.

dd, J = 5.5, 15.8 Hz); 2.70 (I
H, dd, J = 1.5, 4.8 Hz); 4.09-4
．． 18 (3fLm); 4.29-4.34 (IH, m
); 4.67 (IH.

dd, J-9,2,18,7Hz); 4.87(LH
, m); 4.89 (IH, dd, J = 1.8, 47.
3 Hz); 5.61-5.25 (6H, m); 5
．． 46 (LH, dd, J = 9.2, 11゜OHz);
6.63 (IH, dd, J=3.3, 8.8 Hz);
7.12-7.38 (20H, o+).

Infrared absorption spectrum νr+15LX cm-1 (KB
r); 1739, 1660.1290.1266, 12
50.1195゜Elemental analysis: C76H111FNO1
HNFP as 7P Calculated value: 67.09.8.22.1.03.1.40
．． 2.28°Actual measurement: 67.04.7.97.1.6
4.1.35.2.15゜1.4g of the compound obtained in 10(d) was treated in the same manner as in ■(g) to obtain 0 of the target compound.
．． A yield of 77 g (56,6'1) was obtained.

NMR spectrum (CDC13): δppm0.8
5-0.90 (9H, m); 1.18-1.82 (6
2H, m); 6.5 g of the compound obtained in 2.12-2.1810 (e) was treated in the same manner as in 5 (f), yielding 4.89 g (93.7%) of the target compound. I got it.

NMR spectrum (CDC13): δppm0.8
5-0.90 (9H, rM); 1.18-1.80 (
62H, m); 2.13-2.21 (2H, m);
2.37-2.39 (2H, m); 3.50-3.6
1 (4H, m); 3.97-4.06 (2H, m);
4.21-4.28 (IH, m); 4.65-4.83
(2H, m); 5.04-5.13 (IH, m);
5.24-5.28 (2H, m); 5.49-5.57
(IH, m); 6.80-6.85 (IH, m);
7.14-7.38 (10t(,m).

Infrared absorption spectrum vr, ax cn>-1 (KBr
);1.735.1671.1289.1202.10
60° elemental analysis: H as C60H99FNO13P
NFP calculated value: 65.97.9.13.1.28.1.74
．． 2.84°Actual measurement value: 65.93.9.25.1.4
8.1.63.2.84° Ristoyloxymyristoyl-D-glucopyranosyl-4-phosphate 4.59 g of the compound obtained in 10(f) was added to 5(g)
3.9 g (98.7%) of the target compound
) was obtained with a yield of

NMR spectrum 270MHz δppm (heavy pyridine) 0.85-0.90 (9H, m), 1.03
~2.15 (62H, m), 2.43~2.49 (2
H, m), 3.08-3.25 (2H, m), 4.
09-4.13 (IH, m), 4.52-4.56 (
2H, m), 4.62-4.65 (IH, m).

4.99-5.08 (LH, m), 5.21-5.4
9 (2H, m), 5.63-5.74 (2H, m),
6.24-6.31 (IH, m), 8.03-8.
72 (6H, m) Infrared absorption spectrum y,, aXam-1 (KBr);
1734, 1661.1550.1465.1224.
1182.1171゜1063゜Elemental analysis: CI-I as C48H91FNO13P
NFP calculated value: 61.32.9.76, 1.49.2.02
．． 3.29° Actual value: 60.66, 9.87.1.6
8.1.91.3.10゜Example 11 1.1 g of (2'R, 3's) compound obtained in heart α 2(a)
was treated in the same manner as in 10(,) to obtain the target compound at 1.3
Obtained in a yield of 6 g (73, Seki).

Infrared absorption spectrum C,,,xcnt-1 (film); 1740, 1685.1530.1460° Elemental analysis: C62H104FNO12 calculated value: C: 69
,30. H: 9.76, N: 1.30. F:1.
77° Actual value: C: 68.94. H:9.58.
N: 1.26. F: 1.76゜Stain J Through α-
D-glucopyranocyst.

57.6 g of the compound obtained in 11(a) was added to 4(b)
42.6 g (76°8
I got it with a fantastic yield.

NMR spectrum (CDC13): δppm.

0.86-0.90 (9H, (1); 1.25-1.
76 (64H,!II); 2.25-2.45 (4H
, m), 3.64-3.76 (3H, m), 3.8
5-3.90 (ZH, m); 3.95-4.00 (IH
, m); 4.14-4.21 (2H, m); 4.8
4-5.32 (8H, m); 5.83-5.87 (I
H, m); 7.07-7.10 (IH, m); 7.2
6-7.38 (5H, durable.

Elemental analysis: C59H100012NF calculated value: C:
68.51. H:9.74. N: 1.35. F:
1.84° Actual value: C: 68.27. H:9.97
．． N: 1.48. F: 1.92゜amy3-0-3'R-3'-miTsulfokyl-α-D-glucopyranoside 11 (b) 0.83 g of the compound obtained in 4 (c
), and 0.6 g (63,6
%) yield.

NMR spectrum (CDC13): δppm0.8
6-0.90 (9H, tm); 1.25-1.76 (
63H, m); 2.23-2.45 (4H, m);
3.63-3.65 (2H, n+); 3.85-3.
98 (2H, m); 4.11-4.19 (2H, m);
4.43-4.93 (2H, [1); 4.89 (I
H, dd.

J = 2.6, 47.3 Hz); 4.93 (LH, d
, J=3.3 Hz); 5.01--5.30 (8H
, rl); 5.76-5.92 (IH, m);
7.03-7.07 (IH, m); 7.26-7.4
1 (IOH, m).

Infrared absorption spectrum ν,, cm-1 (film)
:1750, 1690° Elemental analysis: Calculated value as C67H106014NF:
C:68.86. H:9.14. N: 1.20.
F: 1.63° Actual value: C: 68.69. H:9
．． 21. N: 1.40. F: 1.63゜luminium'
30.5 g of the compound obtained from -3-0-3'R-3'-MiT-sulfoximi-1-stoyl-4-〇-diphenoxyphosphini 11(c) was treated in the same manner as in 4(d). , the desired compound was obtained in a yield of 31 g (96%).

NMR spectrum (CDCb): δppm0.85
-0.90 (9H, rm); 1.12-1.72 (6
2H, m); 2.06-2.12 (2H, m), 2
．． 35 (IH, dd, J=7.7, 17.6 Hz);
2.52 (IH.

dd, J=5.5, 17.6 t(z); 3.90-
4.35 (6H, o+); 4.73 (IH.

dd, J=9.248.711z); 4.89(IH
, dd, , J=2.6, 47.6 Hz); 4.95
(IH, d, J=3.7 Hz); 5.04-5.2
9 (8H, m); 5.47 (IH, dd, J: 9.2
, 11.0 Hz); 5.77-5.84 (IH, l
1l); 6,81 (LH, dd, J=3.3,8.1
Hz); 7.11-7.37 (20H, m).

Infrared absorption spectrum vrm&w C1” 1 (film); 1745, 1690. T590.1530° Elemental analysis: HNF as C79H115017NFP
P Calculated value: 67.74.8.28.1.00.1.36
．． 2.21゜Actual temperature value: 67.37.8.25.0.8
7.1.31.2.27゜U(ω- Elemental analysis: HNF as C76H111NO17FP
P Calculated value: 67.09.8.22.1.03.1.40
．． 2.28゜ Actual value: 67.20.8.29.0.9
5.1.28.2.21゜15 g of the compound obtained in 11(d) was treated in the same manner as in ■(g) to obtain 1 of the target compound.
Obtained with a yield of 1.6 g (79.6%).

