JP2839921B2 - Lipid A monosaccharide analogues - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Object] (Industrial application field) The present invention relates to a novel lipid A monosaccharide analog having an antitumor effect based on macrophage activation and a salt thereof.

(Prior art) The outermost layer of the cell wall of Gram-negative bacteria obtained from intestinal bacteria contains a toxic component (endotoxin) that is not secreted outside the cells. In addition, it exhibits various biological activities such as immunoadjuvant activity, macrophage activity, mitogen activity, pyrogenic effect, tumor necrosis effect, antibody production enhancing effect, and TNF-inducing effect related to the self-defense of the living body.

Such endotoxins consist of lipopolysaccharide, so-called lipid A
It has been found that the moiety is the active center of endotoxin activity.

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

Based on these results, a derivative of lipid A, X or Y was synthesized and its activity was examined (for example, Imoto et al., Tetrahedron Lett., 26, 154).
5 (1985) or Kiso et al., Carbohydrate Research, 162,127
(1987)).

However, since it is a bacterial endotoxin itself, there remain problems such as lethal toxicity, pyrogenic action, leukopenia, and induction of autoimmune diseases.

(Problems to be Solved by the Invention) The present inventors have conducted intensive studies over many years on the synthesis of lipid A monosaccharide analogs having macrophage activating activity and their pharmacological activities. Novel lipid A monomers having a structure different from that of the monosaccharide derivative, that is, having a halogen atom and a hydroxyl group or an aliphatic acyl group having 6 to 20 carbon atoms substituted by an aliphatic acyloxy group having 6 to 20 carbon atoms. A novel lipid A monosaccharide analog in which a saccharide analog or an alkyl group having 6 to 20 carbon atoms is ether-bonded to the 3-position hydroxyl group has an excellent macrophage activating effect;
The present inventors have found that they are useful as immunostimulating agents or antitumor agents, and have completed the present invention.

[Constitution] The novel lipid A monosaccharide analog of the present invention has a general formula: Wherein ^one of R ¹ and R ⁴ is a hydrogen atom,
A group having (O) (OH) ₂ or a protecting group for a hydroxyl group is shown, and the other group is a group having formula -P (O) (OH) ₂ .

One of R ² and R ³ represents a halogen atom, a hydroxyl group or an aliphatic acyl group having 6 to 20 carbon atoms which may have an aliphatic acyloxy group having 6 to 20 carbon atoms, and the other represents a halogen atom. Atom and hydroxyl group or carbon number 6-20
Aliphatic acyloxy groups having 6 to 20 carbon atoms or 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. Shows an alkyl group.

R ⁵ represents a hydrogen atom or a protecting group for a hydroxyl group].

In the above general formula (I), the term “protecting group for hydroxyl group” in the definition of R ¹ , R ⁴ and R ⁵ indicates a protecting group in a reaction and a protecting group for administration to a living body, for example, formyl, acetyl, Alkylcarbonyl groups such as propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, lauroyl, myristoyl, tridecanoyl, palmitoyl, stearoyl, alkyl halides such as chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl Aliphatic acyl groups such as carbonyl group, lower alkoxyalkylcarbonyl group such as methoxyacetyl, unsaturated alkylcarbonyl group such as (E) -2-methyl-2-butenoyl; benzoyl, α-naphthoyl, β-naphthoyl Arylcarbonyl groups such as 2-bromobenzoyl, 4
Halogenated arylcarbonyl groups such as -chlorobenzoyl, lower alkylated arylcarbonyl groups such as 2,4,6-trimethylbenzoyl, 4-toluoyl, 4-
Lower alkoxylated arylcarbonyl groups such as anisoyl, nitrated arylcarbonyl groups such as 4-nitrobenzoyl and 2-nitrobenzoyl, lower alkoxycarbonylated arylcarbonyl groups such as 2- (methoxycarbonyl) benzoyl, 4-phenyl Aromatic acyl groups such as arylated aralcarbonyl groups such as benzoyl; tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl A tetrahydropyranyl or tetrahydrothiopyranyl group such as 4-methoxytetrahydrothiopyran-4-yl; tetrahydrofuranyl or tetrahydrothiol such as tetrahydrofuran-2-yl or tetrahydrothiofuran-2-yl Furanyl group; tri-lower alkylsilyl group such as trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl, triisopropylsilyl, diphenylmethylsilyl, diphenyl-t-butylsilyl, Silyl groups such as tri-lower alkylsilyl groups substituted with one or two aryl groups such as diphenylisopropylsilyl and phenyldiisopropylsilyl; methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl , Isopropoxymethyl, butoxymethyl, t
Lower alkoxymethyl groups such as butoxymethyl, 2
An alkoxymethyl group such as a lower alkoxylated lower alkoxymethyl group such as -methoxyethoxymethyl, a halogenated lower alkoxymethyl group such as 2,2,2-trichloroethoxymethyl or bis (2-chloroethoxy) methyl;
-Ethoxyethyl, 1-methyl-1-methoxyethyl,
Substituted ethyl groups such as lower alkoxylated ethyl groups such as 1- (isopropoxy) ethyl, halogenated ethyl groups such as 2,2,2-trichloroethyl, and arylselenyl ethyl groups such as 2- (phenylzelenyl) ethyl Benzyl, phenethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9
Lower alkyl substituted with one to three aryls such as anthrylmethyl, 4-methylbenzyl, 2,
4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-
1 to 3 aryl groups in which the aryl ring is substituted by lower alkyl, lower alkoxy, nitro, halogen, cyano groups such as cyanobenzyl, 4-cyanobenzyldiphenylmethyl, bis (2-nitrophenyl) methyl, piperonyl; Aralkyl groups such as substituted lower alkyl groups; lower alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl and isobutoxycarbonyl, and 2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl; An alkoxycarbonyl group such as a lower alkoxycarbonyl group substituted with a halogen or a tri-lower alkylsilyl group; an alkenyloxycarbonyl group such as vinyloxycarbonyl and allyloxycarbonyl; benzyloxycarbonyl; The aryl ring is substituted by one or two lower alkoxy or nitro groups such as -methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl; Aralkyloxycarbonyl groups; protecting groups in reactions such as allyl groups; formulas —COCH ₂ CH ₂ COOH, —COCH ₂ CH
An acyl group having a terminal carboxy group, such as a compound having (OH) COOH or -COCH = CH-COOH, or a protecting group for administration to a living body, such as pivaloyloxymethyloxycarbonyl, can be mentioned.

In the definition of R ² and R ³ , “an aliphatic acyl group having 6 to 20 carbon atoms” and “an aliphatic acyl group having 6 to 20 carbon atoms” of “an aliphatic acyl group having 6 to 20 carbon atoms” Is, for example, pentylcarbonyl, hexylcarbonyl,
Heptylcarbonyl, octylcarbonyl, nonylcarbonyl, decylcarbonyl, 3-methylnonylcarbonyl, 8-methylnonylcarbonyl, 3-ethyloctylcarbonyl, 3,7-dimethyloctylcarbonyl, undecylcarbonyl, dodecylcarbonyl, tridecylcarbonyl, tetra Decylcarbonyl, pentadecylcarbonyl, hexadecylcarbonyl, 1-methylpentadecylcarbonyl, 14-methylpentadecylcarbonyl, 13,13-dimethyltetradecylcarbonyl, heptadecylcarbonyl, 15-methylhexadecylcarbonyl, octadecylcarbonyl, -Methylheptadecylcarbonyl and nonadecylcarbonyl are preferred, and are preferably straight-chain or branched-chain aliphatic acyl groups having 10 to 16 carbon atoms.

As the "halogen atom" in the definition of R ² and R ³ ,
Indicates fluorine, chlorine, bromine or iodine.

"An alkyl group having 6 to 20 carbon atoms" in the definition of R ³
As 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, 4,8,12-trimethyltridecyl, 1-methylpentadecyl, 14-methylpentadecyl, 13,13-dimethyl Tetradecyl, heptadecyl, 15-methylhexadecyl, octadecyl, 1-methylheptadecyl, nonadecyl, eicosyl and 3,7,11,15-tetramethylhexadecyl can be mentioned, preferably having 10 to 10 carbon atoms.
Sixteen straight or branched chain alkyl groups.

The compound (I) of the present invention can be converted into a salt,
Such salts preferably include alkali metal or alkaline earth metal salts such as sodium, potassium or calcium salts; and organic base salts such as triethylamine and trimethylamine salts.

Compound (I) of the present invention has an asymmetric carbon in the molecule,
There are stereoisomers, each of which is in the S or R configuration,
Each of them or a mixture thereof is included in the present invention.

In the compound (I), preferable compounds include: (1) R ¹ and R ⁴ are the same or different and are each a hydrogen atom or a compound represented by the formula-
Compound which is a group having P (O) (OH) ₂ (2) One of R ¹ and R ⁴ is a group having a formula —P (O) (OH) ₂ , and the other is a hydrogen atom or a compound having the formula -P (O)
(OH) compound is a group having the ^₂ (3) R ₂ is a halogen atom, a hydroxyl group or having 10 to 16 carbon aliphatic acyloxy group and optionally also a good number 10 to 16 carbon has an aliphatic acyl (4) a compound in which R ³ is a halogen atom, a hydroxyl group or a C 10 -C 16 alkyl group which may have a C 10 -C 16 aliphatic acyloxy group; ⁵ is a hydrogen atom or the formula _{-COCH 2 CH 2 COOH, -COCH 2} C
Examples of the compound include an acyl group having a carboxy group at a terminal such as a group having H (OH) COOH or -COCH = CH-COOH.

Representative compounds of the present invention include, for example, Table 1A,
The compounds described in Tables 1B, 2A and 2B can be mentioned, but the present invention is not limited to these compounds.

Among the above exemplified compounds, preferred compounds include 1A-12, 15, 39, 43, 44, 67, 69, 70, 71, 92, 93, 94, 96, 97, 9
8,110,111,112,115,116,119,120,121,124,125,130,139,
145,146,147, 1B-1,2,3,4,21,22,23,27,29,33,34,35,43,44,45,50,
52,54,59,60,63,65,68,70,72,74,2A-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,
40,42,43,45,47,48,49,50,51,52,53,54,55,56,57,58,5
9,60,61,62,63,64,65 compounds.

 Further, preferred compounds include 1A-12,39,67,93,120,145,147,1B-3,21,29,33,43,52,54,65,70,72,74,2A-10,54,63, 77,84 and 2B-3,10,14,19,42,43,45,47,48,49,50,58,59,63,65.

The lipid A monosaccharide analog of the present invention can be produced from a known compound, glucosamine (II), as a starting material by the method described below.

[Method A] is a method for producing a compound of the present invention in which a phosphoric acid residue is bonded at the 1-position.

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

In the above formula, R ² and R ³ are as defined above.

R ² ′ and R ^{3 each} have a halogen atom, a hydroxyl group, a hydroxyl group protected by a `` hydroxyl protecting group '' in the definition of R ¹ , R ⁴ or R ⁵ or an aliphatic acyloxy group having 6 to 20 carbon atoms. An optionally substituted aliphatic acyl group having 6 to 20 carbon atoms;
A halogen atom and a hydroxyl group protected by a “hydroxyl protecting group” in the definition of the hydroxyl group, R ¹ , R ⁴ or R ⁵ , or a carbon atom having 6 to 20 carbon atoms having an aliphatic acyloxy group having 6 to 20 carbon atoms.
From 20 to 20 aliphatic acyl groups; or a halogen atom, a hydroxyl group, a hydroxyl group protected by a “hydroxyl protecting group” in the definition of R ¹ , R ⁴ or R ⁵ , or an aliphatic acyloxy group having 6 to 20 carbon atoms. And represents an alkyl group having 6 to 20 carbon atoms which may be possessed.

R ³ ′ is a halogen atom, a hydroxyl group, R ¹ , R ⁴ or
In the definition of R ⁵ , a hydroxyl group protected by a “hydroxyl protecting group” 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, R ¹ A hydroxyl group protected by a “hydroxyl protecting group” in the definition of R ⁴ or R ⁵ , or an aliphatic acyl group having 6 to 20 carbon atoms which may have an aliphatic acyloxy group having 6 to 20 carbon atoms Is shown.

R ³ ″ is a halogen atom, a hydroxyl group, R ¹ , R ⁴ or
It represents a hydroxyl group protected by a “protecting group for hydroxyl group” or an alkyl group having 6 to 20 carbon atoms which may have an aliphatic acyloxy group having 6 to 20 carbon atoms in the definition of R ⁵ .

R ⁶ is, for example, an aliphatic acyl group; an aromatic acyl group; an alkoxycarbonyl group; an alkenyloxycarbonyl group; an aralkyloxycarbonyl group; an amine protecting group such as the silyl group or the aralkyl group. Show.

R ⁷ and R ¹¹ are the same or different and represent the same groups as the “hydroxyl protecting group” in the definition of R ¹ , R ⁴ and R ⁵ . .

R ⁸ and R ⁹ are the same or different and are, 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-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,
A straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms such as 3-dimethylbutyl and 2,3-dimethylbutyl, or an aryl group having 5 to 12 carbon atoms such as phenyl and naphthyl; Can be. The aryl group may have 1 to 4 substituents selected from the following on the ring, and the substituent on the ring includes an amino group; a nitro group; a cyano group; A lower alkyl, a carboxy group which may be substituted with a halogenated lower alkyl or the aralkyl, a carbamoyl group, the halogen atom, the lower alkyl group, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, Halogenated lower alkyl groups such as fluoromethyl, 2,2,2-trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2,2-dibromoethyl and Examples of the aliphatic acyl group include a halogen atom and a halogen lower alkyl group.

R ¹⁰ and R ¹² are the same or different and each represents a protecting group for a phosphoric acid group such as the aryl group or the aralkyl group.

In the first step, glucosamine hydrochloride (II) is converted from trifluoroacetic acid and a condensing agent such as 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, 1,8-diazabicyclo [5.4.0] undec-7
In this step, an amide (III) is produced by reacting an organic base such as ene (DBU) or a trifluoroacetate such as ethyl trifluoroacetate with the above organic base.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent. 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; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide And sulfoxides such as dimethyl sulfoxide.

The reaction is carried out at a temperature of from 0 ° C. to 100 ° C., preferably at room temperature, and the reaction time varies depending mainly on the reaction temperature, the type of the starting compound or the solvent used, but is usually 0.1.
1 hour to 24 hours.

In the second step, the amide compound (III) is converted to a compound of the general formula R
^This is a step of producing a compound (IV) by forming a glycosidic bond with an alcohol having ⁷ OH (eg, methanol, ethanol, benzyl alcohol, allyl alcohol).

As the solvent, a large excess of an alcohol having the general formula R ⁷ OH as a reaction reagent is used.

The acid used is not particularly limited as long as it is generally an acid, but preferably includes mineral acids such as hydrochloric acid and sulfuric acid and organic acids such as p-toluenesulfonic acid. Can also be used.

The reaction is carried out at a temperature of 0 ° C. to 200 ° C., preferably at a reflux temperature, and the reaction time is mainly the reaction temperature,
Although it varies depending on the type of the starting compound or the solvent used, it is usually 0.1 hour to 24 hours.

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

As the reagent used for protecting the diol, usually,
There is no particular limitation as long as it is used for protecting the diol, but preferably, an aldehyde derivative such as benzaldehyde, a ketone derivative such as acetone, 2,2-dimethoxypropane, or a dimethoxy compound such as dimethoxybenzyl Can be mentioned.

The solvent is not particularly limited as long as it does not inhibit the reaction, but is preferably a halogenated hydrocarbon such as methylene chloride or chloroform, an ether such as dioxane or tetrahydrofuran, or a hydrocarbon such as hexane or 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 to be used is not particularly limited as long as it is usually used as an acid.Preferably, an organic acid such as paratoluenesulfonic acid, camphorsulfonic acid, pyridium paratoluenesulfonate or an inorganic acid such as hydrochloric acid is used. Can be mentioned.

The reaction temperature varies depending on the raw material compound and the like used in the acid catalyst, but is usually performed at 0 to 100 ° C., and the reaction time mainly depends on the reaction temperature, the type of the raw material compound or the solvent used. However, it is usually 0.1 to 24 hours.

The fourth step is a step of producing a compound (VI) by removing the R ⁶ group of the compound (V).

When a silyl group is used as the R ⁶ group, it is usually removed by treating 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 preferable. The reaction temperature and reaction time are not particularly limited, but the reaction is usually performed at room temperature for 10 minutes to 18 hours.

When the R ⁶ group is an aliphatic acyl group, an aromatic acyl group or an 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 the other parts of the compound, but is preferably sodium carbonate, an alkali metal carbonate such as potassium carbonate, sodium hydroxide, or potassium hydroxide. This is performed using an alkali metal hydroxide or concentrated ammonia-methanol. The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, and water or water and methanol, ethanol, alcohols such as n-propanol or tetrahydrofuran, ethers such as dioxane, etc. A mixed solvent with such an organic solvent is suitable. The reaction temperature and reaction time vary depending on the starting material and the base used, and are not particularly limited. However, in order to suppress a side reaction, the reaction is usually performed at 0 ° C. to 150 ° C. for 1 to 10 hours.

The removal by reduction is performed using a reducing agent such as sodium borohydride according to a conventional method.

When the R ⁶ group is an aralkyl group or an aralkyloxycarbonyl group, a method of carrying out catalytic reduction at room temperature using a catalyst such as platinum or palladium carbon is preferable.