NMR spectrum (CDC13): δppm0.8
5-0.90 (9H, m); 1.14-1.75 (6
2H,m); 2.08-2.13(2f(,m);
2.33 (IH, dd, J=7.7, 16.9 Hz)
; 2.51 (I skin dd, J=4.8, 16.9 Hz
); 3.63 (IH, dd, J=1.1, 4.03
Hz); 3.97 (LH, m); 4.14-4.3
6 (3H, Dri; 4.66-4.77 (IH.

m); 4.89 (IH, dd, J=2.7, 47.6
Hz); 5.02-5.20 (6H.

m); 5.30 (IH, t, J=3.7 Hz);
5.53 (IH, dd, J=9.2°11.0 Hz)
; 6.92 (IH, dd, J=2.9, 7.7 Hz
); 7.12-7.34 (20H, durable.

Infrared absorption spectrum v,, 11+-cm-1 (CH
CI ] ) t3420, 1750.1690.15
90.1530.1490.960° 11.6 g of the compound obtained in 11(e) was treated in the same manner as in 5(f),
The desired compound was obtained in a yield of 8.14 g (87.4:%).

NMR spectrum (C:DC13): δppn10
．． 85-0.90 (9H-); 1.19-1.63 (
62H, m); 2.15-2.20 (2H, m);
2.37 (IH, dd, J=8.4, 17.2 Hz)
; 2.68 (IH, d.

J=8.8 Hz); 3.38 (IH, n+); 3
．． 59-3.62 (2H, m); 4.02-4.05
(3H, m); 4.33-4.40 (IH, m);
4.74 (IH, dd, J=1.1, 48.0 Hz)
; 4.77 (LH, dd, J=9.5, 19.1 H
z); 5.11-5.15 (LH, El); 5.30
(IH, t, J=3.7 Hz); 5.54 (LH,
dd, J = 9.5, 10.3 Hz); 6°83 (I
H, dd, J=3.3, 9.2Hz); 7.15-7
．． 39 (IOH, m).

Infrared absorption spectrum MaxCm-1 (KBr);
1736, 1661.1585.1560.1492゜11 (f) 7.72 g of the compound obtained in 5 (g
), the target compound was quantitatively obtained in a yield of 6.7 g.

NMR spectrum (CDCb): δppm0.85
-0.91 (9H, to); 1.25-2.01 (6
2H, m); 2.38-2.44 (2H, m); 3
．． 19 (2H, d, J=5.86 Hz); 4.11
-4.18 (IH, m); 4.43-4.59 (3H
, m); 4.99-5.07 (LH, to); 5.
15-5.33((2H, m) [5°24(IH, d
d, J=2.0, 48.8 Hz); 5.7
4-5.81 (2H, m); 6.28 (IH, t, J
=9.8 Hz); 8.02 (IH, dd, J=2.
7,9.8 Hz); 8.61 (5H, bs).

Infrared absorption spectrum C, aXcm-1 (KBr); 1
753, 1716.1657.1184.1138.1
117.1068゜Elemental analysis: C48H91FNO1
HNFP as 3P Calculated value: 61.32.9.76, 1.49.2.02
．． 3.29°Actual measurement value: 61.04.9.92.1.6
0.1.92.3.27° Example 12 Ωα 18.7 g of the compound obtained in 1(c) and 21 g of 3-benzyloxy-1-mesyloxytetradecane were dissolved in 150 nil of dry dimethylformamide. 6.9 g of 55'1 sodium hydride was added little by little under water cooling, and then stirred at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate, and acetic acid was added thereto at room temperature for neutralization. The mixture was then washed with a saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The compound obtained here was used in the next reaction without purification.

Actual value: C near 0.56. H:9.87. N:2
．． 37° mass spectrum (m/e); 562 (M”+
1]; 546; 504; 470; 455; 41
5; 399; 362; 350; 309; 28
3; 255; 244; 226; 186; 168
6 g of the compound obtained in 12(a) was treated in the same manner as in 8(b) to obtain 2.99 g of the target compound.

NMR spectrum (CDC13): δppm0.5
7-0.91 (3H, m); 1.17-1.54 (2
8H,n+, [1,39(3H,s); 1.47(3
H, s)); 1.75-1.83 (2H, m
); 2.71 (LH, m); 3.25 (IH, m)
; 3.50-3.86 (6H, nt); 3.92-
4.02 (2H, m); 4.14-4.21 (1) 1
．． m); 4.47 (IH, d, J=11.7 Hz)
; 4.55 (IH, d, J=11.7 Hz); 4
．． 85 (IH, d, J=3.7 Hz); 5.19-
5.34 (2H, n+); 5.85-6.00 (IH
, n+); 7, 24-7.35 (5H, m).

Elemental analysis: Calculated value as C33H55NO6: Cnia 0.55. H:9.87. N: 2.49°12 (
2.76 g of the compound obtained in b) was treated in the same manner as in 1(e) to obtain the target compound in a yield of 3.37 g (78,1%).

NMR spectrum (CDC13): δppm0.8
5-0.90 (6H, DI); 1.25-1.78 (
48H, n+); 2.31 (IH.

dd, J=7.3. ! 5.0 Hz); 2.43 (I
H, dd, J=3.7, 15.0 Hz); 3.36
-3.54 (4H, II); 3.62-3.85 (6
H, [11); 4.00-4.07 (IH, rl);
4.16-4.24 (IH, m); 4.46 (2H
, s); 4.52 (2H, s); 4.78 (IH, d
, J=3.7 Hz); 5.11-5.24 (2H,
m); 5.68-5.86 (IH, m); 6.38
(LH, d, J=9.2 Hz); 7,23-7.3
8 (IOH,!+1).

Infrared absorption spectrum ShinaXam-1 (film)
;33IO, 1642° Elemental analysis: Calculated value as C54H87NO8: C near 3.85. H: 9.98. N: 1.59° Actual value: C near 4.04. H:10.13. N:1.
45° elemental analysis: Calculated value as C51H83NO8:
C Near 3.08. H: 9.98. N: 1.67
゜Actual value: C near 2.72. ) f:10.08.
N: 1.57° Compound 3.37 obtained in 12(c)
g was treated in the same manner as in 8(d), and the target compound was reduced to 1.6
Obtained in a yield of 8 g (52.2%).

NMR spectrum (CDCb): δppm0.86
-0.91 (61-f, m); 4.25-1.77 (
48H, ff1); 2.28 (IH.

dd, J = 7.7, 14.7 Hz); 2.41 (I
H, dd, J=3.344.7 Hz); 3.42-
4.04 (IIH, m); 5-06 (IHts);
6.39 (LH, d, J=8.8 Hz); 7.18
−7.47 (IOH, m).

1.01 g of the compound obtained in 12(d) was dissolved in 15 ml of tetrahydrofuran, and 0.9 g of n-butyllithium (1,6M hexane solution) was dissolved at -78°C under a nitrogen stream.
ml was added. After 2 minutes, a solution of 463 mg of dibenzylchlorophosphate in 5 ml of tetrahydrofuran was added. After 10 minutes, it was neutralized with a solution of 0.5 ml acetic acid in 5 ml tetrahydrofuran. Diluted with ethyl acetate, water,
It was washed with sodium bicarbonate water and brine, and dried over anhydrous magnesilla sulfate 11. After filtration, it was concentrated and purified by silica gel column chromatography to obtain 964 mg (73 phantom target product).

NMR spectrum (CDC13): δppm0.8
8 (6H, t, J=6.6-6°9 Hz); 1.2
-1.8 (42H, m); 1.37 (3H, s); 1
．． 43 (3H, s); 2.24-2.27 (2H, m
); 3.23 (LH, dd, J = 8.4, 10.3 H
z); 3.3-3.5 (2H,!11)'; 3.6-
3.75 (6H, !11); 4.1-4.22 (IH
, m); 4.35-4.47 (4H.

m); 4.99 (2H, d, J=4.8 Hz);
5.03 (2H, d, J=5.1 Hz); 5.73
(IH, dd, J=3.4, 5.7 Hz); 6.4
8 (LH, d, J=8.IH2); 7.30-7.3
3 (20H,!l).

Infrared absorption spectrum νIIIJIX Cl1l-1(
film); 3310, 2930.2860.1660
°NMR spectrum (CDC13:CD30D=1:1
): δppm (heat melting): 0.87-0.91 (
6H, m); 1,27-1.80 (48H, m);
1.41 (3H, s); 1.53 (3H, s); 2
．． 30-2.45 (2H, m); 3.45-4.20 (
IOH, m); 5,54 (LH, m).

Infrared absorption spectrum C,, &xcm-1 (CHCL3
); 3300, 2930.2860.1650.159
0° FAB-mass spectrum: 73-6 [M-l-;
696; 297; 148° 380 nsg of the compound obtained in 12(e) was dissolved in 15 t of tetrahydrofuran.
Dissolved in IIl, add 1.0 g of palladium on carbon,
Hydrogenation was carried out at 3 o'clock. After filtration and concentration, 235 mg
(92%) of the target compound was obtained.

113 mg of the compound obtained in 12(f) was suspended in 30 ml of 80% acetic acid aqueous solution and stirred at room temperature for 1 hour, whereby a white insoluble substance, which was the target compound, was precipitated. By removing the 8-broad acetic acid at room temperature under reduced pressure, a powder of the target compound was quantitatively obtained.

NMR spectrum (CDCb:CDaOD:1:1)
: δppm (heated dissolution, cloudy): 0.89 (6H,
t, J=6.6 Hz); 1.2-1.8 (42H,
m); 2.3-2.4 (2H,!ri; 3.46-3
．． 60 (2H, q, J=8.7 Hz); 3.65-
3.74 (2H, m); 3.77-4.13 (6H,
m); 5.57 (LH, dd, J = 3.2, 6.5 H
z).

Elemental analysis: Calculated value as C34H68NO11P:
C:58.52. H:9.82. N:2.01.
P: 4.44° Actual value: C: 57.71. H:9.
69. N:2.19. P: 4.09° FAB-Mass spectrum (M/Z): 696 [MH]-.

Example 13 Ωα 1.92 g of the compound obtained in (c) was added to 80'
The mixture was dissolved in 60 ml of 1-acetic acid water and stirred at 60°C for 30 minutes. The mixture was concentrated under reduced pressure to obtain 1.83 g (99.9%) of the target compound as a white powder.

NMR spectrum (CDCb): δppm0.88
(6H, t, J=6.6 Hz); 1.2-1.8(
42H,! 1); 2.02 (IH.

); 2.35 (IH, dd, J=7.345.O
Hz); 2.45 (IH, d, J=3.8, 15.
0 Hz); 3.37-3.85 (IIH, yl);
4.06 (IH, tdd.

J: ≦1.5.5, 12.8 Hz); 4.18 (I
H, dt, J = 3.6, 9.9 Hz); 4.46 (
2H, s); 4.50, 4.55 (2H, ABq, J
= 11.0 Hz); 4.76 (IH, d, J = 3.7
Hz); 5.10-5.24 (2H, n+); 5
．． 71-5.83 (IH, m); 6.48 (IH, d
j=9.5 Hz); 7.30-7.33 (IOH,
m).

Infrared absorption spectrum νrmax cm-I (nujol); 3325, 1640° Elemental analysis: Calculated value as C51H83NO8: Cnea 3.08. H:9.98. N: 1.67° Actual value: C near 2.65. H:9.82. N: 1°91
900 mg of the compound obtained in 13(a) was dissolved in 9 ml of methylene chloride, and 185 mg of benzyl chloromethyl ether and 137 mg of tetramethylurea were dissolved.
was added and stirred at room temperature overnight. It was diluted with ethyl acetate, washed successively with aqueous sodium bicarbonate and brine, and dried over magnesium sulfate. After filtration, it was concentrated and purified using a silica gel column. Elution was performed with cyclohexane:ethyl acetate=2=1 to obtain 387 mg (37.7%) of the target compound as a powder. Additionally, 230 mg (25.6%) of raw material was recovered.

NMR spectrum (CDC13): δppm0.8
8 (6H, t, J=6.6 Hz); 1.20-1.
80 (42 skin m); 2.34 (IH, dd, J=7.
3,15.0 Hz); 2.42 (IH, dd, J=
4.0, 15.0Hz); 3.18 (IH, bs);
3.38-3.86 (IOH, n+); 4.06 (
IH.

cfd, J = 5.6, 7.1 Hz); 4.25 (L
H, dt, J = 3.3, 6.8 Hz); 4.46-4
．． 85 (9H, n+); 5.09-5.24 (2H,
n+); 5.73-5.80 (IH, m); 6.4
4 (IH, d, J=9.5 H2); 7.2-7.3
8 (15H,!El).

Infrared absorption spectrum C, □am-1 (Nujol);
3450, 3320.1640° Elemental analysis: Calculated value as C59H91NO9: C near 3.94. H:9.57. N: 1.46° Actual value: C near 3.72. H:9.56. N: 1.56
To a solution of 276 mg of the compound obtained in Step 13 (b) in 3 ml of methylene chloride, 105 mg of N,N-dimethylaminopyridine and 235 mg of diphenylchlorophosphate were added.
mg was added and stirred overnight. Dilute with ethyl acetate,
It was washed successively with sodium bicarbonate water and brine, and dried over anhydrous magnesium sulfate. After filtration, it was concentrated and purified by silica gel column chromatography to quantitatively obtain the target compound.

NMR spectrum (CDCh): δppm0.88
(6H, t, J=6.6 Hz); 1.1-1.8(
42H, ns); 2.2-2.4 (2H, m); 3
．． 30-4.82 (21H, m); 5.13 (IH,
dd, J=1.5°10.3 Hz); 5.20(I
H, dd, JJ, 5, 17.3 Hz); 5.71-
5.86 (IH, m); 6.42 (IH, d, J=8
．． 2 Hz); 7.11-7.65 (25H, ra)
.

Infrared absorption spectrum YrsJ1m cm-1 (nujol); 3340.1645.1590° Elemental analysis: Calculated value as C75H100NO11P:
C near 2.60. H:8.58. N:1.19.
P: 2.64° Actual value: C near 2.62. H:8
．． 40. N:1.10. P: 2.74° Infrared absorption spectrum νnax cm-1 (film): 3300
, 2910.2840.1640.1590°13 (c
) By treating 360 mg of the compound obtained in 8(d), 231 mg of the target compound (65,
4%) yield.

NMR spectrum (CDCh): δppm0.88
(6H, t, J=7.0 Hz); 1.16-1.7
1 (42H, m); 2.17-2.36 (2H, m)
; 2.91-2.92 (IH, d-1ike); 3
．． 39 (IH, m); 3.59-3.87 (6H, E
l); 4.08-4.22 (2H, nx); 4.3
5-4.76 (9H, m); 5.07 (IH, t, J
=3.3 Hz); 6.39 (IH, d.

J=8.8 Hz); 7.11-7.35 (25H,
m).

210 mg of the compound obtained with pyranose 13(d) was added to Example 5.
Treated in the same manner as in (f), 105 mg (68
%) was obtained as a powder.