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

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

The reaction temperature and reaction time vary depending on the type of the starting material and the catalyst, etc., but are usually 0 ° C. to 100 ° C. and 5 minutes to
Implemented for hours.

When R ⁶ is an alkenyloxycarbonyl group,
Usually, the amino group can be eliminated by treating with a base in the same manner as in 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, the removal method using palladium and triphenylphosphine or nickel tetracarbonyl is particularly simple and can be carried out with few side reactions.

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

As a method for acylation, "carboxylic acid wherein with OH, R ^2" formula R ² are the same groups as acyl residues in the definition of the R ² '. Is reacted in the presence of a condensing agent such as dicyclohexylcarbodiimide (DCC), carbonyldiimidazole, or an activated acylating agent R ² ″ X (wherein R ² ″ is as defined above) And X are groups having the general formula OR ² ″; halogen atoms such as chlorine, bromine and iodine; alkylcarbonyloxy groups such as acetoxy and propionyloxy; chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy, trifluoro A halogenated alkylcarbonyloxy group such as acetyloxy, a lower alkoxyalkylcarbonyloxy group such as methoxyacetyloxy, (E)-
Aliphatic acyloxy groups such as unsaturated alkylcarbonyloxy groups such as 2-methyl-2-butenoyloxy; arylcarbonyloxy groups such as benzoyloxy;
Halogenated arylcarbonyloxy groups such as 2-bromobenzoyloxy, 4-chlorobenzoyloxy,
Lower alkylated arylcarbonyloxy groups such as 2,4,6-trimethylbenzoyloxy and 4-toluoyloxy; lower alkoxylated arylcarbonyloxy groups such as 4-anisoyloxy; 4-nitrobenzoyloxy; Aromatic acyloxy groups such as nitrated arylcarbonyloxy groups such as nitrobenzoyloxy;
Trihalogenomethyloxy groups such as trichloromethyloxy; lower alkanesulfonyloxy groups such as methanesulfonyloxy and ethanesulfonyloxy; halogeno lower alkanesulfonyloxy groups such as trifluoromethanesulfonyloxy and pentafluoroethanesulfonyloxy; benzenesulfonyl And a leaving group such as an oxy, arylsulfonyloxy group such as 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 preferably, methylene chloride, chloroform, halogenated hydrocarbons such as carbon tetrachloride, ethers, dioxane, ethers such as tetrahydrofuran, hexane Hydrocarbons such as benzene, aromatic hydrocarbons such as toluene, esters such as ethyl acetate,
Examples include polar solvents such as dimethyl sulfoxide and dimethylformamide.

As the base used, preferably, an organic base can be mentioned, for example, triethylamine, pyridine, DB
U, DBN, N, N-dimethylaniline, N, N-diethylaniline, N, N-dimethylaminopyridine.

The reaction is carried out at a temperature of 0 ° C. to 100 ° C., preferably 20 ° C. to 50 ° C., and the reaction time mainly depends on the reaction temperature,
Although it varies depending on the type of the starting compound or the solvent used, it is usually 0.1 hour to 24 hours.

Alkylation methods include activated alkylating agents
R ² -X '(wherein, R ^2, said R ^2' indicates the same group as the alkyl residues in the definition of, X 'is a halogen atom in the definition of X; aliphatic acyloxy group; an aromatic acyloxy group A lower alkanesulfonyloxy group; a halogeno lower alkanesulfonyloxy group; a leaving group such as 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 preferably, methylene chloride, chloroform, halogenated hydrocarbons such as carbon tetrachloride, ethers, dioxane, ethers such as tetrahydrofuran, hexane Hydrocarbons such as benzene, aromatic hydrocarbons such as toluene, esters such as ethyl acetate,
Examples include polar solvents such as dimethyl sulfoxide and dimethylformamide.

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

The reaction is carried out at a temperature of 0 ° C. to 100 ° C., preferably at room temperature, and the reaction time varies depending mainly on the reaction temperature, the type of the starting compound and the type of the solvent used.
Hours to one day.

The sixth step, the 3-position hydroxyl group of compound (VII), in the same manner as the acylation of the amino group of the fifth step is a step of producing R ³ 'modified compound group (VIII' a).

The seventh step is a step for producing a compound (IX) by removing the protecting group R ^{7 at} the 1-position of the compound (VIII ′).

R ⁷ group is a silyl group, an aralkyloxycarbonyl group,
When it is an aralkyl group, an aliphatic acyl group, an aromatic acyl group, an alkoxycarbonyl group, an alkoxymethyl group or a substituted ethyl group, the R ⁶
It is carried out according to the removal method when the group is the corresponding group.

When the R ⁷ group is a tetrahydropyranyl group, a tetrahydrofuranyl group or the like, it can be usually removed by treating with an acid in a solvent. The acid used is preferably hydrochloric acid, acetic acid-sulfuric acid, paratoluenesulfonic acid or acetic acid.

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

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

When the R ⁷ group is an alkenyloxycarbonyl group, it is usually treated with a base in the same manner as in the removal reaction when the R ⁷ group is an aliphatic acyl group, an aromatic acyl group or an alkoxycarbonyl group. Can be desorbed. In the case of allyloxycarbonyl, the removal method using palladium and triphenylphosphine or nickel tetracarbonyl is particularly simple and can be carried out with few side reactions.

When the R ⁷ group is an allyl group, preferably, in a solvent,
The reaction is carried out in the presence of a catalyst to transfer the double bond to an enol ether type, which can be immediately removed by adding pyridine-iodine-water.

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

Examples of the catalyst used include a palladium catalyst such as palladium chloride and palladium acetate, a rhodium catalyst such as 1,5-cyclooctadiene-bis [methyldiphenylphosphine] rhodium hexafluorophosphate, and rhodium acetate; Double bond transfer agents such as iridium catalysts such as cyclooctadiene-bis [methyldiphenylphosphine] iridium hexafluorophosphate can be mentioned.

The reaction temperature varies depending on the catalyst, the solvent and the like used, but is usually from 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.

The eighth step is a step for producing a compound (X) by phosphorylating the 1-position hydroxyl group of the compound (IX) thus obtained.

Phosphorylation is performed by forming an anion with a base in a solvent and then reacting with a phosphorylating agent.

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

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

As a phosphorylating agent, dibenzyl chlorophosphate,
Reagents commonly used for phosphorylation, such as diphenylchlorophosphate, are used.

The reaction is carried out at a temperature of -78 to 50 ° C, preferably,
−78 ° C. to room temperature, the reaction time depends mainly on the reaction temperature, the type of the starting compound or the solvent used,
Usually 10 minutes to 24 hours.

In the ninth step, the protecting group of compound (X) is removed to produce compound (XI), and if necessary, the protecting group of R ³ 'group is removed.

In principle, the reaction for removing the protecting group of the phosphoric acid residue and the reaction for removing the protecting group of the hydroxyl group vary depending on the type of the protecting group.
The desired removal reactions can be performed sequentially in any order,
Moreover, the operation of removing the protecting group of a hydroxyl group, the protective group of the phosphoric acid residue may also be removed simultaneously, in general, preferable to remove the last protecting group R ¹⁰ groups of the phosphoric acid residue It is. This is because of the ease of handling.

For example, when the R ¹⁰ group is an aralkyl group such as benzyl, protection of the hydroxyl group to R ² and / or R ³ ′ by catalytic reduction at −78 ° C. to 0 ° C. in the presence of a palladium carbon catalyst. including the case where groups are present, any protecting group removal it is possible to at once, R ¹⁰ groups, in the case of aryl groups such as phenyl group, after catalytic reduction in the presence of a palladium carbon catalyst, further It is carried out by performing catalytic reduction under a platinum oxide catalyst.

In some cases (for example, in the case of acetonide), the protecting group in which R ⁸ and R ⁹ groups are a part is removed by silica gel chromatography to remove the protecting group. Alternatively, in a solvent such as an ether such as tetrahydrofuran or dioxane, or an alcohol such as ethanol or methanol, the solvent is removed at 0 to 100 ° C. using dilute hydrochloric acid, dilute sulfuric acid, or hydrated paratoluenesulfonic acid as a catalyst.

When a water-soluble salt of phosphoric acid is obtained, it can be obtained by washing with an inorganic acid once diluted with water such as dilute hydrochloric acid, dissolving in a solvent such as chloroform, and adding a base.

The tenth step is a step of producing a compound (XII) by alkylating the 3-position hydroxyl group of the compound (V) with an R ³ ″ group.

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

In the eleventh step, the protecting group R for the 2-position amino group of the compound (XII) is
Removing ⁶ groups to produce compound (XIII),
This is performed in the same manner as in the fourth step.

In the twelfth step, the 2-position amino group of the compound (XIII) is
Analogously to process, 'modified with groups, compound (VIII' R ² is a step for preparing a).

In addition, the compound (VIII ″) produced can be subjected to the seventh to ninth steps to produce a compound corresponding to the compound (XI).

The thirteenth step is a step of producing a compound (XIV) by removing the hydroxyl groups at the 4- and 6-positions of the compound (VIII) [indicating the compound (VIII ′) or the compound (VIII ″).
This is performed according to the ninth step.

The fourteenth step is a step of preparing compound (XV) by protecting the hydroxyl group at position 6 of compound (XIV) with an R ¹¹ group.

A compound having the general formula R ¹¹ X (wherein R ¹¹ and X have the same meanings as described above, for example, ClCH ₂ OC
_{H 3, ClCH 2 OCH 2 C} 6 H 5, BrCH 2 OCH 2 C 6 H 5, ClCO 2 CH 2 C 6 H 5, Cl
CO ₂ CH ₂ CCl ₃ ) and in a solvent at −50 to 50 ° C. (for example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, ether, dioxane, tetrahydrofuran, etc.). Ethers, hydrocarbons such as hexane, aromatic hydrocarbons such as benzene and toluene, esters such as ethyl acetate,
Polar solvents such as dimethylsulfoxide, dimethylformamide, acetone), bases (eg, DBU, DBN, DMA
P, DABCO, pyridine, triethylamine, aniline, N,
An aqueous solution of N-dimethylaniline, N, N-diethylaniline) or a base (eg, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogencarbonate) in a solvent (eg, acetone, tetrahydrofuran, dioxane) Can be manufactured using.

The fifteenth step is to phosphorylate the 4-hydroxyl group of the compound (XV),
This is a step of producing compound (XVI), which is carried out according to the eighth step.

The sixteenth step is a step of producing the compound (XVII) by removing the protecting group of the compound (XVI). The removal of the protecting groups R ⁷ and R ¹¹ of the hydroxyl group is carried out according to the seventh step. ² 'and / or when over R ³ is a protecting group of the hydroxyl group, removal of the protecting group R ¹² of the protecting groups and phosphoric acid residue is carried out in accordance with the ninth step, in the ninth step As described above, it is preferable to carry out the treatment under such a condition that the protecting group R ¹² of the phosphoric acid residue is removed last.

In the seventeenth step, the protecting group for the hydroxyl group at the 1-position of the compound (XVI) is selectively removed according to the seventh step, and the hydroxyl group at the 1-position is phosphorylated according to the eighth step. When a hydroxyl-protecting group is present on the hydroxyl-protecting group R ¹¹ , R ² ′ and / or R ³ , the protecting group and the protecting group R ¹²
To produce compound (XVIII).

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

The administration form of the compound (I) of the present invention includes, for example,
Examples include oral administration using tablets, capsules, granules, powders, syrups, and the like, and parenteral administration using injections, suppositories, and the like. These formulations contain excipients,
It is manufactured by a known method using additives such as a binder, a disintegrant, a lubricant, a stabilizer, and a flavoring agent. The dosage varies depending on symptoms, age and the like, but it can be usually administered to an adult at a dose of 0.01 to 50 mg / kg body weight once or several times a day.

Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1 (a) N-trifluoroacetylglucosamine 160 g (0.742 mol) of D-(+)-glucosamine hydrochloride was dissolved in 2200 ml of methanol (99.6%), and triethylamine was dissolved.
Add 187.9 g (1.86 mol). Further, 115.9 g of ethyl trifluoroacetate was added dropwise under ice cooling, and the mixture was stirred at room temperature overnight. Concentrate under reduced pressure, benzene 250ml × 2, ethyl acetate 250
ml were sequentially added, concentrated under reduced pressure, and dried sufficiently with a vacuum pump. The crude trifluoroacetyl compound obtained here was advanced to the next step without purification.

1 (b) Allyl 2-deoxy-2-trifluoroacetamide-D-glucopyranoside 1850 ml of a 2% hydrochloric acid-allyl alcohol solution was added to the crude trifluoroacetyl compound obtained in Example 1 (a),
Heated to reflux for minutes. The mixture was cooled to about 50 ° C. with ice water and filtered through celite. The filtrate was concentrated and dried sufficiently with a vacuum pump.

The crude allyl ether obtained here proceeded to the next step without purification.

1 (c) Allyl 2-deoxy-2-trifluoroacetamido-4,6-O-isopropylidene-D-glycopyranoside The crude allyl ether obtained in 1 (b) was converted to N, N-
The residue was dissolved in 740 ml of dimethylformamide, 370 ml of 2,2-dimethoxypropane was added, and 7.5 g of pyridinium p-toluenesulfonate was further added. The mixture was stirred overnight at room temperature.
It concentrated under reduced pressure and diluted with ethyl acetate. The precipitate was removed by filtration, and the filtrate was washed with aqueous sodium hydrogen carbonate, water, and brine. The extract was dried over anhydrous magnesium sulfate, filtered using celite and activated carbon, and concentrated. The residue was not placed on a silica gel column, and cyclohexane: ethyl acetate = 3: 2, and those having an α- and β-ether bond at 8 position were respectively 80.5
g, 77.3 g, obtained by separation and purification. Both α-form and β-form can be used for the subsequent reaction.

[Α-allyl form] Mass spectrum M / Z; 356 [M ⁺ +1], 340,298,282,256,
240,222,211,193,168,126,109,101. [Β-allyl form] Mass spectrum M / Z; 356 [M ⁺⁺ 1], 340,298,280,256,
240,222,211,193,168,155,145,126,114,101.1 1 (d) Allyl 2-deoxy-2-amino-4,6-O-isopropylidene-β-D-glucopyranoside 10 g of the trifluoroacetyl derivative obtained from (c)
After dissolving in 200 ml of ethanol (99.5%), 100 ml of a 1N aqueous sodium hydroxide solution was added, and the mixture was heated under reflux for 4 hours.
It concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with water and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure, and the residual oil was applied to a silica gel column and purified with ethyl acetate.
6.6 g (90.5%) of the desired compound were obtained.

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 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 (as C ₁₂ H ₂₁ NO ₅ = 259.302) 1 (e) Allyl 2-deoxy-2-[(3'-R) -3'-benzyloxymyristoylamide] -4,6-O-isopropylidene-β-D-glucopyranoside 1 (d) 5 g (19.3 mmol) of the obtained compound was dissolved in 150 ml of methylene chloride, 6.8 g of (R) -3-benzyloxymyristic acid was added, further, 4.79 g of N, N'-dicyclohexylcarbodiimide was added, and the mixture was brought to room temperature. And stirred for 1 hour. The mixture was filtered, concentrated under reduced pressure, and diluted with ethyl acetate.
The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate 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 5.33 g (48%) of the desired compound.

Infrared absorption spectrum νmax (KBr) 3510,3280,1643,1550cm- ¹ NMR spectrum _{(270MHz) (CDCl 3) δppm} 0.88 (3H, t, J = 6.9Hz); 1.20-1.41 (18H, m); 1.45 ( Three
H, s); 1.52 (3H, s); 1.56-1.70 (2H, m); 2.43 (1H, d,
d, J = 6.9,15.4Hz); 2.56 (1H, d, d, J = 3.7,15.0Hz); 3.1
9−3.29 (1H, m); 3.46−3.63 (2H, m); 3.75−3.94 (5H, m
m); 4.18-4.24 (1H, m); 4.36 (1H, d, J = 2.6Hz); 4.45
−4.62 (3H, m); 5.12−2.26 (2H, m); 5.70−5.88 (1H,
m); 6.72 (1H, d, J = 5.9 Hz, NH); 7.30-7.37 (5H, m). 1 (f) Allyl 2-deoxy-2 [(3'-R) -3'-benzyloxymyristoylamide] -3-O-[(2 "R
S, 3 "SR) -2" -Fluoro-3 "-(benzyloxycarbonyloxy) myristoyl] -4,6-O-isopropylidene-β-D-glucopyranoside N obtained with 1 (e) 1 g (1.74 mmol) of the acyl compound was dissolved in 80 ml of methylene chloride, and (±) -syn-2-fluoro-3-benzyloxycarbonyloxy myristate 82
8 mg was added, and 359 mg of N, N'-dicyclohexylcarbodiimide and 255 mg of 4-dimethylaminopyridine were sequentially added, followed by stirring at room temperature for 1 hour. The mixture was filtered, concentrated under reduced pressure, and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column and purified with cyclohexane: ethyl acetate 5: 1 to give 1.22 g of the desired compound (7.
3.6%).