NMR spectrum (CDC13): δppm0.8
8 (6 skin m); 1,2-1.8 (42H, nl);
2.1-2.4 (2H, m); 3.5-4.2 (9H2
T11); 4.59 (IH, m); 4.92 (IH
, bs); 5.45 (If(, d, J: 3.3 Hz
); 5,77 (IH, bs); 6,69 (IH, d
, J=8.8 Hz); 7.1-7.7(IOH, m
).

Infrared absorption spectrum VffiaX cm-t (Nujol); 3250-3500 (broad), 16
55.1590.1560゜显 peak〕 2-1 gu-2-3'R-3'-hi'guku'su1
100 mg of the compound obtained in 3(e) was dissolved in 10 ml of methanol. 15 rx, g of platinum a-chloride was added, and hydrogenation was carried out at room temperature and 1 atm. After 3-5 hours, filter and concentrate to obtain 59 mg of the desired compound as a white powder.
(I got 70°5.

NMR spectrum (CDC13:CD30D=I:1)
: δppm0.89 (6H, t, J=6.6 Hz
); 1.20-1.83 (42H, m); 2.32
(LH, dd, J=8.8, 15.4 Hz), 2.
43 (IH, dd, J=3.7, 15.4Hz); 3
．． 50-4.75 (IOH,!I); 5.11 (LH
, d, J = 3.3 Hz).

Infrared absorption spectrum νmaw am-1 (nujol); 3300 (broacf), 1650° Example 1
4 Ωα 3.2 g of (2'S, 3'R) compound obtained in 6(a)
was treated in the same manner as '2(b), and the target compound was obtained in 4.12.
g (89.2%).

4 g of the compound obtained in 14(a) was treated in the same manner as in 4(b) to obtain the target compound in a yield of 2.94 g (75.4%).

NMR spectrum (CDC13): δppm, 6
0MHz0.5-2.0 (71H, m); 2.1-2
．． 8 (4H, m); 3.0-5.9 (18H, m);
6.3-6.6 (2H, nz); 7.1-7.3 (
5H, nt).

-O-3'R-3'-benzyloximi "Stoyl-4
6-〇-3'R-3'-benzyloxymirsul-6
-0 - Bejiruoki? 2.73 g of the compound obtained in thiley-〇-copynod 14 (b) was added to 7(C
), and 1.7 g (55,5
%) yield.

NMR spectrum (CDC13): δppm, 6
0MHz0.7-2.0 (71H, m); 2.1-2
．． 7 (48, m); 2.90 (LH, bs); 3.4
-5.5 (20H, n+); 6.2-6.6 (2H,
m); 1.65 g of the compound obtained in (c) was added to 4 (d) every 7.1-7.4 (IOH, m) months.
), 2.0 g of the target compound was quantitatively obtained.

NMR spectrum (CDC13): δppm, 6
0MHz0.5-2.0 (71H, m); 2.1-2
．． 7 (4H, m); 3.5-5.6 (20H, n);
6.2-6.7 (2H, m); 7.1-7.5 (2
08, m).

1.9g of the compound obtained in 14(d) was converted into 1(g)
0.88 g (47,5
%) yield.

NMR spectrum (CDC13): δppm0.8
8 (9H, t, J=6.2-7.0 Hz); 1.1
5-1.70 (62H, n+); 2.20-2.45 (
4H, ox); 3.07 (IH, m); 3.60-
3.82 (3H, m); 4.20-4.90 (IOH
, m); 5.17 (II-1, pc); 5.30 (
IH, t, J = 3.3-3.7 Hz); 5.57 (
IH, dd, J=9.4, 10.8 f(z); 6.
68 (LH, dd, J = 3.5, 8.6 Hz); 7
．． 1-7.35 (20H,!1).

Infrared absorption spectrum νsaw cm-1 (film)
;3450-3300.2920a2860.1740
．． 1680°14(f) 0.78 g of the compound obtained in 14(e) was heated to 7(f
), and 0.37 g (51,
4%) yield.

NMR spectrum (CDC13): δ ppm0.
88 (9H, t, J=6.2-7.0 Hz); 1.
10-1.30 (58H, m); 1.40-1.75 (
4H, m); 2.10-2.33 (4H, DI);
3.50-4.10 (7H, m); 4.70-4.9
8 (3H, m); 5.13-5.40 (2H, m);
5.56 (IH, t, J = 9.5-10.3 Hz);
6.77 (IH, dd, J=3.7°9.2 Hz)
; 7.15-7.38 (IOH, m).

0.29 g of the compound obtained in 14(f) was added to 5(g)
0.25 g of the target compound was quantitatively obtained.

NMR spectrum (CFaC:000): δppm
0.87-0.98 (9H, m); 1,20-1.5
5 (58H, m); 1.55-2.00 (4H, m)
; 2.43-2.64 (2H, m); 2.73-2
．． 94 (2H, at); 4.14-4.55 (5H,!
l); 4.79 (LH, dd, J=9.3, 18.5
Hz); 5.15 (LH, dd, J=1.0, 46.
9'Hz); 5.40-5.78 (3H, ox),
.

FAB-mass spectrum, NEC, (M/Z): 9
3B [M-Old-1 Example I5 3.4 g of (2'R,3'S) compound obtained at 6(a)
was treated in the same manner as in 2(b) to obtain 3.8 g of the target compound.
(77.4%) yield.

NNR spectrum (CDC13): δppm, 6
0M) fzo, 5-2.0 (77H, m); 2.0-
2.8 (4H, m); 3.2-5.6 (16H, m)
; 6.1-6.4 (2H, a+); 7.1-7.4
(5H, m).

2.77 g of the compound obtained in Step 15(b) was added to Step 7(c).
Treated in the same manner as above to obtain 2.36 g (76%) of the target compound.
yield was obtained.

NMR spectrum (CDCb): δppm, 60
MHz0.6-2.0 (71H, m); 2.0-2.
7 (4H, a+); 3.4-6.2 (21H, m.

6.2-6.6 (2H, m); 7.
1-7.5 (IOH, m).

3.68 g of the compound obtained in 15(a) was added to 4(b)
2.97 g (84%') of the target compound
) was obtained with a yield of

2.25 g of the compound obtained with methyl-D-glucopyranoside 15(c) was treated in the same manner as in 4(d) to obtain 2.36 g of the target compound (86.4%
) was obtained with a yield of

NMR spectrum (CDC13): δppm, 6
0MHz0.6-2.0 (71H, m); 2.1-
2.4 (4H, a+); 3.5-6.1 (ZOH, m
); 6.1-6.6 (2H, m); 7.1-7.5
(20H, El).

1.7 g of the compound obtained at long °C σ 15 (e) was treated in the same manner as in 7 (f) to obtain 0.6 g (42,1) of the target compound in an unexpected yield.

2.2 g of the compound obtained in 15(d) was treated in the same manner as in 1(g) to yield 1.83 g (a!5.
'7%) yield.

N to R spectrum (CDC13) ``δ PPEI,
60MHz0.5-2.0 (71H, m); 2.1
-2.6 (4H, m); 3.6-5.9 (17H, m
); 6.75 (IH, bs); 7.1-7.4 (2
0H, m).

0.54 g of the compound obtained in 15(f) was added to 5(g
), and 0.45 g (96-
8%) yield.