Elemental analysis (as _{C 55 H 84 FNO 11 · H} 2 O = 972.286) Infrared absorption spectrum νmax (film) 3290, 1750, 1655 cm-1 NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.66-2.43 (57H, m); 3.12-6.536.517H, m [4.98 (2H,
s)]｝; 7.28 (10H, s). 1 (g) 2-deoxy-2-[(3'R) -3 '-(benzyloxy) myristoylamide] -3-O [(2 "RS, 3" S
R) -2 "-Fluoro-3"-(benzyloxycarbonyloxy) myristoyl] -4,6-O-isopropylidene-D-glucopyranose 380 mg of the compound obtained in 1 (f) were dried in 20 ml. Dissolve in tetrahydrofuran and add 17 mg (5% mol) of 1,5
-Cyclooctadiene-bis [methyldiphenylphosphine] iridium hexafluorophosphate,
The inside of the reaction vessel is replaced with nitrogen and further replaced with hydrogen. After confirming that the color of the solution had changed from red to colorless, it was immediately replaced with nitrogen. After stirring at room temperature for 3 hours, water 2 ml, iodine 200
mg 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 5% aqueous sodium thiosulfate, aqueous sodium hydrogen carbonate, and aqueous sodium chloride. The extract was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was applied to a silica gel chromatography column and purified with cyclohexane: ethyl acetate = 3: 1 to obtain the desired compound 2
80 mg (76.9%) were obtained.

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.53-2.78 (58H, m); 3,48-5.43 ｛11H, m [5.12 (2H,
s)]｝; 6.25 (1H, d, J = 8 Hz); 7.28-7.48 (10H,
m) Elemental analysis (as C ₅₂ H ₈₀ FNO ₁₁ = 914.206) 1 (h) 2-deoxy-2-[(3'R) -3'-hydroxymyristoylamide] -3-O [(2 "RS, 3" SR) -2 "
-Fluoro-3 ″ -hydroxymyristoyl] -α-D
-Glucopyranosyl-1-phosphate Dissolve 550 mg of the compound obtained in 1 (g) in 20 ml of dried tetrahydrofuran, and in a stream of nitrogen, at -78 ° C, 0.4 m of normal butyllithium (1.6 M hexane solution).
l slowly and after 2 minutes 5 dried tetrahydrofuran solution containing 231 mg of dibenzyl phosphorochloridate
ml was added dropwise. Five minutes later, 1 g of 10% palladium carbon was added at the same temperature, and hydrogenated. After 15 minutes, return from -78 ° C to room temperature,
Stir for 3 hours. After filtration, tetrahydrofuran was distilled off under reduced pressure, and the residue was applied to a silica gel chromatography column.
Purification was performed with chloroform: methanol = 5: 1 to obtain the target compound in a yield of 98 mg (22.3%).

Mass spectrum NEG.FAB / MS 728 [M-H] ^- Example 2 (a) Allyl 2-deoxy -2 - [(2'R, 3'S ) and (2'S, 3'R) -2 ' -Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -4,6
-O-isopropylidene-β-D-glucopyranoside 10 g (38.56 mmol) of the compound obtained in 1 (d) was treated with 200 m
l) in methylene chloride, 16.06 g of (±) -syn-2-fluoro-3- (benzyloxycarbonyloxy) myristic acid was added, and 955 g of N, N'M dicyclohexylcarbodiimide was further added, followed by 1 hour at room temperature. Stirred.

The mixture was filtered, concentrated under reduced pressure, and diluted with ethyl acetate. The ethyl acetate layer was washed with sodium hydrogen carbonate and brine,
It was dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column and purified with cyclohexane: ethyl acetate = 2: 1 to obtain the N-acyl compound (2′R, 3 ′S) compound as the target compound And (2'S, 3'R)
The bodies were obtained in yields of 9.6 g (39.03%) and 9.67 g (39.31%), respectively.

[(2′R, 3 ′S) compound] NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (3H, t, J = 6.9 Hz); 1.18-1.43 (18H, m); 1.47 (3
H, s); 1.53 (3H, s); 1.67-1.98 (2H, m); 3.15-3.24
(1H, m); 3.57−3.84 (5H, m); 3.91 (1H, d, d, J = 5.5,1
0.62); 4.02 (1H, d, d, J = 6.2, 12.8 Hz); 4.23-4.30 (1
H, m); 4.39 (1H, d, J = 8.06Hz); 4.94 (1H, d, d, J = 2.2,4
7.6Hz); 5.14-5.28 (5H, m); 6.45 (1H, t, J = 5.4Hz);
7.34−7.41 (5H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 1750,1685,1535 cm −1 [(2 ′S, 3′R) compound] NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (3H, t, J = 6.9 Hz); 1.18-1.43 (18H, m); 1.45 (3
H, s); 1.53 (3H, s); 1.54-2.01 (2H, m); 3.30-3.36
(3H, m); 3.55 (1H, t, J = 9.5Hz); 3.80 (1H, t, J = 10.3H
z); 3.93 (1H, d, d, J = 5.5, 11.0 Hz); 4.01-4.14 (2H,
m); 4.27 (1H, d, d, J = 5.5,18.3Hz); 4.87 (1H, d, J = 8.4
Hz); 4.91 (1H, d, d, J = 2.2, 48.0 Hz); 5.09-5.3 (5H,
m); 5.78-5.93 (1H, m); 6.60 (1H, t, J = 5.1Hz); 7.26
−7.38 (5H, m). Elemental analysis (as C ₃₄ H ₅₂ FNO ₉ = 637.786) Infrared absorption spectrum νmax (CHCl ₃ ) 1750,1685,1535cm-12 (b) Allyl 2-deoxy-2-[(2′R, 3 ′S) -2 ′
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″ -benzyloxymyristoyl] -4,6-O-isopropylidene-β-D-glucopyranoside 3.5 g (5.4 ′) of the (2′R, 3 ′S) compound obtained with 2 (a)
9 mmol) was dissolved in 150 ml of methylene chloride, and 1.93 g of (R) -3-benzyloxymyristate was added thereto. Further, 0.7 g of 4-dimethylaminopyridine and 1.36 g of N, N-
Dicyclohexylcarbodiimide was added, and the mixture was stirred at room temperature for 1 hour. The mixture 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.
Purification was performed with ethyl acetate = 5: 1.
%).

NMR spectrum _{(270MHz) (CDCl 3) δppm} 0.88 (6H, t, J = 6.6Hz); 1.25-1.73 (46H, m); 2.42-2.
61 (2H, m); 3.35-3.42 (1H, m); 3.56-4.08 (6H, m);
4.21-4.28 (1H, m); 4.40-4.98 (4H, m); 5.07-5.36
(6H, m); 5.72-5.86 (1H, m); 6.44-6.48 (1H, m); 7.1
4-7.35 (10H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 1743,1695,1530cm-12 (c) 2-deoxy-2-[(2′R, 3 ′S) -2′-fluoro-3 ′-(benzyloxycarbonyloxy ) Myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -4,6-O-isopropylidene-D-glucopyranose 2 (b) By treating in the same manner as in (g), the target compound was obtained in a yield of 2.69 g (79.3%).

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (6H, t, J = 6.2 Hz); 1.23-1.73 (46H, m); 2.42-2.
54 (3H, m); 3.60-4.02 (6H, m); 4.42-5.27 (9H, m);
7.16-7.46 (10H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 1745,1685,1535cm-12 (d) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-hydroxymyristoylamide]- 3-O-
[(3 "R) -3" -hydroxymyristoyl] -α-
D-Glucopyranosyl-1-phosphate The compound obtained with 2 (c) was treated in the same manner as 1 (h) to give the desired compound in 91 mg (11%) yield.

Mass spectrum NEG.FAB / MS 728 [M-H] ^- Example 3 (a) Allyl 2-deoxy -2 - [(2'S, 3'R ) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 "-benzyloxycarbonyloxymyristoyl]
3.5 g of the (2 ′S, 3′R) compound obtained with -4,6-O-isopropylidene-β-D-glucopyranoside 3 (a)
By treating in the same manner as in Example 2 (b), 2.7 g of the target compound was obtained.
(49.3%).

3 (b) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)- 3 "-(benzyloxycarbonyloxy) myristoyl] -4,6-
O-Isopropylidene-D-glucopyranose The compound obtained in 3 (a) was treated in the same manner as in 1 (g) to obtain 1.75 g (67.5%) of the target compound.

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.81-2.34 (52H, m); 2.47-2.78 (2H, m); 3.00 (1H, b,
OH); 3.45-5.51 {14H, m [including 5.12 (4H, s)]}; 6.6
5 (1H, b, NH); 7.35 (10H, s). Infrared absorption spectrum νmax (CHCl ₃ ) 1745,1670,1545cm-13 (c) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-hydroxymyristoylamide]- 3-O-
[(3 "R) -3" -hydroxymyristoyl] -α-
D-Glucopyranosyl phosphate The compound obtained with 3 (b) was treated in the same manner as 1 (h) to give 190 mg (29.3%) of the target compound.

Example 4 (a) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(benzyloxycarbonyloxy) myristoyl] -4,6-O-isopropylidene-β-D-glucopyranoside The (2′R, 3 ′S) compound obtained in 2 (a) was The same treatment as in Example 3 (a) was carried out to obtain 6.1 g (77.9 g) of the target compound.
%).

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.86-2.23 (52H, m); 2.45-2.84 (2H, m); 3.17-6.30
{19H, m [including 5.12 (4H, s)]}; 6.58 (1H, b, NH); 7.
33 (10H, s). Infrared absorption spectrum νmax (KBr) 1745,1671,1545cm-14 (b) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(benzyloxycarbonyloxy) myristoyl] -β-D-glucopyranoside 5 g (5.24 mmol) of the compound obtained in 4 (a) was added to 50 ml of
It was suspended in 80% acetic acid and stirred at 50 ° C. for 30 minutes. The acetic acid was distilled off under reduced pressure, the residue was applied to a silica gel column, and purified with cyclohexane: ethyl acetate = 1: 1 to obtain the desired compound 4.5.
Obtained in a yield of 5 g (94.8%).

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (6H, t, J = 6.9 Hz); 1.08-1.84 (40H, m); 2.47 (1
H, d, d, J = 8.1,15.0Hz); 2.58 (1H, d, d, J = 3.7,15.0H
z); 3.26 (1H, b, OH); 3.40-3.45 (1H, m); 3.61 (1H, t,
J = 9.2Hz); 3.75-3.94 (3H, m); 4.00-4.31 (2H, m);
4.63 (1H, d, J = 8.4Hz); 4.82-5.28 (11H, m); 5.75-5.
88 (1H, m); 6.00 (1H, d, d, J = 4.4,8.4Hz); 7.33-7.38
(10H, m). Elemental analysis (as C ₅₃ H ₈₀ FNO ₁₃ = 958.215) Infrared absorption spectrum νmax (CHCl ₃ ) 1745,1695,1535cm-14 (c) Allyl 2-deoxy-2-[(2′R, 3 ′S) -2 ′
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(benzyloxycarbonyloxy) myristoyl] -6-O-benzyloxycarbonyl-β-D-glucopyranoside 4.3 g (4.5 mmol) of the compound obtained in 4 (b) was dissolved in 100 ml of methylene chloride. , 4-dimethylaminopyridine 822
916 mg of benzyloxychloroformate was added dropwise, and the mixture was stirred at room temperature for 1 hour. Concentrate under reduced pressure,
It was diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the 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 desired compound in a yield of 2.43 g (49.6%).

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.64-1.89 (46H, m); 2.37-2.64 (2H, m); 3.09-6.20
{22H, m [including 5.09 (4H, s), 5.13 (2H, s)]}; 6.49
(1H, b); 7.32 (15H, s). Infrared absorption spectrum νmax (CHCl ₃ ) 1745,1695,1533cm-14 (d) Allyl 2-deoxy-2-[(2′R, 3 ′S) -2 ′
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(benzyloxycarbonyloxy) myristoyl] -4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-β-D-glucopyranoside 2.2 g of the compound obtained with 4 (c) ( 2.01 mmol) was dissolved in 30 ml of methylene chloride, 1.47 g of 4-dimethylaminopyridine was added, 1.62 g of diphenylchlorophosphate was added dropwise, and the mixture was stirred at room temperature for 1 hour.
It was diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure.
The residue was applied to a silica gel column and purified with cyclohexane: ethyl acetate = 3: 1 to obtain 2.65 g (99.3%) of the target compound.

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.64-2.05 (46H, m); 2.25-2.51 (2H, m); 3.00-6.15
{21H, m [including 5.08 (6H, s)]}; 6.63 (1H, b); 7.18
−7.33 (25H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 1747,1690,1590,1530cm-14 (e) 2-deoxy-2-[(2′R, 3 ′S) -2′-fluoro-3 ′-(benzyloxy Carbonyloxy) myristoylamide] -3-O-[(3 "R) -3"-(benzyloxycarbonyloxy) myristoyl] -4-O
-Diphenoxyphosphinyl-6-O-benzyloxycarbonyl-D-glucopyranose The compound obtained in 4 (d) was treated in the same manner as 1 (g) to give 1.6 g (69.3%) of the desired compound. I got it.

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (6H, t, J = 6.2 Hz); 1.13-1.71 (40H, m); 2.37 (1
H, dd, J = 7.33,17.22Hz); 2.55 (1H, dd, J = 5.13,17.22H)
z); 3.61 (1H, b); 3.83-3.90 (1H, m); 4.16-4.37 (3
H, m); 4.64-4.81 (2H, m); 4.96-5.28 (9H, m); 5.56
(1H, dd, J = 9.2,11.0Hz); 6.84 (1H, dd, J = 3.3,7.7H
z); 7.09-7.37 (25H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 1743,1685,1590cm-14 (f) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-hydroxymyristoylamide]- 3-O-
[(3 "R) -3" -hydroxymyristol] -D-glucopyranosyl-4-phosphate 1.3 g (1.01 mmol) of the compound obtained in 4 (e) is dissolved in 30 ml of tetrahydrofuran and 1 g of 10% Palladium carbon was added, and the mixture was catalytically reduced at room temperature for 3 hours. Filtered,
200 mg of platinum oxide was added to the filtrate, and catalytic reduction was performed again at room temperature for 2 hours. Filtration, distilling off tetrahydrofuran under reduced pressure,
The residue was applied to a silica gel column and purified with chloroform: methanol = 9: 1 and chloroform: methanol = 5: 1 to obtain 490 mg (66.3%) of the target compound in a yield.

Infrared absorption spectrum νmax (KBr) 1710,1660cm-1 Mass spectrum NEG, FAB / MS M / Z728 [M-H] ^- Example 5 (a) Allyl 2-deoxy -2 - [(2'S, 3 ' R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″ -benzyloxymyristoyl] -4,6-O-isopropylidene-β-D-glucopyranoside 4.5 g (7.06 mmol) of the (2S, 3R) compound obtained with 2 (a)
l) was dissolved in 100 ml of tetrahydrofuran, 857 ml of triethylamine was added, and 2.86 g of 3-benzyloxymyristate chloride was further added dropwise, followed by stirring at room temperature for 1 hour. It concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column and purified with cyclohexane: ethyl acetate = 5: 1 to obtain the desired compound.
Obtained in a yield of 5.0 g (75.7%).

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.65-2.08 {52H, m [including 1.43 (3H, s)]}; 2.43-2.
72 (2H, m); 3.05-6.21 ｛19H, m [4.48 (2H, s); 5.12 (2
H, s)]｝; 6.31-6.67 (1H, m); 7.28 (5H, s); 7.
30 (5H, s). Infrared absorption spectrum νmax (KBr) 1745,1670,1545,1268,1089cm-15 (b) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″ -Benzyloxymyristoyl] -β-D-glucopyranoside The compound obtained in 5 (a) was treated in the same manner as in 4 (b) to obtain 4.14 g (96%) of the target compound. .

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.62-2.18 (46H, m); 2.32-2.91 (4H, m); 3.20-4.25
(8H, m); 4.28-4.71 {3H, m [including 4.48, (2H, s)]}; 4.86-6.19 (8H, m); 6.45-6.85 (1H, m); 7.28
(5H, s); 7.31 (5H, s). Infrared absorption spectrum νmax (KBr) 1742,1669,1578,1271cm-15 (c) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″ -benzyloxymyristoyl] -6-O-benzyloxycarbonyl-β-D-glucopyranoside The compound obtained in 5 (b) was treated in the same manner as in 4 (c) to give 2.85 of the desired compound. g (65.4%).

NMR spectrum _{(60MHz) (CDCl 3) δppm} 0.85-2.08 (46H, m); 2.41-2.64 (2H, m); 3.00 (1H,
b); 3.48-6.08 {21H, m [including 4.45 (2H, s), 5.15 (4H, s)]}; 6.18-6.72 (1H, m); 7.26-7.56 (15H, m). Infrared absorption spectrum νmax (KBr) 1750,1727,1676,1548cm-15 (d) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″ -benzyloxymyristoyl] -4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-β-D-glucopyranoside The compound obtained with 5 (c) is referred to as 4 (d). After the same treatment, the target compound was obtained in a yield of 3.16 g (99.5%).

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.72-1.87 (46H, m); 2.26-2.49 (2H, m); 3.45-6.05
{21H, m [including 4.30 (2H, s), 5.05 (4H, s)]}; 6.18
−6.50 (1H, m); 6.89−7.49 (25H, m). Infrared absorption spectrum νmax (KBr) 1743,1679,1541,1494cm-15 (e) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3 '-(benzyloxycarbonyl Oxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-D-glucopyranose 5 (d The compound obtained in (1) was treated in the same manner as in 1 (g) to give 1.8 g (66.4%) of the desired compound.