NMR spectrum (CF3GOOD): δ ppm
0.87-0.98 (9H, +!+); 1.27-
1.60 (58H, m); 165-1.93 (4H
, m); 2.50-2.60 (2H, tm); 2.
80-2.90 (2H, m); 4.12-4.62 (5
H,! 6); 4.80 (IH, dd, J=9.548
．． 3 Hz); 5.18 (LH, dd, J = 2.7, 4
8.6 Hz); 5.40-5.93 (3H, m).

FAB-mass spectrum, NEG, (Ni/Z):
938 [8-H]-.

5.18 g (20 mmo) of the compound obtained in Example 1(d)
9.93 by dissolving 1) in 150 ml of methylene chloride.
g of (±)-5yn-2-fluoro-3-myristoyloxymyristic acid was added thereto, 4.95 g of N,N'-dicyclohexylcarbodiimide was added, and the mixture was stirred at room temperature for 1 hour. Filtered, concentrated under reduced pressure and diluted with ethyl acetate. Ethyl acetate) E1 layer is dissolved in 1 part of sodium bicarbonate water.
It was washed with brine and dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography and purified with cyclohexane:ethyl acetate = 3:1 to obtain the target compound (2'R,3'S) and (2'
S, 3'R) body each 5.65 g (39.6%)
, with a yield of 5.55 g (38.9%).

[(2'R,3'S) body] NMR spectrum (270MHz, CDC13) δ
ppm0.88 (6H, t, J=6.9 Hz), 1
．． 20-1.38 (388, III), 1.44 (3
H,s), 1.52 (3H,s), 1.60-1.
84 (5H, m), 2.30 (2H.

t), 3.23-3.33 (LH, m), 3.58
-3.85 (4H, m), 3.93 (IH, dd, J
= 5.5, 10.6 Hz), 4.07 (IH, dd
, J=6.2, 12.8Hz), 4.30-4.37
(LH, m), 4.76 (IH, d, J=7.7 H
z).

4.93 (IH, dd, J=2.9, 48.0 Hz)
, 5.20-5.36 (3H, m).

5.79-5.94 (IH, m), 6.44 (LH,
t, J = 5.5 Hz).

[(2'S, 3'R) body] 0.88 (6H, t, J=6.9 Hz), l'20
-1.38 (38H, m), 1.45 (3H, s),
1.52 (3H, s), 1.56-1.76 (5H
, m), 2.29 (2H.

t), 3.30-3.41 (2H, m), 3.57
(LH, t, J=9.2 Hz).

3.80 (, tH, t, J=10.6 Hz), 3.
93 (IH, dd, J=5.5, 11.0Hz), 4
．． 05-4.16 (2H, m), 4.29-4.36
(LH, m), 4.77 (IH, d, J=8.l f
(z), 4.89 (IH, dd, J=2.2,48.
0 Hz).

5.20-5.34 (38, m), 5.80-5.8
9 (LH, m), 6.52 (IH, t.

J = 5.5 Hz).

Compound (2'R,3'S) compound 2 obtained in 16(a)
g (2.8 mmol) was dissolved in 30 ml of methylene chloride, 728 mg of myristic acid chloride was added, 313 mg of triethylamine was added, and the mixture was dissolved at room temperature for 1.
Stir for hours.

It was concentrated, diluted with ethyl acetate, washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with cyclohexane:ethyl acetate=5:1 to obtain the target compound in a yield of 1.35 g (52.1%). Ta.

Infrared absorption spectrum v nrax (CHCL3):
1740, 16i95 cm-1° mass spectrum MHz: 924 (M”+1),
909.883°867, 737.724.655.6
38.610.526.513.452°NMR spectrum (270MHz, CDC13) δppm0.8
8 (9H, t, J=6.6 Hz), 1.13-1.
67(70H,m[1,36(3H.

s), 1.46 (3H, s)]), 2.2
5-2.35 (4H, m).

3.32-3.41 (LH, m), 3.66-3.8
5 (3H, m), 3.95 (IH, dd.

J = 5.5, 10.6 Hz), 4.05 (IH, d
d, J = 6.242.8 Hz).

4.26-4.34 (IH, to), 4.74-4.
93 (2H, m), 5.15-5.29 (4H, m)
, 5.75-5.89 (IH, m), 6.34 (I
H, dd, J = 4.4°8.8 Hz).

Elemental analysis: C5J (CHNF as seFNO9 Theoretical value 70.17% 10.69% 1.52$
2.06% Analysis value 70.41% 10.58% 1.47% 1.99%16 The compound obtained in (b) was treated in the same manner as in Example 4(b) to obtain the target compound 2.
g (80.4%).

NMR spectrum (60MH2, CDC13) δpp
m0.66-1.91 (74H, m), 2.09-2
．． 55 (4H, m), 2.87-6.16 (15H,
m), 6.54 (LH, m).

1.9 g (2.15 m
mol) in 20 ml of methylene chloride, 550
Add 5 mg of benzyloxychloroformate and 327 mg of triethylamine at room temperature.
Stir for hours. It was concentrated and diluted with ethyl acetate. Wash the ethyl acetate layer with sodium bicarbonate water and brine,
It was dried with anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with cyclohexane:ethyl acetate=3:1 to obtain the target compound in a yield of 660 nxg (30.2%).

N! lI! R spectrum (270MH2, CDC13)
δppm0.88 (9H, t, J=6.9 Hz),
1.25-1.65 (66H, m), 2.25-2.
36 (4H, m), 2.82 (IH, s), 3
．． 59-3.66 (2H, n+).

4.03 (LH, dd, J=6.2, 12.8 Hz)
, 4.27 (IH, dd, J=5.1°12.8H
z), 4.42-4.52 (IH, m), 4.81
(IH, dd, J=3.7°47.6 Hz), 4.
84 (IH, d, J=8.1 Hz), 5.14-5
．． 27 (6H.

m), 5.76-5.89 (IH, m), 6.37
(IH, dd, J=4.4, 8.1 Hz), 7.3
4-7.40 (5H, ox).

16 (d) 600 mg (0,58
9 muol) was dissolved in 20 ml of methylene chloride, 474.8 mg of diphenylchlorophosphate was added, and further 62.6 mg of triethylamine was added, and the mixture was stirred at room temperature overnight.

It was concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with cyclohexane:ethyl acetate=5:1 to obtain the target compound in a yield of 600 mg (81.4%).

Infrared absorption spectrum v max (CHCL3):
1743, 1690 cm-1 NMR spectrum (270MH7, CDC13) δp
pm0.88 (9H, t, J-6,9Hz), 1.0
5-1.73 (64H, l11), 2.11-2.3
(4H, m), 3.46-3.56 (1 skin m),
3.77-3.82 (IH, m).

4.03 (LH, dd, J=6.2, 12.8)iz
), 4.19-4.38 (3H, m).

4.63-4.89 (2H, m), 5.01-5.2
6 (6H, m), 5.64-5.87 (2H, m),
6.37 (IH, dd, J-4, 4, 7, 7Hz),
7.11-'134 (15H, m).

Elemental analysis: CHN as C71H1゜9FNO□4P
F P Theoretical value 68.19% 8.79% 1.12% 1
．． 52% 2.48% Analysis value 67.97% 8.5
6% 1.21% 1.47% 2.47%
The compound obtained in 0-16(e) was treated in the same manner as in Example 1(g) to obtain the target compound in a yield of 490 nag (84.3%).

NMR spectrum (270MHz, CDC: 13) δ
ppm0.88 (9H, t, J=7.0 Hz), 1
．． 11-1. ．． 66 (64H, m), 2.11-2.
29 (4H, m), 3.36 (LH, s), 4.1
3-4.39 (4H, m).

4.71-5.56 (7H, o+), 6.70 (LH
, dd, J = 3.3, 8.1 Hz).

7.11-7.35(15H,m)-16 (f) 490 mg of the compound obtained in 30 rnl
was dissolved in tetrahydrofuran, 1 g of 10% palladium on carbon was added, and catalytic reduction was carried out at room temperature for 2 hours. After filtration, tetrahydrofuran was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with ethyl acetate to obtain the target compound in a yield of 270 mg (75.9%).

Infrared absorption spectrum v max (CIC13):
1735, 1685 cm-1 Elemental analysis: CHN as C6oH99FNOt□P
FP Theoretical value 66.95% 9.27'% 1.30%
1.76% 2.88% Analysis value 67.23%,
9.27% 1.35% 1.911 2.8L
The compound obtained in %16 (g) was treated in the same manner as in Example 5 (g) to obtain the target compound in a yield of 190 mg (96, 2%).

Mass spectrum NEG, FAB/MS; M/Z:
Compound (2) obtained with 922(ni-H)-016(a)
'S, 3'R) 2.9 g (4.06 mmol) was dissolved in 30 ml of methylene chloride, and 1.02 g (4.06 mmol) of myristic acid was dissolved in 30 ml of methylene chloride.
Then, 1 g of N,N'-dicyclohexylcarbodiimide was added, and the mixture was stirred at room temperature for 1 hour, but the reaction did not proceed, so 50 mg of 4-dimethylaminopyridine was added and 1 g of N,N'-dicyclohexylcarbodiimide was added at room temperature. Stir for hours. It was concentrated under reduced pressure, diluted with ethyl acetate, and the ethyl acetate layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified using cyclohexane:ethyl acetate=5:1 to quantitatively obtain the target compound.

NMR spectrum (60MHz, CDCb) δpp
m0.66-2.01 (79H, m), 2.05-2
．． 61 (4H, m), 3.30-6.23 (14H,
m), 6.85 (LH, m).

The compound obtained in Example 17(a) was treated in the same manner as in Example 4(b) to obtain the target compound in a yield of 3.08 g (84.7%).

2.7 g (3,05tc) of the compound obtained in 17(b)
llIol) was dissolved in 50rnl of methylene chloride, 0.525 g of benzyl chloromethyl ether was added, and further 0.355 g of tetramethylurea was added, followed by reflux for 6 hours.

Methylene chloride was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with cyclohexane:ethyl acetate=3:1 to obtain the target compound in a yield of 2.08 g (67.8%).

Infrared absorption spectrum v max (C[(C13)
:3430, 1738.1695 cm-1 Mass spectrum M/Z: 986.928.834.775°717, 596.509.456.383.354.2
98.285°268° NMR spectrum (270Mi (z, CDC13)
δ ppm0088 (9H, t, J=6.9 Hz)
, 1.20-1.73 (65H, l), 2.24-
2.37 (4H, m), 3.47-3.51 (IH,
m), 3.74 (LH, t, J=9.5Hz), 3
．． 89-4.11 (4H, m), 4.26-433 (
LH, a2), 4.59 (LH, d, J=8.4 H
z), 4.63 (2 skin s), 4.79 (E, dd
, J=4.3,48.4 Hz), 4.81(2[(
, s), 5.03 (LH, dd, J=9.2°10.
6 Hz), 5.15-5.30 (3H, m), 5
．． 80-5.88 (LH, m).

6.36 (LH, dd, J=4.4, 9.2 Hz)
,, 7.29-7.36 (5H, m).

↓J Rikiwoshi2-1-'-2-2'S3'R-2'-phleorostyloxymyristoylamide]-3-0-myris1
The compound obtained in 7(c) was treated in the same manner as in Example 16(e) to quantitatively obtain the target compound.

Infrared absorption spectrum v max (CHCL3):
3430, 1740.1695 cm-1 Mass spectrum MHz: 1014.994.758.670° 580, 440.322.268° NMR spectrum (2'lOMHz, CDC13)
δppm0.88 (9H, t, J=6.9 H2),
1.10-1.68 (65H, Ell), 2.08-
2.31 (3H, m), 3.65-3.69 (2H,
m), 3.78-3.84 (LH, m).

4.03-4.11 (2H, m), 4.25-4.3
2 (LH, m), 4.50-4.85 (7H, m),
5.15-5.39 (4H, m), 5.76-5.
83 (LH, m).

6.38 (LH, dd, J-4, 8, 9, 2Hz),
7-13-7.44 (15H, m).

The compound obtained in Example 1 (g
) to obtain the target compound in a yield of 1.58 g (71 g).

NHR spectrum (60MHz, CDC13) δp
pm0.63-2.42 (77H, m), 3.55-
5.78(14H,m[4,54(2H,s).

4.66 (2H, s)), 6.70 (IH,
m), 7.00-7.53 (15H, m) - 1.44 g (1.2 mm
ol) was dissolved in 30 ml of methanol, 10% palladium carbon Ig was added, and catalytic reduction was performed at 40 to 45°C for 3 hours.

After filtration, methanol was distilled off under reduced pressure, and the residue was applied to a silica gel column and purified with cyclohexane:ethyl acetate=1:1 to obtain the target compound in a yield of 715 mg (55.2%).

Infrared absorption spectrum v max (CHCL3):
3440, 1740.1690 cm-f elemental analysis:
CHNFP as C6oHs9FNOt2P Theoretical value 66.95% 9.27% 1-30%
1.76 stones 2.88% Analysis value 66.96% 9.
30% 1.17bu 1.74bu 2.81% Asami ngen-17(f) was treated in the same manner as in Example 5(g) to obtain 420 mg (89%) of the target compound. ) was obtained with a yield of

Mass spectrum NEC, FAB/evil! (/Z:
922(M-H)-''.

Example 18(a) (R,5)-3-benzyloxycarbonyloxy-2
, 2.2 g of 2-difluoromyristic acid, 20 ml
Oxalic acid chloride 2 dissolved in dry dichloromethane of
ml, 1 drop of N,N-dimethylformamide was added, and the mixture was stirred at room temperature for 1 hour. Dichloromethane was distilled off under reduced pressure to obtain acid chloride. 1.51 g of allyl 2-deoxy-2-amino-4,6-0-isopropylidene-β-D-glucopyranoside obtained in Example 1(d),
It was dissolved in 20 rnl of dry dichloromethane, 700 mg of triethylamine was added, and the acid loride was added under water cooling. The mixture was stirred at room temperature for 1 hour, and dichloromethane was distilled off under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, the residue was subjected to silica gel chromatography, and cyclohexane:
Purification with ethyl acetate (2:1) yielded the target compound 2.64
g (75.8%).

NMR spectrum (270MHz, CDCb) δP
PE110.88 (3H, t, J=6.2-7.0H
z), 1.25-1.61 (24H, m-[1,45
(3) f, s), including 1.52 (3H, s)] L
172-1-79 (2H, m), 2.95 (0-58
, d, J=3.3Hz), 3.11 (0,5H, d,
J=3.3Hz), 3.21-3.60 (3H, m)
, 3.76-4.13 (4H, r++).

4.23-4.33 (1!I, m), 4.70 (0-
5H, d, J=8.4Hz), 4.81 (0,5H,
d, J=8.4 Hz), 5.14-5.31. (5
H, m), 5.75-5.91 (LH, m), 6.
47-6.54 (IH, m), 7.30-7.40 (
5H, m).