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.66-2.01 (46H, m); 2.16-2.56 (2H, m); 2.89 (1H, d,
J = 5Hz); 3.38-5.71 ｛16H, m [432 (2H, s), 5.10 (4H,
s)]｝; 6.45 to 6.81 (1H, m); 7.08 to 7.45 (25H,
m). Infrared absorption spectrum νmax (KBr) 1747,1685,1590cm-15 (f) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-hydroxymyristoylamide] -3 -O-
[(3 "R) -3" -hydroxymyristoyl] -4-
O-Diphenoxyphosphinyl-D-glucopyranose 880 mg (0.6 mmol) of the compound obtained in 5 (e) was dissolved in 30 ml of tetrahydrofuran, 1 g of 10% palladium carbon was added, and the mixture was subjected to catalytic reduction at room temperature for 2 hours. did. After filtration, tetrahydrofuran was distilled off under reduced pressure, the residue was applied to a silica gel column, and purified with ethyl acetate to obtain 340 mg of the desired compound.
(56.2%).

Elemental analysis (as C ₄₆ H ₇₃ FNO ₁₂ P = 882.057) 5 (g) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-hydroxymyristoylamide] -3-O-
[(3 "R) -3" -hydroxymyristoyl] -D-
Glucopyranosyl-4-phosphate Compound (490 mg, 0.56 mmol) obtained in 5 (f) was dissolved in tetrahydrofuran (30 ml), and platinum oxide (80 mg) was added, followed by catalytic reduction at room temperature for 3 hours. After filtration, the tetrahydrofuran was distilled off under reduced pressure to obtain 380 mg (93.7%) of the target compound.

Elemental analysis (as C ₃₄ H ₆₅ FNO ₁₂ P = 729.861) Mass spectrum NFG, FAB / MS M / Z728 [M-H] ¹ 502. Example 6 (a) Allyl 2-deoxy -2 - [(2'R, 3'S ) and (2'S, 3'R ) -2'-Fluoro-3 '-(myristoyloxy) myristoylamide] -4,6-O-isopropylidene-β-D-glucopyranoside 5.18 g (20 mmol) of the compound obtained in 1 (d) was chlorided. Dissolve in 150 ml of methylene, add 9.93 g of (±) -syn-2-fluoro-3-myristoyloxymyristic acid, further add N,
4.95 g of N'-dicyclohexylcarbodiimide was added, and the mixture was stirred at room temperature for 1 hour. Filter, concentrate under reduced pressure and dilute with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, the residue was subjected to silica gel chromatography, and purified with cyclohexane: ethyl acetate = 3: 1 to give the N-acyl compound (2′R, 3 ′) as the target compound.
5.65 g (39.6 g) of the (S) form and the (2 ′S, 3′R) form, respectively.
%), 5.55 g (38.9%).

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm [(2′R, 3 ′S) compound] 0.88 (6H, t, J = 6.9 Hz); 1.20-1.38 (38H, m); 1.44 (3
H, s); 1.52 (3H, s); 1.60-1.84 (5H, m); 2.30 (2H,
t); 3.23-3.33 (1H, m); 3.58-3.85 (4H, m); 3.93 (1
H, d, d, J = 5.5,10.6Hz); 4.07 (1H, d, d, J = 6.2,12.8H
z); 4.30-4.37 (1H, m); 4.76 (1H, d, J = 7.7Hz); 4.93
(1H, d, d, J = 2.9,48.0Hz); 5.20-5.36 (3H, m); 5.79-
5.94 (1H, m); 6.44 (1H, t, J = 5.5Hz). Infrared absorption spectrum νmax (CHCl ₃ ) 1735,1680,1535 cm -1 [(2'S, 3'R) compound] 0.88 (6H, t, J = 6.9Hz); 1.20-1.38 (38H, m); 1.45 (3
H, s); 1.52 (3H, s); 1.56-1.76 (5H, m); 2.29 (2H,
t); 3.30-3.41 (2H, m); 3.57 (1H, t, J = 9.2Hz); 3.80
(1H, t, J = 10.6Hz); 3.93 (1H, d, d, J = 5.5,11.0Hz); 4.
05-4.16 (2H, m); 4.29-4.36 (1H, m); 4.77 (1H, d, J =
8.1 Hz); 4.89 (1H, d, d, J = 2.2, 48.0 Hz); 5.20-5.34 (3
H, m); 5.80-5.89 (1H, m); 6.52 (1H, t, J = 5.5Hz). Infrared absorption spectrum νmax (CHCl ₃ ) 1735,1680,1535cm-16 (b) Allyl 2-deoxy-2-[(2′R, 3 ′S) -2 ′
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-myristoyl-4,6-O-isopropylidene-β-D-glucopyranoside Compound (2′R , 3'S) 2g (2.8
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 stirred at room temperature for 1 hour. It was concentrated, diluted with ethyl acetate, washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column and purified with cyclohexane: ethyl acetate = 5: 1 to obtain the desired compound.
Obtained in a yield of 1.35 g (52.1%).

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.6 Hz); 1.13-1.67 ｛70 H, m [1.36 (3H,
s), 1.46 (3H, s)]｝; 2.25-2.35 (4H, m); 3.32
−3.41 (1H, m); 3.66−3.85 (3H, m); 3.95 (1H, d, d, J =
5.5, 10.6 Hz); 4.05 (1H, d, d, J = 6.2, 12.8 Hz); 4.26-4.
34 (1H, m); 4.74-4.93 (2H, m); 5.16-5.29 (4H, m);
5.75-5.89 (1H, m); 6.34 (1H, d, d, J = 4.4,8.8 Hz). Elemental analysis (as C ₅₄ H ₉₈ FNO ₉ = 924.374) Infrared absorption spectrum νmax (CHCl ₃ ) 1740,1695cm-1 Mass spectrum M / Z924 (M ⁺⁺ 1), 909,883,867,737,724,655,638,610,5
26,513,452. 6 (c) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-β-D-glucopyranoside The compound obtained in 6 (a) was treated in the same manner as in 4 (b), The compound was obtained in a yield of 2 g (80.4%).

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.66-1.91 (74H, m); 2.09-2.55 (4H, m); 2.87-6.16
(15H, m); 6.54 (1H, m). Infrared absorption spectrum νmax (KBr) 1739,1668,1553,1468,1175cm-16 (d) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-6-O-benzyloxycarbonyl-β-D-glucopyranoside 1.9 g (2.15 mmol) of the compound obtained in 6 (c) was obtained. Was dissolved in 20 ml of methylene chloride, 550 mg of benzyloxychloroformate was added, and 327 mg of triethylamine was further added, followed by stirring at room temperature for 5 hours. It was concentrated and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column, and cyclohexane: ethyl acetate = 3: 1.
The title compound was obtained in a yield of 660 mg (30.2%).

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.9 Hz); 1.25-1.65 (66H, m); 2.25-2.
36 (4H, m); 2.82 (1H, s); 3.59-3.66 (2H, m); 4.03 (1
H, d, d, J = 6.2,12.8Hz); 4.27 (1H, d, d, J = 5.1,12.8H)
z); 4.42-4.52 (1H, m); 4.81 (1H, d, d, J = 3.7,47.6H
z); 4.84 (1H, d, J = 8.1Hz); 5.14-5.27 (6H, m); 5.76
−5.89 (1H, m); 6.37 (1H, d, d, J = 4.4,8.1Hz); 7.34−
7.40 (5H, m). Infrared absorption spectrum νmax (KBr) 1737,1673,1550,1285cm-16 (e) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-β
-D-Glucopyranoside 600 mg (0.589 mmol) of the compound obtained in 6 (d) was dissolved in 20 ml of methylene chloride, 474.8 mg of diphenylchlorophosphate was added, and 62.6 mg of triethylamine was further added. Stirred. It concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column, and cyclohexane: ethyl acetate = 5:
Purification was performed in 1 to give the desired compound in a yield of 600 mg (81.4%).

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.9 Hz); 1.05-1.73 (64H, m); 2.11-2.
3. (4H, m); 3.46-3.56 (1H, m); 3.77-3.82 (1H, m); 4.
03 (1H, 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); 5.64-5.87 (2H, m
m); 6.37 (1H, d, d, J = 4.4, 7.7 Hz); 7.11-7.34 (15H,
m). As Elemental Analysis _{C 71 H 109 FNO 14 P =} 1250.618) Infrared absorption spectrum νmax (CHCl ₃ ) 1743,1690cm-16 (f) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-D-glucopyranose The compound obtained in 6 (e) was treated in the same manner as 1 (g),
The target compound was obtained in a yield of 490 mg (84.3%).

NMR spectrum _{(270MHz) (CDCl 3) δppm} 0.88 (9H, t, J = 7.0Hz); 1.11-1.66 (64H, m); 2.11-2.
29 (4H, m); 3.36 (1H, s); 4.13-4.39 (4H, m); 4.71-
5.56 (7H, m); 6.70 (1H, d, d, J = 3.3,8.1Hz); 7.11-7.3
5 (15H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 1751,1711,1658 cm-16 (g) 2-deoxy-2-[(2′R, 3 ′S) -2′-fluoro-3′-myristoyloxymyristoylamide] −
3-O-myristoyl-4-O-diphenoxyphosphinyl-D-glucopyranose The compound obtained in 6 (f) was treated in the same manner as in 5 (f) to give the desired compound in a yield of 270 mg (75.9%). I got it.

Elemental analysis (as C ₆₀ H ₉₉ FNO ₁₂ P = 1076.419) Infrared absorption spectrum νmax (CHCl ₃ ) 1735,1685cm-16 (h) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-D-glucopyranosyl-4-phosphate The compound obtained with 6 (g) is treated in the same way as 5 (g),
The target compound was obtained in a yield of 190 mg (96.2%).

Mass spectrum NEG, FAB / MS M / Z922 [M-H] ^- Example 7 (a) Allyl 2-deoxy -2 - [(2'S, 3'R ) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-4,6-O-isopropylidene-β-D-glucopyranoside 6 (a) (2 ′S, 3 ′ R) 2.9g (4.06mmo)
l) is dissolved in methylene chloride (30 ml), and myristic acid (1.02 g) is dissolved.
And N, N'-dicyclohexylcarbodiimide 1
g was added and the mixture was stirred at room temperature for 1 hour, but the reaction had not progressed.
The mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure, diluted with ethyl acetate, and the ethyl acetate layer was washed with aqueous sodium hydrogen carbonate,
The extract was washed with 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 quantitatively obtain the target compound.

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.66-2.01 (79H, m); 2.05-2.61 (4H, m); 3.30-6.23
(14H, m); 6.85 (1H, m). Infrared absorption spectrum νmax (KBr) 1741,1666,1544,1468cm-17 (b) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-β-D-glucopyranoside The compound obtained in 7 (a) was treated in the same manner as in 4 (b) to give 3.08 g of the desired compound (84.7%).

Infrared absorption spectrum νmax (KBr) 1736,1671,1553,1467cm-17 (c) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-6-O-benzyloxymethyl-β-D-glucopyranoside 2.7 g (3.05 mmol) of the compound obtained in 7 (b) was obtained. , Dissolved in 50 ml of methylene chloride and benzyl chloromethyl ether
0.525 g was added, and 0.355 g of tetramethyl urea was further added.
Heated to reflux for an hour. The 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 2.08 g (67.8%) of the desired compound.

NMR spectrum (270 MHz) (CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.9 Hz); 1.20-1.73 (65H, m); 2.24-2.
37 (4H, m); 3.47-3.51 (1H, m); 3.74 (1H, t, J = 9.5H
z); 3.89-4.11 (4H, m); 4.26-4.33 (1H, m); 4.59 (1
H, d, J = 8.4Hz); 4.63 (2H, s); 4.79 (1H, d, d, J = 4.3,4
8.4Hz); 4.81 (2H, s); 5.03 (1H, d, d, J = 9.2,10.6Hz);
5.15-5.30 (3H, m); 5.80-5.88 (1H, m); 6.36 (1H, d,
d, J = 4.4, 9.2 Hz); 7.29-7.36 (5H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 3430,1738,1695cm-1 Mass spectrum M / Z986,928,834,775,717,596,509,456,383,354,298,2
85,268.

7 (d) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxymethyl-β-D
-Glucopyranoside The compound obtained in 7 (c) was treated in the same manner as in 6 (e) to quantitatively obtain the target compound.

NMR spectrum _{(270MHz) (CDCl 3) δppm} 0.88 (9H, t, J = 6.9Hz); 1.10-1.68 (65H, m); 2.08-2.
31 (3H, m); 3.65-3.69 (2H, m); 3.78-3.84 (1H, m);
4.03-4.11 (2H, m); 4.25-4.32 (1H, m); 4.50-4.85
(7H, m); 5.15-5.39 (4H, m); 5.76-5.83 (1H, m); 6.3
8 (1H, d, J = 4.8, 9.2Hz); 7.13-7.44 (15H, m). Infrared absorption spectrum νmax (CHCl ₃ ) 3430,1740,1695cm-1 Mass spectrum M / Z1014,994,758,670,580,440,322,2688.7 (e) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro- 3'-myristoyloxymyristoylamide]-
3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxymethyl-D-glucopyranose The compound obtained in 7 (d) was treated in the same manner as 1 (g),
The target compound was obtained in a yield of 1.58 g (71%).

NMR spectrum (60 MHz) (CDCl ₃ ) δ ppm 0.63-2.42 (77H, m); 3.55-5.78 ｛14, m [4.54 (2H,
s), 4.66 (2H, s)]｝; 6.70 (1H, m); 7.00-7.53
(15H, m). 7 (f) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-4-O-diphenoxyphosphinyl-D-glucopyranose 1.44 g (1.2 mmol) of the compound obtained in 7 (e) was dissolved in 30 ml of methanol, and 1 g of 10% palladium carbon was added.
The catalytic reduction was carried out 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 desired compound in a yield of 715 mg (55.2%).

Infrared absorption spectrum νmax (CHCl ₃ ) 3440,1740,1690cm-1 Elemental analysis (as C ₆₀ H ₉₉ FNO ₁₂ P = 1076.419) 7 (g) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-D-glucopyranosyl-4-phosphate The compound obtained with 7 (f) was treated in the same manner as 5 (g) to give the desired compound in 420 mg (89%) yield.

Mass spectrum NEG, FAB / MS M / Z922 [M-H] ^- Example 8 (a) Allyl 2-deoxy-2-trifluoroacetamido -3-O - [(3'RS) -3'- benzyloxy deca Nyl] -4,6-O-isopropylidene-α-D-glucopyranoside 18 g of allyl 2-trifluoroacetamide-α-D-glucopyranoside obtained in 1 (c), (±) -3-
16.5 g of benzyloxy-1-mesyloxydecane was dissolved in 110 ml of dry dimethylformamide, and 55 ml of this was dissolved under ice cooling.
% Sodium hydride was added little by little, and then stirred at room temperature for 3 hours. The reaction solution was diluted with 300 ml of ethyl acetate, and neutralized by adding 10.3 g of acetic acid at 15 to 20 ° C. Next, the extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 30 g of an oily substance of the title compound. This is obtained by silica gel column chromatography (cyclohexane: ethyl acetate =
9: 1), but used directly in the next deprotection reaction.

8 (b) allyl 2-deoxy-2-amino-3-O-[(3 ′
RS) -3'-benzyloxydecanyl] -4,6-O-isopropylidene-α-D-glucopyranoside 30 g of the 2-trifluoroacetylamino compound obtained in 8 (a) was dissolved in 550 ml of ethanol, 275 ml of a 1 N aqueous sodium hydroxide solution was added thereto, and the mixture was stirred and refluxed for 2 hours. The reaction was concentrated and diluted with 700 ml of ethyl acetate,
The extract was washed with water and saturated saline, and dried over anhydrous magnesium sulfate. Next, the residue was concentrated to dryness and purified through a silica gel column (cyclohexane: ethyl acetate = 3: 2) 30 times the amount of the residue to obtain 12.3 g of the title compound as an oil.

NMR spectrum (CDCl ₃ ): δ ppm 0.7-2.1 (23H, m); 2.5-2.9 (1H, m); 3.0-4.2 (10H,
m); 4.5 (2H, s); 4.7-6.3 (4H, m); 7.3 (5H, s). 8 (c) Allyl 2-deoxy-2-[(3'R) -3'-benzyloxymyristoylamide] -3-O-[(3 "R
S) -3 "-Benzyloxydecanyl] -4,6-O-isopropylidene-.alpha.-D-glucopyranoside allyl 2-deoxy-2-[(3'R) -3'-benzyloxymyristoylamide ] -3-O-[(3 ″ R
S) -3 "-Benzyloxydecanyl] -4,6-O-isopropylidene-α-D-glucopyranoside 12.3 g of the 2-amino compound obtained in 8 (b), (±)
9.8 g of -3-benzyloxymyristic acid was dissolved in 150 ml of dry methylene chloride, and 6.5 g of N, N'-dicyclohexylcarbodiimide was added thereto at room temperature, followed by stirring at room temperature for 2 hours. The reaction solution was filtered to remove the precipitate, and then methylene chloride was distilled off under reduced pressure. Next, 100
Purification through a chromatography column (cyclohexane: ethyl acetate = 4: 1) using twice the amount of silica gel gave 7.5 g of the title (R) compound and 7.8 g of the (S) compound.