Infrared absorption spectrum v max (CHCL3):
3430, 2925.2850.1755.1705.
1535.1380°1263 cm-1 Mass spectrum M/Z: 655 (M, 640
．． 597.532°468, 385.360.242.
227.184.143.108.1.01゜91,6
9.43゜Elemental analysis: CHNF as C34H5□F2N09 Theoretical value 62.27% 7,86 2.14% 5
．． 79% analysis value 62.20% 7.76% 2.
230 mg (0.5 mmol) of (R)-3-myristoyloxymyristic acid in 4 ml of dichloromethane with 0.5 ml of oxalyl chloride.
After treatment for a period of time and acid chloride, excess oxalyl chloride and solvent are removed and dried under reduced pressure. Example 18 (
262 mg (0.4 mmol) of the compound obtained in a)
, 50 mg of triethylamine and 5 m of dichloromethane
After cooling sufficiently on ice, 5 ml of the above dichloromethane solution of acid chloride was added dropwise. The raw material ran out after 3 hours, so the solvent was removed under reduced pressure, diluted with ethyl acetate, and post-treated with 5 hydrogen carbonate 1 helium aqueous solution and saturated saline solution, and column chromatography (silica gel 20
g, developing solvent dichlorohexane: ethyl acetate = 5:1)
The yield was 325.8 mg (74.3 mg).
%）

NMR spectrum (270MHz, CDC11) δ
ppm0.85-0.90 (9t(,m), 1.20
-1.80 (68H, m), 2.20-2.31 (2
! (,m), 2.43-2.66(2)Lm), 3
．． 35 (IH, m), 3.68-4.07 (6H, m
), 4.26 (LH, m), 4-58 (LH, m)
, 5.11-5.41 (7H', rn), 5.74 (
IH, m), 6.58 (LH, n+), 7.29-
7.38 (5H, m).

Infrared absorption spectrum νmax (liquid film): 3350,
2925.2850.1780.1710 CO! -1
ylamide-3-0-R-3'-myristoyloxymyristoyl--D-glucopyranoside 18 50 ml of 8-decoy acetic acid was added to 0.2 g of the metal compound obtained in (b), and the mixture was heated at 60°C for 50 minutes. Stir. After removing acetic acid under reduced pressure and drying with a vacuum pump, column chromatography [silica gel 15
g, developing solvent (cyclohexane: ethyl acetate = 2:1)
]. The yield was 0.11 g (57.9%).

In this reaction, it is better to use as much acetic acid as possible to complete the reaction quickly; if the amount of acetic acid is small, by-products are formed and the yield is reduced.

NMR spectrum (270MHz, CDCb) δ
ppm0.85-0.90 (9H, t, J=6.4-6
．． 8 Hz), 1.18-1.42 (47H.

m), 1.43-1.80 (15H, m), 1.9
0-2.00(1[(,m), 2.09(LH,t,
J=5.9-6.4 Hz), 2.25-2.32(
2H, m), 2.41-2゜50 (2H, 01),
3.37-3.53 (IH, m), 3.63-3.7
0 (2H, m).

3.78-4.08 (5H, m), 4.21-4.3
4 (IH, m), 4.53 (0,4H.

d, J = 8-3 Hz), 4.59 (0,6H, d,
J = 8.3 Hz), 4.92-5.36 (7H, m
), 5.74-5.88 (LH, m), 6.59 (
0,6H,d, J=8.8 Hz), 6.69(0,
4H, d, J=8.8 Hz), 7.35-7.39
(5H.

ll11).

Infrared absorption spectrum νmax (nujol) = 33
50.3450.3300.2950.1760.16
90.1620°1550 am-1 Elemental analysis: Analysis value as C6tHxooF2NOxz:
C67,24, H9,04, N 1.68. F3
．． 41 (%) Theoretical value: C68,00, H9,28,
N 1.30. F 3.53 (%) 120 mg of the compound obtained in (c) (0,11!111110
1) and benzyloxycarbonyl chloride 25.4
mg (1.3 equivalents) is dissolved in 20 ml of dichloromethane and cooled on ice. Dimethylaminopyridine 17.2 mg
(1.5 equivalents) and stirred for 30 minutes, then returned to room temperature and stirred for 2 hours. Column chromatography [100 g of silica gel, developing solvent (cyclohexane: ethyl acetate =
2: 1)], and the target product was purified with a yield of 80 mg (5
9.2%), and a substance protected at both the 4th and 6th positions was obtained in a yield of 36 mg (26.7%).

NMR spectrum (270MHz, CDCb) δpp
m0.88 (9H, t, J=6.35-6.83 Hz
), 1.25-1.73 (62H, ns).

2.24-2.31 (2H, m), 2.41-2.4
8 (2H, m), 3.52-3.69 (4f (, m)
, 3.90-4.02 (3H, m).

4.18-4.30 (LH, m), 4.42-4.
57 (3H, nu), 5.02-5.25 (7H,
m), 5.68-5.85 (LH, nri, 6.48
-6.52 (1 skin d).

6.58-6.65 (IH, d), 7.32-7.4
0 (IOH, III).

Infrared absorption spectrum νmax (nujol): 35
00, 3300.2900.2850.1720.16
90.1540m-1 Elemental analysis: Analysis value as CF, 9HtogFzNOt4: C67,19,H8,75,NO,89,F
2.99 (%) Theoretical value: C68,41, H8,75
, N 1.16. F 3.14 (Phantomyloxymyristoylamido-4-〇-diphenoxyphosphinyl-2
--Oxy-3-0-R-3-mi'S18 0.5 g of the compound obtained in (d), diphenylphosphoryl chloride, dimethylaminopyridine.

Add 1g of each in excess and add 50ml of tetrahydrofuran
was used as a solvent and heated under reflux for 3 hours. The solvent was removed under reduced pressure, diluted with ethyl acetate, and post-treated with an aqueous sodium bicarbonate solution and a saturated saline solution. Column chromatography [30 g of silica gel, developing solvent (cyclohexane:
Purified with ethyl acetate = 3:1), yield 0.62 g
(Obtained with 97.5 illusions.

NMR spectrum (270MHz, CDC1a) δp
pm0.90 (9H, t, J=6.8 Hz), 1.
14-1.75 (62H, m), 2.12-2.41
(3H, Dri, 3.61-3.83 (3H, m),
3.91-4.04 (LH, m).

4.13-4.23 (2H, m), 4.30-4.3
8 (IH, m), 4.69 (LH, ddd, J=9.
0,9. O40, OHz), 4.85 (LH, d, J
= 7.0 Hz).

4.99-5.39 (7H, shoes) y 5,47-5.6
3 (2H, I!I), 5.67-5.85 (LH, m
), 6.80 (LH, d, J=7.0 Hz), 6.
95 (LH, d, J=7.0Hz), 7.10-7.
36(20H, m)-Infrared absorption spectrum νmax
(Liquid film): 3300, 2900.2850.1750.
1700.1590.1540m-1 Elemental analysis: CH as C81H11SF2NO17P
NFP analysis value: 66.15.7.92.1.03.2.4
52.13 (%) Theoretical value: 67.43.8.0
0.0.97.2.632.15. (%) 18 (
To 50 nag of the compound obtained in e), 30 rng of 1,5-cyclooctadiene bis[methyldiphenylphosphine]iridium hexafluorophosphate (5
% mole) in 5 ml of tetrahydrofuran, and the atmosphere was replaced with nitrogen and then with hydrogen. When the color of the solution changes, the atmosphere is quickly replaced with nitrogen, and the mixture is stirred at room temperature for 3 hours. concentrated hydrochloric acid 1
[111 was added, stirred at 50°C for 2 hours, and purified by preparative thin layer chromatography (1 mm) to obtain 40 mg (82
, I got one vision.