[(R) compound] NMR spectrum (CDCl ₃ ): δ ppm 0.70 to 2.05 (46H, m); 2.2 to 2.5 (2H, m); 3.2 to 6.6 (26
H, m); 7.3 (10H, s). Infrared absorption spectrum ν _max cm-1 (CHCl ₃ ); 1662. Mass spectrum (m / e): 822 (M ⁺⁺ 1), 806,730,672,609,568,516. [(S) compound] Infrared absorption spectrum ν _max cm-1 (CHCl 3) ₃ ); 1661 Mass spectrum (m / e): 822 (M ⁺⁺ 1). 8 (d) 2-Deoxy-2-[(3'R) -3 '-(benzyloxy) myristoylamide] -3-O-[(3 "RS)-
3 "-benzyloxydecanyl] -4,6-O-isopropylidene-D-glucopyranose 3.7 g of the (R) -2-acyl compound obtained in 8 (c) was dissolved in 170 ml of dry tetrahydrofuran, and iridium complex (1,5-cyclooctadiene-bis [methyldiphenylphosphine] iridium hexafluorophosphate) was added thereto. 0.26 g was added. The air in the reaction vessel was sucked by an aspirator and then replaced with nitrogen. Next, this nitrogen was sucked by 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 atmosphere was replaced with nitrogen, and the mixture was stirred at room temperature for 3 hours.
17 ml of water, 2.3 g of iodine and 1.4 g of pyridine were added to the reaction solution, and after stirring at room temperature for 15 minutes, tetrahydrofuran was evaporated under reduced pressure. The residue was diluted with ethyl acetate, washed with a 5% aqueous solution of sodium sulfite, a saturated aqueous solution of sodium hydrogen carbonate, and a saturated aqueous solution of sodium chloride in that order, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by 50-fold silica gel column chromatography (cyclohexane: ethyl acetate = 7: 3) to obtain 3.2 g of the title compound as an oil.

NMR spectrum (CDCl ₃ ): δ ppm 0.7-1.9 (46H, m); 2.2-2.55 (2H, m); 3.0-4.0 (11H,
m); 4.45-4.55 (4H, m); 5.0-5.15 (1H, m); 6.4 (1H,
d, J = 8.5 Hz); 7.34 (10H, s). Infrared absorption spectrum ν _max cm-1 (liquid film); 3300,1735,1641,1652. Mass spectrum (m / e): 609,551,519,502,488,417.8 (e) 2-deoxy-2-[(3′R) -3 '-Hydroxymyristoylamide] -3-O-[(3 "RS) -3" -hydroxydecanyl] -α-D-glucopyranomyl-1-
Phosphate A solution of the compound obtained in 8 (d) (1.17 g, 1.5 mmol) in dry tetrahydrofuran (20 ml) was cooled to -78 ° C under a nitrogen stream, and stirred, while stirring, 1.02 ml (1.65 mmol) of a 1.6 M hexane solution of n-butyllithium. After 2 minutes, dibenzylphosphorochloridate [ClP (O) (OBn) ₂ , 580 mg, 1.9 mg
5 mmol, 1.3 equivalents] in 10 ml of tetrahydrofuran. After stirring at −78 ° C. for 10 minutes, 4.0 g of 10% palladium on carbon was added, and the mixture was reduced in a hydrogen stream at −60 ° C. for 30 minutes, and the cooling bath was removed. The palladium carbon was removed by filtration, washed with methanol, and the solution was concentrated. Next, silica gel column chromatography was performed. The elementary reaction remains acetonide-free, but acetonide is removed by silica gel column chromatography. All was eluted with chloroform-methanol (1: 1) and then re-chromatographed on a 30 g silica gel column. 1%
Elution with a chloroform solution of methanol yielded 402 mg (41.7 mg).
%) Of the desired product.

NMR spectrum (CD ₃ COOD): 270 MHz δ ppm 0.90 (6H, m); 1.14-1.83 (34H, m); 2.54 (2H, m); 3.45
-4.40 (10H, m); 5.76 (1H, m). FAB mass spectrum (M / Z): 640 [MN] ⁻ .8 (f) Triethylamine salt of phosphoric acid compound When it is necessary to obtain a water-soluble triethylamine salt of the phosphoric acid compound obtained in 8 (e), Do the following:

30 mg of phosphoric acid was suspended in 8 ml of 0.1 N hydrochloric acid, and 30 ml of chloroform-methanol (1: 2) was further added thereto, followed by ultrasonication to dissolve. When 10 ml of chloroform and 10 ml of 0.1 N hydrochloric acid were added to this solution, the solution was separated into two layers, and the chloroform layer was separated. Chloroform was removed under reduced pressure and dissolved in 0.1% triethylamine water, and this aqueous solution was used as a sample for activity measurement.

Example 9 (a) 2-deoxy-2-[(3'S) -3 '-(benzyloxy) myristoylamide] -3-O-[(3 "RS)-
3 "-benzyloxydecanyl] -4,6-O-isopropylidene-D-glucopyranose 1.7 g of the (S) -2-acyl compound obtained in 8 (c) was treated in the same manner as in Example 8 (d) to give an oil of the title compound 1.
5 g (92%) were obtained.

NMR spectrum (CDCl ₃ ): δ ppm 0.7-1.9 (46H, m); 2.3-2.55 (2H, m); 3.3-4.1 (10H,
m); 4.44 (2H, S); 4.50 (2H, S); 5.1-5.3 (1H, m); 6.6
(1H, d, J = 8.5Hz); 7.32 (10H, s). Infrared absorption spectrum ν _max cm-1 (liquid film); 3310,1740 (W), 1648,1655 (sh). 9 (b) 2-Deoxy-2-[(3'S) -3'-hydroxymyristoylamide] -3-O-[(3 "RS) -3" -hydroxydecanyl] -α-D-glucopyranosyl- 1-
Phosphate The compound (1.17 g, 1.5 mmol) obtained in 9 (a) was treated in the same manner as in Example 8 (e) to obtain 247 mg (25.7%) of the desired product.

NMR spectrum (CD ₃ COOD): 60 MHz δ ppm 0.7-1.0 (6H, m); 1.0-1.6 (34H, m); 2.4-2.8 (2H,
m); 3.4-4.4 (10H, m); 5.64 (1H, m). FAB mass spectrum (M / Z): 640 [MH] ⁻ . Example 10 (a) Allyl 2-deoxy-2-[(2 ′S, 3′R) -2 ′
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 "-(myristoyloxy) myristoyl] -4,6-
O-Isopropylidene-α-D-glucopyranoside 33.1 g of the (2 ′S, 3′R) compound obtained in 2 (a) was
It was dissolved in 0 ml of methylene chloride, 25.9 g of 3-myristoyloxymyristic acid was added, 7 g of 4-dimethylaminopyridine and 12.8 g of N, N'-dicyclohexylcarbodiimide were added, and the mixture was stirred at room temperature for 2 hours. . After filtration, the mixture was concentrated under reduced pressure, and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography and purified with cyclohexane: ethyl acetate = 5: 1 to obtain the target compound in a yield of 47.7 g (85.5%).

NMR spectrum (CDCl ₃ ): δ ppm 0.86-0.90 (9H, m); 1.25-1.77 ｛68H, m, [1.37 (3H,
S); 1.48 (3H, S)]｝; 2.26 (2H, m); 2.49 (1H, d
d, J = 6.3, 15.1 Hz); 2.62 (1H, dd, J = 6.3, 15.1 Hz); 3.70
−3.86 (5H, m); 3.93−3.98 (1H, m); 4.21−4.27 (1H, m
m); 4.63 (1H, d, J = 3.9Hz); 4.90 (1H, dd, J = 2.4,47.4H
z); 5.09-5.21 (7H, m); 5.74-5.84 (1H, m); 6.63 (1
H, dd, J = 3.9,9.8Hz); 7.26-7.36 (5H, m) Infrared absorption spectrum ν _max cm-1 (CHCl ₃ ); 3440,1745,1690,1530. Elemental analysis: Calculated as C62H104NFO12. C: 69.30, H: 9.76, N: 1.30, F: 1.77. Found: C: 69.39, H: 9.86, N: 1.31, F: 1.75. 10 (b) Allyl 2-deoxy-2-[(2 ' S, 3'R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(myristoyloxy) myristoyl] -α-D
-Glucopyranoside 4.6 g of the compound obtained in 10 (a) was treated in the same manner as in 4 (b) to obtain 4.2 g (94.8%) of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm 0.85-0.90 (9H, m); 1.04-1.78 (64H, m); 2.26-2.31
(2H, m); 2.47−2.59 (2H, m; 3,63−3.88 (5H, m); 3.96
−4.02 (1H, m); 4.16−4.23 (1H, m); 4.66 (1H, d, J = 3.
7 Hz); 4.89 (1H, dd, J = 2.2, 47.6 Hz); 5.09−5.21 (7H,
m); 5.73-5.87 (1H, m); 6.66 (1H, dd, J = 3.7,9.5Hz);
7.26-7.37 (5H, m). Infrared absorption spectrum ν _max cm-1 (KBr); 1741, 1719, 1703, 1670, 1545, 1468. Elemental analysis: As C59H100NFO12 Calculated values: C: 68.51, H: 9.74, N: 1.35, F: 1.84. Value: C: 68.62, H: 9.70, N: 1.55, F: 1.80. 10 (c) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(myristoyloxy) myristoyl-6-O-
23.1 g of the compound obtained with benzyloxycarbonyl-α-D-glucopyranoside 10 (d) was treated in the same manner as in 4 (c) to obtain 10.6 g (40.6%) of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm 0.85-0.90 (9H, m); 1.02-1.77 (62H, m); 2.25-2.31
(2H, m); 2.46-2.59 (2H, m); 3.31 (1H, d, J = 4.2Hz);
3.61 (1H, td, J = 9.3,4.2Hz); 3.76-3.86 (2H, m); 3.93
−4.00 (1H, m); 4.16−4.24 (1H, m); 4.38−4.48 (1H, m
m); 4.88 (1H, dd, J = 2.2,47.6Hz); 5.07-5.19 (9H,
m); 5.70-5.85 (1H, m); 6.62 (1H, dd, J = 3.7,9.5Hz);
7.26-7.40 (10H, m). Infrared absorption spectrum ν _max cm-1 (KBr); 1747, 1738, 1724, 1712, 1678, 1547. Elemental analysis: As C67H106NFO14 Calculated values: C: 68, 86, H: 9.14, N: 1.20, F: 1.63 . Obtained value: C: 68.77, H: 9.18, N: 1.42, F: 1.64. 10 (d) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(myristoyloxy) myristoyl] -4-O
-Diphenoxyphosphenyl-6-O-benzyloxycarbonyl-α-D-glucopyranoside 10.47 g of the compound obtained with 10 (c) was treated in the same manner as in 4 (d) to give 11.46 g of the desired compound (91.3%).

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 9H, m); 1.03-1.80 (62H, m); 2.13-2.19
(2H, m); 2.33 (1H, dd, J = 7.3,15.8Hz); 2.42 (1H, dd, J
= 5.1,15.8Hz); 3.75-3.82 (1H, m); 3.89-4.02 (2H,
m); 4.17-4.36 (3H, m); 4.64 (1H, d, J = 3.7Hz); 4.72
(1H, dd, J = 9.2,18.7Hz); 4.85-5.22 (9H, m); 5.42 (1
H, dd, J = 9.2,11.0Hz); 5.70-5.84 (1H, m); 6.56 (1H, d
d, J = 3.7, 9.5 Hz); 7.12-7.65 (20H, m). Infrared absorption spectrum ν _max cm-1 (film); 1750, 1690, 1590. Elemental analysis: C79H115NFO17P, C, H, N, F, P Calculated: 67,74, 8.28, 1.00, 1.36, 2.21. Obtained: 68.77, 9.18, 1.42, 1.64, 2.14. 10 (e) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)- 3 "-(myristoyloxy) myristoyl] -4-O-diphenoxyphosphphenyl-6-O-benzyloxycarbonyl-
The compound (1.4 g) obtained with D-glucopyranose 10 (d) was treated in the same manner as in 1 (g) to obtain 0.77 g (56.6%) of the target compound.

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 9H, m); 1.18-1.82 (65H, m); 2.12-2.18
(2H, m); 2.32 (1H, dd, J = 7.3,15.8Hz); 2.41 (1H, dd, J
= 5.5, 15.8 Hz); 2.70 (1H, dd, J = 1.5, 4.8 Hz); 4.09-4.
18 (3H, m); 4.29-4.34 (1H, m); 4.67 (1H, dd, J = 9.2,1
8.7Hz); 4.87 (1H, m); 4.89 (1H, dd, J = 1.8,47.3Hz);
5.61-5.25 (6H, m); 5.46 (1H, dd, J = 9.2,11.0Hz); 6.6
3 (1H, dd, J = 3.3,8.8Hz); 7.12-7.38 (20H, m). Infrared absorption spectrum ν _max cm-1 (KBr); 1739,1660,1290,1266,1250,1195. Elemental analysis: C, H, N, F, P as C76H111FNO17P Calculated values: 67.09, 8.22, 1.03, 1.40, 2.28. Obtained: 67.04, 7.97, 1.64, 1.35, 2.15. 10 (f) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-hydroxymyristoylamide] -3-O-
6.5 g of the compound obtained with [(3 "R) -3"-(myristoyloxy) myristoyl] -4-O-diphenoxyphosphinyl-D-glucopyranose 10 (e) was treated in the same manner as in 5 (f). And the target compound was obtained in a yield of 4.89 g (93.7%).

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 9H, m); 1.18-1.80 (62H, m); 2.13-2.21
(2H, m); 2.37-2.39 (2H, m); 3.50-3.61 (4H, m); 3.9
7−4.06 (2H, m); 4.21−4.28 (1H, m); 4.65−4.83 (2H, m
m); 5.04-5.13 (1H, m); 5.24-5.28 (2H, m); 5.49-5.
57 (1H, m); 6.80-6.85 (1H, m); 7.14-7.38 (10H, m
m). Infrared absorption spectrum ν _max cm -1 (KBr); 1735,1671,1289,1202,1060. Elemental analysis: C60H99FNO13P, C, H, N, F, P Calculated values: 65.97, 9.13, 1.28, 1.74, 2.84. Found: 65.93, 9.25, 1.48, 1.63, 2.84. 10 (g) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-hydroxymyristoylamide] -3-O-
4.59 g of the compound obtained with [(3 "R) -3"-(myristoyloxy) myristoyl] -D-glucopyranosyl-4-phosphate 10 (f) is treated in the same manner as 5 (g) to give the desired compound Obtained in a yield of 3.9 g (98.7%).

NMR spectrum 270 MHz δ ppm (deuterated pyridine) 0.85 to 0.90 (9H, m), 1.03 to 2.15 (65H, m), 2.43 to 2.4
9 (2H, m), 3.08 ~ 3.25 (2H, m), 4.09 ~ 4.13 (1H, m), 4.
52 ~ 4.56 (2H, m), 4.62 ~ 4.65 (1H, m), 4.99 ~ 5.08 (1
H, m), 5.21-5.49 (2H, m), 5.63-5.74 (2H, m), 6.24-
6.31 (1H, m), 8.03-8.72 (6H, m) Infrared absorption spectrum ν _max cm-1 (KBr); 1734,1661,1550,1465,1224,1182,1171,1063. Elemental analysis: C as C48H91FNO13P , H, N, F, P Calculated: 61.32, 9.76, 1.49, 2.02, 3.29. Obtained values: 60.66, 9.87, 1.68, 1.91, 3.10. Example 11 (a) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristolamide] -3-O-[(3 "R) -3"
-(Myristoyloxy) myristoyl] -4,6-O-
1.1 g of the (2′R, 3 ′s) compound obtained in isopropylidene-α-D-glucopyranoside 2 (a)
0 (a), and treated with 1.36 g (73.8 g) of the target compound.
%).

Infrared absorption spectrum ν _max cm-1 (film); 1740,1685,1530,1460. Elemental analysis: C62H104FNO12 Calculated: C: 69.30, H: 9.76, N: 1.30, F: 1.77. Observed: C: 68 , 94, H: 9.58, N: 1.26, F: 1.76.11 (b) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(myristoyloxy) myristoyl] -α-D
-Glucopyranoside 57.6 g of the compound obtained in 11 (a) was treated in the same manner as in 4 (b) to give the target compound in a yield of 42.6 g (76.8%).

NMR spectrum (CDCl ₃ ): δ ppm 0.86-0.90 (9H, m); 1.25-1.76 (64H, m); 2.25-2.45
(4H, m), 3.64-3.76 (1H, m), 3.85-3.90 (2H, m); 3.9
5-4.00 (1H, m); 4.14-4.21 (2H, m); 4.84-5.32 (H, m
m); 5.83-5.87 (1H, m); 7.07-7.10 (1H, m); 7.26-7.
38 (5H, m). Elemental analysis: C59H100O12NF Calculated: C: 68.51, H: 9.74, N: 1.35, F: 1.84. Found: C: 68.27, H: 9.97, N: 1.48, F: 1.92.11 (c) Allyl 2-deoxy -2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(myristoyloxy) myristoyl] -6-O
-Benzyloxycarbonyl-α-D-glucopyranoside 0.83 g of the compound obtained in 11 (b) was treated in the same manner as in 4 (c) to obtain 0.6 g (63.6%) of the target compound. .