NMR spectrum (270MHz, CDC13) δp
pm (R, S mixture) 0.83-0.90 (91 (, t,
J2 6.5-6.8 Hz), 1.16-1.7
4 (62H.

m), 2.09-2.18 (2H, m), 2.32
-2.49 (2H, n+), 2.73-2°74 (0
,5H,n+), 3.28-3.29(0,5H,m
), 4.01-4.38 (4H.

m), 4.63-4.74 (LH, m), 4.89
-5.23 (8H, m), 5.33-5°47 (LH
, us), 6.72-6.73 (LH, m), 7.
12-7.37 (20H, m).

Infrared absorption spectrum νmax (liquid film): 3350,
2925.2850.1750.1710.1590.
1540°1490, 1460 cm=1 Elemental analysis: HN as C7eHtx□F2N01°P
FP analysis value: 69.73.7.37.0.71.2.4
3.2.05 (%) Theoretical value: 66.74.7.
97.0.98.2.63.2.21 (%) ↓ Crawling force σ 4-0-diphenoxyphosphinyl-2--oxy-2
-R3-2'2'-difluoro-3'-hydroxymiT To 2 ml of tetrahydrofuran, 30 mg of the compound obtained in 18 (f) was added, and 10'1 palladium carbon 2
0 mg was added thereto, the mixture was replaced with hydrogen using an aspirator, and the mixture was stirred at room temperature for 6 hours, and then left in the apparatus overnight.

Preparative thin layer chromatography [1 mm, developed with developing solvent (cyclohexane: ethyl acetate = 1:1), 10 mg each of two target compounds in which the substituent at the 2-position is R or S.
(41.2%) was obtained.

[2H form (lower Rf)] NMR spectrum (270MHz, CDCl:l) δ
ppm0.85-0.90 (9H, t, J=6.34
-6.36 Hz).

1.20-1.68 (62H, m), 2.17-2.
23 (2H, (11), 2.34-2.47 (2H,
m), 3.10 (IH, d, J=4.5 R2),
3.18-3.27 (2H, DI).

3.54-3.61 (IH, m), 3.92-4.0
3 (3H, m), 4.27-4.36 (IH, m),
4.78 (LH, q, J = 9.2 Hz) 25.02
-5.11 (IH, I!+).

5.36 (IH, t, J=3.42 Hz), 5.5
3 (IH, t, J = 9.28 Hz).

6.87-6.91 (IH, m), 7.14-7.3
9 (IOH, m).

Infrared absorption spectrum νmax (nujol): 35
00, 3450.3375.2900.2850.17
30.1680゜1600 cm-1 [23 bodies (one with higher Rf) - NMR spectrum (270MHz, CDC13) δp
pm0.85-0.90 (9H, t, J=6.3-6'
, 41 Hz).

1.21-1.68 (62H, m), 2.17-2.
23 (2H, m), 2.34-2.50 (2H, m)
, 3.08 (IH, d, J=4.4 Hz), 3.
18-3.29 (2H, n+).

3.54-3.61 (LH, m), 3.94-4.0
0 (3H, DI), 4.27-4.36 (1 skin m),
4.79 (LH, q, J=9.4 Hz), 5.0
2-5.12 (LH, m).

5.36 (LH, t, J=3.42 Hz), 5.5
3 (IH, t, J = 9.73 Hz).

6.92-7.01 (If(,m), 7.14-7.
39 (IOH, m).

Infrared absorption spectrum νmax (nujol): 35
00, 3450.3375.2900.2850.17
30.1680゜1600 cm (HydroxymiI Stoylamide-3-0-R-3-Mi■
60 mg of each of the compounds obtained in 18 (g) and 5 mg of platinum oxide were added to 2 ml of sulfuroximej-stoyl-D-glucopyratetrahydrofuran, hydrogen substitution was performed using an aspirator, and the mixture was stirred at room temperature for 3 hours. Platinum oxide is removed by filtration, tetrahydrofuran is removed under reduced pressure, and Rf is extracted from the raw material compound with the higher Rf value among the two target compounds in which the 2-position substituent is R or S.
The one with the higher value is 50 IIIg (95%), and the one with the lower Rf value is 52 mg (97%) from the raw material compound with the lower Rf value.
) was obtained [developing solvent (chloroform: ethanol: ethyl acetate: water = 8:5:2:1)].

[2R form (lower Rf)] NMR spectrum (270 MHz, ds-pyridine decaqueous water) δpPm: 0.85-0.90 (9H, ox
), 1.14-2.04 (62H, m).

2.39-2.48 (2H, o+), 3.05-3.
l4 (LH, Ilm), 3.28-3.37 (IH,
m), 4.07-4.11 (LH, m), 4.49
-4.66 (3H, m).

4.88-4.98 (IH, m), 5.18-5.2
9 (LH, m), 5.71-5.81 (2H, m),
6.17-6.32 (LH, DI).

Infrared absorption spectrum νmax (nujol): 35
00, 3350.2900.2850.1720.16
80.1590°1540.1490.1460 cm
-1 [23 bodies (one with higher Rf)] NMR spectrum (270 MHz, ds-pyridine decaycetate) δppm: 0,88-0.97 (9H, l1
l), 1.24-2.02 (62H, DI).

2.33-2.48 (2H, m), 2.92-3.0
1 (2H, DI), 3.36-3.59 (LH, m)
, 4.11-4.22 (IH, m), 4.53-4
．． 69 (3H, m).

4.93-5.04 (LH,!1), 5.49-5.
56 (IH, El), 5.68-5.74 (IH, m
), “5.82-5.83 (LH, m), 6.26-
6.38 (LH, m).

Infrared absorption spectrum νmaX (nujol) = 35
00, 3350.2900.2850.1720.16
80.1590°1540, 1490.1460 cm
-1 Example 19 8 of 1 Ethylamine 1 (h), 2 (d), 3 (c), 4 (f), 5 (g),
6(h), 7(g), 9(b), 10(g), 11(g
), 12 (g), 13 (f), 14 (g), 15 (
If it is necessary to obtain water-soluble triethylamine salts of the phosphoric acid compounds obtained in g), 16(h), 17(g) and 18(h), the same operation as in Example 8(f) is carried out.

Claims (3)

[Claims] (1) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, one of R^1 and R^4 is a hydrogen atom, and a group having the formula -P(O)(OH)_2 or represents a hydroxyl group-protecting group, and the other represents a group having the formula -P(O)(OH)_2. Among R^2 and R^3, one represents an aliphatic acyl group having 6 to 20 carbon atoms, which may have a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 6 to 20 carbon atoms, and the other has a halogen atom and a hydroxyl group or an aliphatic acyl group having 6 to 20 carbon atoms, or a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 6 to 20 carbon atoms. represents an optionally alkyl group having 6 to 20 carbon atoms. R^5 represents a hydrogen atom or a hydroxyl group-protecting group] and salts thereof. (2) In claim 1, one of R^2 and R^3 is a halogen atom, a hydroxyl group, or has a carbon number of 6 to 20.
6 carbon atoms, which may have 6 aliphatic acyloxy groups
Compounds having 6 to 20 aliphatic acyl groups, the other of which is a halogen atom and a 6 to 20 aliphatic acyl group having a hydroxyl group or an aliphatic acyloxy group having 6 to 20 carbon atoms, and salts thereof . (3) In claim 1, R^2 represents an aliphatic acyl group having 6 to 20 carbon atoms, which may have a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 6 to 20 carbon atoms; A compound in which R^3 represents an alkyl group having 6 to 20 carbon atoms, which may have a halogen atom, a hydroxyl group, or an aliphatic acyloxy group having 6 to 20 carbon atoms, and a salt thereof.