NMR spectrum _{(CDCl 3): δppm 0.86-0.90 (} 9H, m); 1.25-1.76 (63H, m); 2.23-2.45
(4H, m); 3.63-3.65 (2H, m); 3.85-3.98 (2H, m); 4.1
1-4.19 (2H, m); 4.43-4.93 (2H, m); 4.89 (1H, dd, J =
2.6, 47.3Hz); 4.93 (1H, d, J = 3.3Hz); 5.01-5.30 (8H,
m); 5.76-5.92 (1H, m); 7.03-7.07 (1H, m); 7.26-7.
41 (10H, m). Infrared absorption spectrum ν _max cm-1 (film); 1750, 1690. Elemental analysis: Calculated as C67H106O14NF Calculated: C: 68.86, H: 9.14, N: 1.20, F: 1.63. Observed: C: 68.69, H: 9.21, N: 1.40, F: 1.63.11 (d) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)-
3 ″-(myristoyloxy) myristoyl] -4-O
-Diphenoxyphosphinyl-6-O-benzyloxycarbonyl-α-D-glucopyranoside 30.5 g of the compound obtained in 11 (c) is treated in the same manner as in 4 (d), and 31 g of the desired compound is obtained. (96%).

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 9H, m); 1.12-1.72 (65H, m); 2.06-2.12
(2H, m), 2.35 (1H, dd, J = 7.7,17.6Hz); 2.52 (1H, dd, J
= 5.5,17.6Hz); 3.90-4.35 (6H, m); 4.73 (1H, dd, J =
9.2,18.7Hz); 4.89 (1H, dd, J = 2.6,47.6Hz); 4.95 (1H,
d, J = 3.7 Hz); 5.04-5.29 (8H, m); 5.47 (1H, dd, J = 9.
2,11.0Hz); 5.77-5.84 (1H, m); 6.81 (1H, dd, J = 3.3,
8.1Hz); 7.11-7.37 (20H, m). Infrared absorption spectrum ν _max cm-1 (film); 1745, 1690, 1590, 1530. Elemental analysis: C79H115O17NFP, C, H, N, F, P Calculated values: 67,74, 8.28, 1.00, 1.36, 2.21. Obtained: 67.37, 8.25, 0.87, 1.31, 2.27. 11 (e) 2-Deoxy-2-[(2'R, 3'S) -2'-fluoro-3 '-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(3 "R)- 3 "-(myristoyloxy) myristoyl] -4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-
15 g of the compound obtained with D-glucopyranose 11 (d) was treated in the same manner as in 1 (g) to obtain the target compound in a yield of 11.6 g (79.6%).

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 9H, m); 1.14-1.75 (62H, m); 2.08-2.13
(2H, m); 2.33 (1H, dd, J = 7.7,16.9Hz); 2.51 (1H, dd, J
= 4.8,16.9Hz); 3.63 (1H, dd, J = 1.4,4.03Hz); 3.97 (1
H, m); 4.14-4.36 (3H, m); 4.66-4.77 (1H, m); 4.89
(1H, dd, J = 2.7,47.6Hz); 5.02-5.20 (6H, m); 5.30 (1
H, t, J = 3.7Hz); 5.53 (1H, dd, J = 9.2,11,0Hz); 6.92 (1
H, dd, J = 2.9,7.7Hz); 7.12-7.34 (20H, m). Infrared absorption spectrum ν _max cm-1 (CHCl ₃ ); 3420,1750,1690,1590,1530,1490,960. Elemental analysis: C, H, N, F, P as C76N111NO17FP Calculated values: 67,09, 8.22 , 1.03, 1.40, 2.28. Obtained: 67.20, 8.29, 0.95, 1.28, 2.21. 11 (f) 2-Deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-hydroxymyristoylamide] -3-O-
[(3 "R) -3"-(myristoyloxy) myristoyl] -4-O-diphenoxyphosphinyl-D-glucopyranose 11.6 g of the compound obtained in 11 (e) was treated in the same manner as in 5 (f). To give the desired compound in a yield of 8.14 g (87.4%).

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 9H, m); 1.19-1.63 (62H, m); 2.15-2.20
(2H, m); 2.37 (1H, dd, J = 8.4,17.2Hz); 2.68 (1H, d, J
= 8.8Hz): 3.38 (1H, m); 3.59-3.62 (H, m); 4.02-4.0
5 (3H, m); 4.33-4.40 (H, m); 4.74 (1H, dd, J = 1.1,48.
0Hz); 4.77 (1H, dd, J = 9.5,19.1Hz); 5.11-5.15 (1H,
m); 5.30 (1H, t, J = 3.7Hz); 5.54 (1H, dd, J = 9.5,10.3H
z); 6.83 (1H, dd, J = 3.3,9.2Hz); 7.15-7.39 (10H,
m). Infrared absorption spectrum ν _max cm-1 (KBr); 1736,1661,1585,1560,1492.111 (g) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3 '-Hydroxymyristoylamide] -3-O-
7.32 g of the compound obtained with [(3 "R) -3"-(myristoyloxy) myristoyl] -D-glucopyranosyl-4-phosphate 11 (f) were treated in the same manner as 5 (g) to give the desired compound It was obtained quantitatively in a yield of 6.7 g.

NMR spectrum _{(CDCl 3): δppm 0.85-0.91 (} 9H, m); 1.25-2.01 (62H, m); 2.38-2.44
(2H, m); 3.19 (2H, d, J = 5.86Hz); 4.11-4.18 (1H,
m); 4.43-4.59 (3H, m); 4.99-5.07 (1H, m); 5.15-5.
33 ｛(2H, m) [including 5.24 (1H, dd, J = 2.0,48.8Hz)｝
5.74−5.81 (2H, m); 6.28 (1H, t, J = 9.8Hz); 8.02 (1H, m
dd, J = 2.7,9.8 Hz); 8.61 (5H, bs). Infrared absorption spectrum ν _max cm-1 (KBr); 1753,1716,1657,1184,1138,1117,1068. Elemental analysis: C, H, N, F, P as C48H91FNO13P Calculated values: 64, 32, 9.76, 1.49, 2.02, 3.29. Obtained: 61.04, 9.92, 1.60, 1.92, 3.27. Example 12 (a) Allyl 2-deoxy-2-trifluoroacetamido-3-O-[(3'R) -3'-benzyloxytetradecanyl] -4,6-O-isopropylidene-α-D -Glucopyranoside 18.7 g of the compound obtained in 1 (c) and 21 g of 3-benzyloxy-1-mesyloxytetradecane were dissolved in 150 ml of dry dimethylformamide, and 6.9 g of 55% sodium hydride was added in a small amount under ice-cooling. And then added at room temperature for 3 hours.
Stirred for hours. The reaction solution was diluted with ethyl acetate, and neutralized with acetic acid at room temperature. Next, the extract was washed with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The compound obtained here was used for the next reaction without purification.

12 (b) Allyl 2-deoxy-2-amino-3-O-[(3 ′
R) -3'-Benzyloxytetradecanyl] -4,6-
6 g of the compound obtained with O-isopropylidene-α-D-glucopyranoside 12 (a) was treated in the same manner as in 8 (b) to obtain 2.99 g of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm 0.57-0.91 (3H, m); 1.17-1.54 ｛28H, m, [1.39 (3H,
s); 1.47 (3H, s)]｝; 1.75-1.83 (2H, m); 2.71
(1H, m); 3.25 (1H, m); 3.50-3.86 (6H, m); 3.92-4.0
2 (2H, m); 4.14−4.21 (1H, m); 4.47 (1H, d, J = 11.7H
z); 4.55 (1H, d, J = 11.7 Hz); 4.85 (1H, d, J = 3.7 Hz);
5.19-5.34 (2H, m); 5.85-6.00 (1H, m); 7.24-7.35
(5H, m). Elemental analysis: As C33H55NO6 Calculated: C: 70.55, H: 9.87, N: 2.49. Found: C: 70.56, H: 9.87, N: 2.37. Mass spectrum (m / e); 562 (M ⁺⁺ 1); 546; 504; 470; 45
5; 415: 399; 362; 350; 309; 283; 255; 244; 226; 186; 168.12 (c) Allyl 2-deoxy-2-[(3'R) -3'-benzyloxymyristoylamide] -3-O-[(3 ″
R) -3 "-Benzyloxytetradecanyl] -4,6-
2.76 g of the compound obtained with O-isopropylidene-α-D-glucopyranoside 12 (b) was treated in the same manner as in 1 (e) to give the target compound in a yield of 3.37 g (78.1%). .

NMR spectrum _{(CDCl 3): δppm 0.85-0.90 (} 6H, m); 1.25~1.78 (48H, m); 2.31 (1H, d
d, J = 7.3, 15.0 Hz); 2.43 (1H, dd, J = 3.7, 15.0 Hz); 3.36
−3.54 (4H, m); 3.62−3.85 (6H, m); 4.00−4.07 (1H,
m); 4.16-4.24 (1H, m); 4.46 (2H, s); 4.52 (2H, s);
4.78 (1H, d, J = 3.7Hz); 5.11-5.24 (2H, m); 5.68-5.8
6 (1H, m); 6.38 (1H, d, J = 9.2Hz); 7.23-7.38 (10H, m
m). Infrared absorption spectrum ν _max cm-1 (film); 3310, 1642. Elemental analysis: as C54H87NO8 Calculated: C: 73.85, H: 9.98, N: 1.59. Actual: C: 74.04, H: 10.13, N: 1.45. 12 (d) 2-Deoxy-2-[(3'R) -3'-benzyloxymyristoylamide] -3-O-[(3 "R) -3"
-Benzyloxytetradecanyl] -4,6-O-isopropylidene-D-glucopyranose 3.37 g of the compound obtained in 12 (c) was treated in the same manner as in 8 (d) to give 1.68 g of the desired compound ( 52.2%).

NMR spectrum (CDCl ₃ ): δ ppm 0.86-0.91 (6H, m); 1.25-1.77 (48H, m); 2.28 (1H, d
d, J = 7.7,14.7Hz); 2.41 (1H, dd, J = 3.3,14.7Hz); 3.42
−4.04 (11H, m); 5.06 (1H, s); 6.39 (1H, d, J = 8.8H
z); 7.18-7.47 (10H, m). Elemental analysis: As C51H83NO8 Calculated: C: 73.08, H: 9.98, N: 1.67. Found: C: 72, 72, H: 10, 08, N: 1.57. 12 (e) Dibenzyloxyphosphinyl 2 -Deoxy-2-
[(3′R) -3′-benzyloxymyristoylamide] -3-[(3 ″ R) -3 ″ -benzyloxytetradecanyl] -4,6-O-isopropylidene-α-D-glucopyr 1.01 g of the compound obtained in Nocide 12 (d) was dissolved in 15 ml of tetrahydrofuran, and 0.9 ml of n-butyllithium (1.6M hexane solution) was added at -78 ° C under a nitrogen stream. Two minutes later, 5 ml of a solution of 463 mg of dibenzylchlorophosphate in tetrahydrofuran was added. Ten minutes later, the mixture was neutralized with a 0.5 ml solution of acetic acid in 5 ml of tetrahydrofuran. The mixture was diluted with ethyl acetate, washed with water, aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, concentration and purification by silica gel column chromatography gave 964 mg (73%) of the desired product.

NMR spectrum _{(CDCl 3): δppm 0.88 (} 6H, t, J = 6.6-6.9Hz); 1.2-1.8 (42H, m); 1.37
(3H, s); 1.43 (3H, s); 2.24-2.27 (2H, m); 3.23 (1H,
dd, J = 8.4, 10.3 Hz); 3.3-3.5 (2H, m); 3.6-3.75 (6H,
m); 4.1-4.22 (1H, m); 4.35-4.47 (4H, m); 4.99 (2H, m
d, J = 4.8 Hz); 5.03 (2H, d, J = 5.1 Hz); 5.73 (1H, dd, J =
3.4, 5.7Hz); 6.48 (1H, d, J = 8.1Hz); 7.30-7.33 (20H,
m). Infrared absorption spectrum ν _max cm-1 (film); 3310,2930,2860,1660. 12 (f) 2-Deoxy-2-[(3′R) -3′-hydroxymyristoylamide] -3-[( 3 "R) -3" -hydroxytetradecanyl] -4,6-O-isopropylidene-
380 mg of the compound obtained from α-D-glucopyranosyl-1-phosphate 12 (e) was dissolved in 15 ml of tetrahydrofuran, and 1.0 g of 10% palladium carbon was added.
Hydrogenated for hours. After filtration, concentrate to 235mg (92%)
The desired compound was obtained.

NMR spectrum (CDCl ₃ : CD ₃ OD = 1: 1): δ ppm (dissolved by heating): 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 (10H, m); 5.54 (1H, m). Infrared absorption spectrum ν _max cm-1 (CHCl ₃ ); 3300, 2930, 2860, 1650, 1590. FAB-mass spectrum: 736 [MH] ⁻ ; 696; 297; 148. 12 (g) 2-deoxy -2-[(3'R) -3'-hydroxymyristoylamide] -3-[(3 "R) -3" -hydroxytetradecanyl] -α-D-glucopyranosyl-1
-Phosphate 113 mg of the compound obtained in 12 (f) was
After suspending in 0 ml and stirring at room temperature for 1 hour, a white insoluble substance as a target compound was precipitated. 80% at room temperature under reduced pressure
Excluding acetic acid, a powder of the target compound was obtained quantitatively.

NMR spectrum (CDCl ₃ : CD ₃ OD = 1: 1): δ ppm (heat-dissolved, cloudy): 0.89 (6H, t, J = 6.6 Hz); 1.2-1.8
(42H, m); 2.3-2.4 (2H, m); 3.46-3.60 (2H, q, J = 8.7
Hz); 3.65-3.74 (2H, m); 3.77-4.13 (6H, m); 5.57 (1
H, dd, J = 3.2,6.5Hz). Elemental analysis: As C34H68NO11P Calculated: C: 58.52, H: 9.82, N: 2.01, P: 4.44. Observed: C: 57.71, H: 9.69, N: 2.19, P: 4.09. FAB-mass spectrum (M / Z):. 696 [M- H] - example 13 (a) allyl 2-deoxy -2 - [(3'R) -3'- benzyloxy myristoyl amide] -3-O - [(3 "
R) -3 ″ -benzyloxytetradecanyl] -α-O
-Glucopyranoside 1.92 g of the compound obtained in 12 (c) is added to 60 ml of 80% aqueous acetic acid.
And stirred at 60 ° C. for 30 minutes. As it is, it was concentrated under reduced pressure to obtain 1.83 g (99.9
%) Obtained.

NMR spectrum (CDCl ₃ ): δ ppm 0.88 (6H, t, J = 6.6 Hz); 1.2-1.8 (42H, m); 2.02 (1H,
t); 2.35 (1H, dd, J = 7.3,15.0Hz); 2.45 (1H, d, J = 3.8,
15.0Hz); 3.37-3.85 (11H, m); 4.06 (1H, tdd, J = ≦ 1,
5.5,12.8Hz); 4.18 (1H, dt, J = 3.6,9.9Hz); 4.46 (2H,
s); 4.50, 4.55 (2H, ABq, J = 11.0 Hz); 4.76 (1H, d, J = 3.
7Hz); 5.10-5.24 (2H, m); 5.71-5.83 (1H, m); 6.48
(1H, d, J = 9.5 Hz); 7.30-7.33 (10H, m). Infrared absorption spectrum ν _max cm-1 (Nujol); 3325,1640. Elemental analysis: As C51H83NO8 Calculated: C: 73.08, H: 9.98, N: 1.67. Observed: C: 72.65, H: 9.82, N: 1.91. 13 (b) Allyl 2-deoxy-2-[(3'R) -3'-benzyloxymyristoylamide] -3-O-[(3 "
R) -3 "-Benzyloxytetradecanyl] -6-O
-Benzyloxymethyl-α-D-glucopyranoside 900 mg of the compound obtained in 13 (a) was dissolved in 9 ml of methylene chloride, 185 mg of benzylchloromethyl ether and 137 mg of tetramethylurea were added, and the mixture was stirred at room temperature overnight. . The mixture was diluted with ethyl acetate, washed sequentially with aqueous sodium hydrogen carbonate and brine, and dried over magnesium sulfate. After filtration, the mixture was concentrated and purified by a silica gel column. Elution was performed with cyclohexane: ethyl acetate = 2: 1 to obtain 387 mg of the target compound (3
7.7%) as a powder. In addition, 230 mg (25.6%) of the raw material was recovered.

NMR spectrum (CDCl ₃ ): δ ppm 0.88 (6H, t, J = 6.6 Hz); 1.20-1.80 (42H, m); 2.34 (1
H, dd, J = 7.3,15.0Hz); 2.42 (1H, dd, J = 4.0,15.0Hz);
3.18 (1H, bs); 3.38-3.86 (10H, m); 4.06 (1H, dd, J =
5.6, 7.1Hz); 4.25 (1H, dt, J = 3.3, 6.8Hz); 4.46−4.85
(9H, m); 5.09-5.24 (2H, m); 5.73-5.80 (1H, m); 6.4
4 (1H, d, J = 9.5 Hz); 7.2-7.38 (15H, m). Infrared absorption spectrum ν _max cm-1 (Nujol); 3450, 3320, 1640. Elemental analysis: As C59H91NO9 Calculated: C: 73.94, H: 9.57, N: 1.46. Observed: C: 73.72, H: 9.56, N: 1.56. 13 (c) Allyl 2-deoxy-2-[(3'R) -3'-benzyloxymyristoylamide] -3-O-[(3 "
R) -3 "-Benzyloxytetradecanyl] -4-O
-Diphenoxyphosphinyl-6-O-benzyloxymethyl-α-D-glucopyranoside 276 mg of the compound obtained with 13 (b) methylene chloride 3
105 ml of N, N-dimethylaminopyridine and 235 mg of diphenylchlorophosphate were added to the ml solution, and the mixture was stirred overnight.
The mixture was diluted with ethyl acetate, washed sequentially with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, concentration, and purification by silica gel column chromatography, the target compound was obtained quantitatively.

NMR spectrum (CDCl ₃ ): δ ppm 0.88 (6H, t, J = 6.6 Hz); 1.1-1.8 (42H, m); 2.2-2.4
(2H, m); 3.30−4.82 (21H, m); 5.13 (1H, dd, J = 1.5,1
0.30); 5.20 (1H, dd, J = 1.5,17.3Hz); 5.71-5.86 (1
H, m); 6.42 (1H, d, J = 8.2Hz); 7.11-7.65 (25H, m), infrared absorption spectrum ν _max cm-1 (nujol); 3340,1645,1590. Elemental analysis: as C75H100NO11P Calculated: C: 72.60, H: 8.58, N: 1.19, P: 2.64. Observed: C: 72.62, H: 8.40, N: 1.10, P: 2.74. 13 (d) 2-deoxy-2-[( 3'R) -3'-Benzyloxymyristoylamide] -3-O-[(3 "R) -3"
-Benzyloxytetradecanyl] -4-O-diphenoxyphosphinyl-6-benzyloxymethyl-D-glucopyranose 13 mg of the compound obtained in 13 (c) was treated in the same manner as in 8 (d). The target compound was obtained in a yield of 231 mg (66.4%).

NMR spectrum _{(CDCl 3): δppm 0.88 (} 6H, t, J = 7.0Hz); 1.16-1.71 (42H, m); 2.17-2.
36 (2H, m); 2.91-2.92 (1H, d-like); 3.39 (H, m); 3.
59−3.87 (6H, m); 4.08−4.22 (2H, m); 4.35−4.76 (9
H, m); 5.07 (1H, t, J = 3.3Hz); 6.39 (1H, d, J = 8.8Hz);
7.11-7.36 (25H, m). Infrared absorption spectrum ν _max cm-1 (film); 3300,2910,2840,1640,1590. 13 (e) 2-deoxy-2-[(3′R) -3′-benzyloxymyristoylamide] -3 -O-[(3 "R) -3"
-Hydroxytetradecanyl] -4-O-diphenoxyphosphinyl-D-glucopyranose 210 mg of the compound obtained in 13 (d) was prepared in Example 5 (f).
In the same manner as in the above, 105 mg (68%) of the target compound was obtained as a powder.

NMR spectrum (CDCl ₃ ): δ ppm 0.88 (6H, m); 1.2-1.8 (42H, m); 2.1-2.4 (2H, m); 3.
5-4.2 (9H, m); 4.69 (1H, m); 4.92 (1H, bs); 5.45 (1
H, d, J = 3.3Hz); 5.77 (1H, bs); 6.69 (1H, d, J = 8.8H
z); 7.1-7.7 (10H, m). Infrared absorption spectrum ν _max cm-1 (nujol); 3250-3500 (broad), 1655, 1590, 1560. 13 (f) 2-deoxy-2-[(3′R) -3′-hydroxymyristoylamide] -3-O- [3 "R) -3" -hydroxytetradecanyl] -D-glucopyranosyl-4-
100 mg of the compound obtained from the phosphate 13 (e) was added to 10 ml of methanol.
Was dissolved. 15 mg of platinum oxide was added and hydrogenated at room temperature and 1 atm. After 3 to 5 hours, filtration and concentration gave 59 mg (70.5%) of the target compound as a white powder.

NMR spectrum (CDCl ₃ : CD ₃ OD = 1: 1): δ ppm 0.89 (6H, t, J = 6.6 Hz); 1.20-1.83 (42H, m); 2.32 (1
H, dd, J = 8.8,15.4Hz), 2.43 (1H, dd, J = 3.7,15.4Hz);
3.50-4.75 (10H, m); 5.11 (1H, d, J = 3.3Hz). Infrared absorption spectrum ν _max cm-1 (nujol); 3300 (broad), 1650. Example 14 (a) Allyl 2-deoxy-2-[(2 ′S, 3′R) -2 ′
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -4,6-O-isopropylidene-β
-D-glucopyranoside 3.2 g of the (2'S, 3'R) compound obtained in 6 (a)
Treatment was carried out in the same manner as in 2 (b), and 4.12 g (89.2 g) of the target compound was obtained.
%).

14 (b) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -β-D-glucopyranoside Compound obtained with 14 (a) 4 g was treated in the same manner as 4 (b) to give 2.94 g (75.4%) of the desired compound.

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.5-2.0 (71H, m); 2.1-2.8 (4H, m); 3.0-5.9 (18H,
m); 6.3-6.6 (2H, m); 7.1-7.3 (5H, m). 14 (c) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -6-O-benzyloxymethyl-
2.73 g of the compound obtained with β-D-glucopyranoside 14 (b) was treated in the same manner as in 7 (c) to give the desired compound in a yield of 1.7 g (55.5%).

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.7-2.0 (71H, m); 2.1-2.7 (4H, m); 2.90 (1H, bs);
3.4-5.5 (20H, m); 6.2-6.5 (2H, m); 7.1-7.4 (10H, m
m) 14 (d) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -4-O-diphenoxyphosphinyl-6-O-benzyloxymethyl 1.65 g of the compound obtained with -β-D-glucopyranoside 14 (c) was treated in the same manner as in 4 (d) to quantitatively obtain 2.0 g of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.5-2.0 (71H, m); 2.1-2.7 (4H, m); 3.5-5.6 (20H,
m); 6.2-6.7 (2H, m); 7.1-7.5 (20H, m). 14 (e) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -Benzyloxymyristoyl] -4-O-diphenoxyphosphinyl-6
1.9 g of the compound obtained with -O-benzyloxymethyl-D-β-glucopyranose 14 (d) was treated in the same manner as in 1 (g) to obtain 0.88 g (47.5%) of the target compound. .

NMR spectrum _{(CDCl 3): δppm 0.88 (} 9H, t, J = 6.2-7.0Hz); 1.15-1.70 (62H, m); 2.2
0-2.45 (H, m); 3.07 (1H, m); 3.60-3.82 (3H, m); 4.2
0−4.90 (10H, m); 5.17 (1H, m); 5.30 (1H, t, J = 3.3−
3.77); 5.57 (1H, dd, J = 9.4,10.8Hz); 6.68 (1H, dd, J
= 3.5, 8.6 Hz); 7.1-7.35 (20H, m). Infrared absorption spectrum ν _max cm-1 (film); 3450-3300, 2920, 2860, 1740, 1680. 14 (f) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro -3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -hydroxymyristoyl] -4-O-diphenoxyphosphinyl-D-glucopyranose 14 (e). 0.78 g of the obtained compound was treated in the same manner as in 7 (f) to give the desired compound in a yield of 0.37 g (51.4%).

NMR spectrum (CDCl ₃ ): δ ppm 0.88 (9H, t, J = 6.2-7.0 Hz); 1.10-1.30 (58H, m); 1.4
0-1.75 (4H, m); 2.10-2.33 (4H, m); 3.50-4.10 (7H,
m); 4.70-4.98 (3H, m); 5.13-5.40 (2H, m); 5.56 (1
H, t, J = 9.5-10.3Hz); 6.77 (1H, dd, J = 3.7,9.2Hz); 7.
15-7.38 (10H, m). 14 (g) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -Hydroxymyristoyl] -D-glucopyranosyl-4-phosphate 0.29 g of the compound obtained with 14 (f) was treated in the same manner as 5 (g) to give 0.25 g of the desired compound quantitatively.

NMR Spectrum _{(CF 3 COOD): δppm 0.87-0.98} (9H, m); 1.20-1.55 (5H, m); 1.55-2.00
(4H, m); 2.43-2.64 (2H, m); 2.73-2.94 (2H, m); 4.1
4-4.65 (5H, m); 4.79 (1H, dd, J = 9.3,18.5Hz); 5.15
(1H, dd, J = 1.0,46.9Hz); 5.40-5.78 (3H, m). FAB-mass spectrum, NEG, (M / Z): 938 [MH] ^- . Example 15 (a) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -4,6-O-isopropylidene-β
3.4 g of the (2′R, 3 ′S) compound obtained in -D-glucopyranoside 6 (a)
Treated in the same manner as in 2 (b), 3.8 g (77.4%) of the target compound
In the yield.

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.5-2.0 (77H, m); 2.0-2.8 (4H, m); 3.2-5.6 (16H,
m); 6.1-6.4 (2H, m); 7.1-7.4 (5H, m). 15 (b) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -β-D-glucopyranoside Compound obtained with 15 (a) 3.68 g was treated in the same manner as 4 (b) to give 2.97 g (84%) of the desired compound.

15 (c) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -6-O-benzyloxymethyl-
2.77 g of the compound obtained with β-D-glucopyranoside 15 (b) was treated in the same manner as in 7 (c) to give 2.36 g (76%) of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.6-2.0 (71H, m); 2.0-2.7 (4H, m); 3.4-6.2 (21H,
m, OH); 6.2-6.6 (2H, m); 7.1-7.5 (10H, m). 15 (d) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -benzyloxymyristoyl] -4-O-diphenoxyphosphinyl-6-O-benzyloxymethyl 2.25 g of the compound obtained with -β-D-glucopyranoside 15 (c) was treated in the same manner as in 4 (d) to obtain 2.36 g (86.4%) of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.6-2.0 (71H, m); 2.1-2.4 (4H, m); 3.5-6.1 (20H,
m); 6.1-6.6 (2H, m); 7.1-7.5 (20H, m). 15 (e) 2-Deoxy-2-[(2'R, 3'S) -2'-fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -Benzyloxymyristoyl] -4-O-diphenoxyphosphinyl-6
2.2 g of the compound obtained with -O-benzyloxymethyl-D-glucopyranose 15 (d) was treated in the same manner as for 1 (g) to obtain 1.83 g (85.7%) of the target compound.

NMR spectrum (CDCl ₃ ): δ ppm, 60 MHz 0.5-2.0 (71H, m); 2.1-2.6 (4H, m); 3.6-5.9 (17H,
m); 6.75 (1H, bs); 7.1-7.4 (20H, m). 15 (f) 2-Deoxy-2-[(2'R, 3'S) -2'-fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -Hydroxymyristoyl] -4-O-diphenoxyphosphinyl-β-D
-1.7 g of the compound obtained with glucopyranose 15 (e) was treated in the same manner as in 7 (f) to give 0.6 g (42.1%) of the target compound.

15 (g) 2-Deoxy-2-[(2'R, 3'S) -2'-fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-[(3 "R) -3" -Hydroxymyristoyl] -D-glucopyranosyl-4-phosphate 0.54 g of the compound obtained with 15 (f) was treated in the same manner as 5 (g) to give the desired compound in a yield of 0.45 g (96.8%).

NMR Spectrum _{(CF 3 COOD): δppm 0.87-0.98} (9H, m); 1.27-1.60 (58H, m); 1.65-1.93
(4H, m); 2.50-2.60 (2H, m); 2.80-2.90 (2H, m); 4.1
2-4.62 (5H, m); 4.80 (1H, dd, J = 9.5,18.3Hz); 5.18
(1H, dd, J = 2.7,48.6Hz); 5.40-5.93 (3H, m). FAB-mass spectrum, NEG, (M / Z): 938 [MH] ^- . Example 16 (a) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -4,6-O-isopropylidene-β-D-glucopyranoside and allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -4,6-O-isopropylidene-β-D-glucopyranoside 5.18 g (20 mmol) of the compound obtained in Example 1 (d) was dissolved in 150 ml of methylene chloride. And 9.93 g of (±) -syn-2-fluoro-3-myristoyloxymyristate was added,
Further, 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,
Diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and 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: ethyl acetate = 3: 1.
(2′R, 3 ′S) form, which is the target compound,
5.65 g (39.6%) and 5.55 g of the (2'S, 3'R) form
(38.9%).

[(2′R, 3 ′S) form] NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (6H, t, J = 6.9 Hz), 1.20-1.38 (38H, m), 1.44 (3
H, s), 1.52 (3H, s), 1.60-1.84 (5H, m) 2.30 (2H,
t), 3.23-3.33 (1H, m), 3.58-3.85 (4H, m), 3.93 (1
H, dd, J = 5.5,10.6Hz), 4.07 (1H, dd, J = 6.2,12.8Hz),
4.30−4.37 (1H, m), 4.76 (1H, d, J = 7.7Hz), 4.93 (1H, m
dd, J = 2.9,48.0Hz), 5.20-5.36 (3H, m), 5.79-5.94
(1H, m), 6.44 (1H, t, J = 5.5Hz). [(2'S, 3'R) form] 0.88 (6H, t, J = 6.9Hz), 1.20-1.38 (38H, m), 1.45 (3
H, s), 1.52 (3H, s), 1.56-1.76 (5H, m), 2.29 (2H,
t), 3.30-3.41 (2H, m), 3.57 (1H, t, J = 9.2Hz), 3.80
(1H, t, J = 10.6Hz), 3.93 (1H, dd, J = 5.5,11.0Hz), 4.0
5−4.16 (2H, m), 4.29−4.36 (1H, m), 4.77 (1H, d, J =
8.1Hz), 4.89 (1H, dd, J = 2.2,48.0Hz), 5.20-5.34 (3
H, m), 5.80-5.89 (1H, m), 6.52 (1H, t, J = 5.5Hz). 16 (b) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3 '-(myristoyloxy) myristoylamide] -3-O-myristoyl-4,6-O-isopropylidene-β-D-glucopyranoside Compound (2′R , 3'S) 2g (2.8
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 stirred at room temperature for 1 hour. It was concentrated, diluted with ethyl acetate, washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column and purified with cyclohexane: ethyl acetate = 5: 1 to obtain the desired compound in 1.3.
Obtained in a yield of 5 g (52.1%).

Infrared absorption spectrum νmax (CHCl ₃ ): 1740,1695 cm−1. Mass spectrum M / Z: 924 (M ⁺⁺ 1), 909,883,867,737,
724,655,638,610,526,513,452. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.6 Hz), 1.13-1.67 ｛70H, m [1.36 (3H,
s), 1.46 (3H, s)]｝, 2.25-2.35 (4H, m), 3.32
−3.41 (1H, m), 3.66−3.85 (3H, m), 3.95 (1H, dd, J =
5.5,10.6Hz), 4.05 (1H, dd, J = 6.2,12.8Hz), 4.26-4.3
4 (1H, m), 4.74-4.93 (H, m), 5.16-5.29 (4H, m), 5.7
5-5.89 (1H, m), 6.34 (1H, dd, J = 4.4,8.8Hz). Elemental analysis: as C ₅₄ H ₉₈ FNO ₉ 16 (c) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-β-D-glucopyranoside The compound obtained with 16 (b) was treated in the same manner as in Example 4 (b) to give the desired compound. Obtained in 2 g (80.4%) yield of compound.

NMR spectrum (60 MHz, CDCl ₃ ) δ ppm 0.66-1.91 (74H, m), 2.09-2.55 (H, m), 2.87-6.16
(15H, m), 6.54 (1H, m). 16 (d) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-6-D-benzyloxycarbonyl-β-D-glucopyranoside 1.9 g (2.15 mmol) of the compound obtained from 16 (c) was obtained. After dissolving in 20 ml of methylene chloride, 550 mg of benzyloxychloroformate was added, and 327 mg of triethylamine was further added, followed by stirring at room temperature for 5 hours. It was concentrated and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the 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 mg (30.2%).

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.9 Hz), 1.25-1.65 (66H, m), 2.25-2.
36 (4H, m), 2.82 (1H, s), 3.59-3.66 (2H, m), 4.03 (1
H, dd, J = 6.2,12.8Hz), 4.27 (1H, dd, J = 5.1,12.8Hz),
4.42-4.52 (1H, m), 4.81 (1H, dd, J = 3.7,47.6Hz), 4.8
4 (1H, d, J = 8.1 Hz), 5.14-5.27 (6H, m), 5.76-5.89
(1H, m), 6.37 (1H, dd, J = 4.4,8.1Hz), 7.34-7.40 (5
H, m). 16 (e) Allyl 2-deoxy-2-[(2'R, 3'S) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-β
-D-Glucopyranoside 600 mg (0.589 mmol) of the compound obtained in 16 (d) is dissolved in 20 ml of methylene chloride, and diphenylchlorophosphate is dissolved.
474.8 mg was added, and 62.6 mg of triethylamine was further added, followed by stirring at room temperature overnight. It concentrated under reduced pressure and diluted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After filtration, the ethyl acetate was distilled off under reduced pressure. The residue was applied to a silica gel column, and cyclohexane: ethyl acetate = 5:
Purification was performed in 1 to give the desired compound in a yield of 600 mg (81.4%).

Infrared absorption spectrum νmax (CHCl ₃ ): 1743,1690 cm -1 NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9H, t, J = 6.9 Hz), 1.05-1.73 (64H, m), 2.11-2.
3. (4H, m), 3.46-3.56 (1H, m), 3.77-3.82 (1H, m), 4.
03 (1H, dd, J = 6.2,12.8Hz), 4.19-4.38 (3H, m), 4.63
−4.89 (2H, m), 5.01−5.26 (6H, m), 5.64−5.87 (2H, m
m), 6.37 (1H, dd, J = 4.4,7.7Hz), 7.11-7.34 (15H,
m). Elemental analysis: as C ₇₁ H ₁₀₉ FNO ₁₄ P 16 (f) 2-Deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxycarbonyl-D-glucopyranose The compound obtained in 16 (e) was treated in the same manner as in Example 1 (g), The target compound was obtained in a yield of 490 mg (84.3%).

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9H, t, J = 7.0 Hz), 1.11-1.66 (6H, m), 2.11-2.2
9 (4H, m), 3.36 (1H, s), 4.13-4.39 (4H, m), 4.71-5.
56 (7H, m), 6.70 (1H, dd, J = 3.3,8.1Hz), 7.11-7.35
(15H, m). 16 (g) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-myristoyloxymyristoylamide]-
490 mg of the compound obtained with 3-O-myristoyl-4-O-diphenoxyphosphinyl-D-glucopyranose 16 (f) was dissolved in 30 ml of tetrahydrofuran, 1 g of 10% palladium carbon was added, and the mixture was added at room temperature. Catalytic reduction was carried out for 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 desired compound in a yield of 270 mg (75.9%).

Infrared absorption spectrum νmax (CHCl ₃ ): 1735,1685cm-1 Elemental analysis: As C ₆₀ H ₉₉ FNO ₁₂ P 16 (h) 2-deoxy-2-[(2'R, 3'S) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-D-glucopyranosyl-4-phosphate The compound obtained with 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: 922 (MH) ^- . Example 17 (a) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3 '-(myristoyloxymyristoylamide) -3-O-myristoyl-4,6-O-isopropylidene-β-D-glucopyranoside Compound (2 ′S, 3'R) body 2.9g
(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 further added. The mixture was stirred at room temperature for 1 hour, but the reaction did not proceed. Further, 50 mg of 4-dimethylaminopyridine was added, and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure, diluted with ethyl acetate, and the ethyl acetate layer was washed with aqueous sodium hydrogen carbonate 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 quantitatively obtain the target compound.

NMR spectrum (60 MHz, CDCl ₃ ) δ ppm 0.66-2.01 (79H, m), 2.05-2.61 (4H, m), 3.30-6.23
(14H, m), 6.85 (1H, m). 17 (b) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-β-D-glucopyranoside The compound obtained in 17 (a) was treated in the same manner as in Example 4 (b) to give the desired compound Obtained in a yield of 3.08 g (84.7%).

17 (c) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-6-O-benzyloxymethyl-β-D-glucopyranoside 2.7 g (3.05 mmol) of the compound obtained in 17 (b) was obtained. , Dissolved in 50 ml of methylene chloride and benzyl chloromethyl ether
0.525 g was added, and 0.355 g of tetramethyl urea was further added.
Time refluxed. The 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 2.08 g (67.8%) of the target compound.

Infrared absorption spectrum νmax (CHCl ₃ ): 3430,1738,1695cm-1 Mass spectrum M / Z: 986,928,834,775,717,596,509,45
6,383,354,298,285,268. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9 H, t, J = 6.9 Hz), 1.20-1.73 (65 H, m), 2.24-2.
37 (4H, m), 3.47−3.51 (1H, m), 3.74 (1H, t, J = 9.5H
z), 3.89-4.11 (4H, m), 4.26-4.33 (1H, m), 4.59 (1
H, d, J = 8.4Hz), 4.63 (2H, s), 4.79 (1H, dd, J = 4.3,48.
4Hz), 4.81 (2H, s), 5.03 (1H, dd, J = 9.2,10.6Hz), 5.1
5-5.30 (3H, m), 5.80-5.88 (1H, m), 6.36 (1H, dd, J =
4.4, 9.2Hz), 7.29-7.36 (5H, m). 17 (d) Allyl 2-deoxy-2-[(2'S, 3'R) -2 '
-Fluoro-3'-myristoyloxymyristoylamide] -3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxymethyl-β-D
-The compound obtained in glucopyranoside 17 (c) was treated in the same manner as in Example 16 (e) to quantitatively obtain the target compound.

Infrared absorption spectrum νmax (CHCl ₃ ): 3430,1740,1695cm-1 Mass spectrum M / Z: 1014,994,758,670,580,440,322,2
68. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9 H, t, J = 6.9 Hz), 1.10-1.68 (65 H, m), 2.08-2.
31 (3H, m), 3.65-3.69 (2H, m), 3.78-3.84 (1H, m),
4.03-4.11 (2H, m), 4.25-4.32 (1H, m), 4.50-4.85
(7H, m), 5.15-5.39 (4H, m), 5.76-5.83 (1H, m), 6.3
8 (1H, dd, J = 4.8,9.2Hz), 7.13-7.44 (15H, m). 17 (e) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-4-O-diphenoxyphosphinyl-6-O-benzyloxymethyl-D-glucopyranose The compound obtained in 17 (d) was treated in the same manner as in Example 1 (g). The compound was obtained in a yield of 1.58 g (71%).

NMR spectrum (60 MHz, CDCl ₃ ) δ ppm 0.63-2.42 (77 H, m), 3.55-5.78 ｛14 H, m [4.54 (2H,
s), 4.66 (2H, s)]｝, 6.70 (1H, m), 7.00-7.53
(15H, m). 17 (f) 2-Deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-4-O-diphenoxyphosphinyl-D-glucopyranose 1.44 g (1.2 mmol) of the compound obtained in 17 (e) was dissolved in 30 ml of methanol, and 1 g of 10% palladium carbon was added. 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.
Purification was performed with cyclohexane: ethyl acetate = 1: 1 to obtain the desired compound in a yield of 715 mg (55.2%).

Infrared absorption spectrum νmax (CHCl ₃ ): 3440,1740,1690cm-1 Elemental analysis: As C ₆₀ H ₉₉ FNO ₁₂ P Example 17 (g) 2-deoxy-2-[(2'S, 3'R) -2'-fluoro-3'-myristoyloxymyristoylamide]-
3-O-myristoyl-D-glucopyranosyl-4-phosphate The compound obtained with 17 (f) was treated in the same manner as in Example 5 (g) to give the desired compound in a yield of 420 mg (89%).

Mass spectrum NEG, FAB / MS, M / Z: 922 (MH) ^- . Example 18 (a) (R, S) -3-benzyloxycarbonyloxy-2,2
-Dissolve 2.2 g of difluoromyristic acid in 20 ml of dry dichloromethane, add 2 ml of oxalic acid chloride and add N, N
-One drop of dimethylformamide was added and the mixture was stirred at room temperature for 1 hour. Dichloromethane was distilled off under reduced pressure to obtain an acid chloride. Allyl 2-deoxy-2 obtained in Example 1 (d)
1.51 g of -amino-4,6-O-isopropylidene-β-D-glucopyranoside was dissolved in 20 ml of dry dichloromethane, 700 mg of triethylamine was added, and acid chloride was added under ice cooling. After stirring at room temperature for 1 hour, dichloromethane was distilled off under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and saturated saline, 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 (2: 1) to obtain 2.64 g (75.8%) of the target compound.

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (3H, t, J = 6.2-7.0 Hz)), 1.25-1.61 ｛24H, m [1.
45 (3H, s), 1.52 (3H, s)]｝, 1.72-1.79 (2H,
m), 2.95 (0.5H, d, J = 3.3Hz), 3.11 (0.5H, d, J = 3.3H)
z), 3.21-3.60 (3H, m), 3.76-4.13 (4H, m), 4.23-4.
33 (1H, m), 4.70 (0.5H, d, J = 8.4Hz), 4.81 (0.5H, d, J
= 8.4Hz), 5.14−5.31 (5H, m), 5.75−5.91 (1H, m), 6.
47−6.54 (1H, m), 7.30−7.40 (5H, m). Infrared absorption spectrum νmax (CHCl ₃ ): 3430,2925,2850,1755,1705,1535,1380,1263cm-1 Mass spectrum M / Z: 655 (M ⁺ ), 640,597,532,468,385,
360,242,227,184,143,108,101,91,69,43. Elemental analysis: as C ₃₄ H ₅₁ F ₂ NO _9. 18 (b) Allyl 2-deoxy-2-[(RS) -2 ', 2'-difluoro-3'-(benzyloxycarbonyloxy) myristoylamide] -4,6-O-isopropylidene-3
-O-[(R) -3 ″ -myristoyloxymyristoyl] -β-D-glucopyranoside (R) -3-myristoyloxymyristate 230 mg
(0.5 mmol) was treated with 0.5 ml of oxalyl chloride in 4 ml of dichloromethane for 2 hours and acid chloride was added.
Excess oxalyl chloride and solvent are removed and dried. 262 mg (0.4 mmol) of the compound obtained in Example 18 (e) and 50 mg of triethylamine are dissolved in 5 ml of dichloromethane, sufficiently cooled on ice, and then the solution of the above acid chloride in 5 m of dichloromethane is dissolved.
l was added dropwise. In about 3 hours, the raw materials are gone,
After removing the solvent, the mixture was diluted with ethyl acetate, and post-treated with a 5% aqueous sodium hydrogencarbonate solution and a saturated saline solution, and then purified by column chromatography (silica gel 20 g, developing solvent: cyclohexane: ethyl acetate = 5: 1). The yield is 325.8
mg (74.3%).

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.85-0.90 (9H, m), 1.20-1.80 (68H, m), 2.20-2.31
(2H, m), 2.43-2.66 (2H, m), 3.35 (1H, m), 3.68-4.0
7 (6H, m), 4.26 (2H, m), 4.58 (1H, m), 5.11-5.41 (7
H, m), 5.74 (1H, m), 6.58 (1H, m), 7.29-7.38 (5H,
m). Infrared absorption spectrum νmax (liquid film): 3350, 2925, 2850, 1780, 1710 cm-118 (c) Allyl 2-deoxy-2-[(RS) -2 ', 2'-difluoro-3'-(benzyl (Oxycarbonyloxy) myristoylamide] -3-O-[(R) -3 ″ -myristoyloxymyristoyl] -β-D-glucopyranoside To 0.2 g of the compound obtained from 18 (b), 50 ml of 85% acetic acid was added ,
Stir at 60 ° C. for 50 minutes. The acetic acid was removed under reduced pressure, dried with a vacuum pump, and purified by 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 complete the reaction quickly by using as much acetic acid as possible. If the amount of acetic acid is small, a by-product is formed and the yield is reduced.

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.85-0.90 (9H, t, J = 6.4-6.8 Hz), 1.18-1.42 (47H,
m), 1.43-1.80 (15H, m), 1.90-2.00 (1H, m), 2.09 (1
H, t, J = 5.9-6.4Hz), 2.25-2.32 (2H, m), 2.41-2.50
(2H, m), 3.37-3.53 (1H, m), 3.63-3.70 (2H, m), 3.7
8−4.08 (5H, m), 4.21−4.34 (1H, m), 4.53 (0.4H, d, J
= 8.3Hz), 4.59 (0.6H, d, J = 8.3Hz), 4.92-5.36 (7H,
m), 5.74-5.88 (1H, m), 6.59 (0.6H, d, J = 8.8Hz), 6.6
9 (0.4H, d, J = 8.8Hz), 7.35-7.39 (5H, m). Infrared absorption spectrum νmax (Nujol): 3350, 3450, 3300, 2950, 1760, 1690, 1620, 1550 cm-1 Elemental analysis: C ₆₁ H ₁₀₀ F ₂ NO ₁₂ Analysis value: C 67.24, H 9.04, N 1.68, F 3.41 (%) Theoretical: C 68.00, H 9.28, N 1.30, F 3.53 (%) 18 (d) Allyl 6-O-benzyloxycarbonyl-2-deoxy-2-[(RS) -2 ', 2 '-Difluoro-3'-
(Benzyloxycarbonyloxy) myristoylamide] -3-O-[(R) -3 ″ -myristoyloxymyristoyl] -β-D-glucopyranoside 120 mg (0.11 mmol) of the compound obtained from 18 (c) and benzyl Dissolve 25.4 mg (1.3 equivalents) of oxycarbonyl chloride in 20 ml of dichloromethane, add ice-cooled 17.2 mg (1.5 equivalents) of dimethylaminopyridine, stir for 30 minutes, return to room temperature, and stir for 2 hours. The product was purified by chromatography [silica gel 100 g, developing solvent (cyclohexane: ethyl acetate = 2: 1)] to give the desired product in a yield of 80 mg (59.2
%), The protected substance in both the 4th and 6th positions was obtained in a yield of 36mg.
(26.7%).

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.88 (9 H, t, J = 6.35-6.83 Hz), 1.25-1.73 (62 H, m),
2.24−2.31 (2H, m), 2.41−2.48 (2H, m), 3.52−3.69
(4H, m), 3.90−4.02 (3H, m), 4.18−4.30 (1H, m), 4.42−4.57 (3H, m), 5.02−5.25
(7H, m), 5.68-5.85 (1H, m), 6.48-6.52 (1H, d), 6.5
8-6.65 (1H, d), 7.32-7.40 (10H, m). Infrared absorption spectrum νmax (Nujol): 3500, 3300, 2900, 2850, 1720, 1690, 1540 cm-1 Elemental analysis: C ₆₉ H ₁₀₆ F ₂ NO ₁₄ Analysis value: C 67.19, H 8.75, N 0.89, F 2.99 (%) Theoretical: C 68.41, H 8.75, N 1.16, F 3.14 (%) 18 (e) Allyl 6-O-benzyloxycarbonyl-2-
[(RS) -2 ', 2'-difluoro-3'-(benzyloxycarbonyloxy) myristoylamide] -4-O
-Diphenoxyphosphinyl-2-deoxy-3-O-
[(R) -3-myristoyloxymyristoyl] -β
0.5 g of the compound obtained by -D-glucopyranoside 18 (d), diphenylphosphoryl chloride and dimethylaminopyridine were added in excess of 1 g each, and the mixture was heated under reflux for 3 hours using 50 ml of tetrahydrofuran as a solvent. After removing the solvent under reduced pressure, the residue was diluted with ethyl acetate, and post-treated with a 5% aqueous sodium hydrogen carbonate solution and a saturated saline solution. Column chromatography [silica gel 30 g, developing solvent (cyclohexane: ethyl acetate = 3:
1)] to give a yield of 0.62 g (97.5%).

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.90 (9H, t, J = 6.8 Hz), 1.14-1.75 (62H, m), 2.12-2.
41 (3H, m), 3.61−3.83 (3H, m), 3.91−4.04 (1H, m),
4.13-4.23 (2H, m), 4.30-4.38 (1H, m), 4.69 (1H, dd
d, J = 9.0,9.0,18.0Hz), 4.85 (1H, d, J = 7.0Hz), 4.99−
5.39 (7H, m), 5.47-5.63 (2H, m), 5.67-5.85 (1H,
m), 6.80 (1H, d, J = 7.0Hz), 6.95 (1H, d, J = 7.0Hz), 7.
10−7.36 (20H, m). Infrared absorption spectrum .nu.max (liquid film): 3300,2900,2850,1750,1700,1590,1540cm-1 Elementary analysis: as _{C 81 H 115 F 2 NO 17} P 18 (f) 6-O-benzyloxycarbonyl-4-O-diphenoxyphosphinyl-2-deoxy-2-[(RS)-
2 ', 2'-difluoro-3'-(benzyloxycarbonyloxy) myristoylamide] -3-O-[(R)
-3-myristoyloxyristoyl] -D-glucopyranoside 30 mg of 1,5-cyclooctadiene bis [methyldiphenylphosphine] iridium hexafluorophosphate (5% mol) was added to 50 mg of the compound obtained by 18 (e). ),
Dissolve in 5 ml of tetrahydrofuran, replace with nitrogen, and then replace 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. Add 1 ml of concentrated hydrochloric acid, and
For 2 hours, and purified by preparative thin-layer chromatography (1 mm) to obtain 40 mg (82.1%) of the desired product.

NMR spectrum (270 MHz, CDCl ₃ ) δ ppm (R, S mixed) 0.83-0.90 (9H, t, J = 6.5-6.8 Hz), 1.16-1.74 (62H,
m), 2.09-2.18 (2H, m), 2.32-2.49 (2H, m), 2.73-2.
74 (0.5H, m), 3.28-3.29 (0.5H, m), 4.01-4.38 (4H,
m), 4.63-4.74 (1H, m), 4.89-5.23 (8H, m), 5.33-5.
47 (1H, m), 6.72-6.73 (1H, m), 7.12-7.37 (20H,
m). Infrared absorption spectrum .nu.max (liquid film): 3350,2925,2850,1750,1710,1590,1540,1490,1460cm-1 Elementary analysis: as _{C 78 H 111 F 2 NO 17} P 18 (g) 4-O-diphenoxyphosphinyl-2-deoxy-2
-[(RS) -2 ', 2'-difluoro-3'-hydroxymyristoylamide] -3-O-[(R) -3-myristoyloxymyristoyl] -D-glucopyranoside In 2 ml of tetrahydrofuran, 18 ( 30 mg of the compound obtained in f) and 20 mg of 10% palladium on carbon were added, the mixture was replaced with hydrogen using an aspirator, stirred at room temperature for 6 hours, and left overnight.

Developed by preparative thin-layer chromatography [1 mm, developing solvent (cyclohexane: ethyl acetate = 1: 1)], 10 mg (4 mg) of each of the two target compounds each having a 2-position substituent of R or S
1.2%).

[2R form (lower Rf)] NMR spectrum (270 MHz, CDCl ₃ ) δ ppm 0.85-0.90 (9H, t, J = 6.34-6.36 Hz), 1.20-1.68 (62
H, m), 2.17-2.23 (2H, m), 2.34-2.47 (2H, m), 3.10
(1H, d, J = 4.5Hz), 3.18-3.27 (2H, m), 3.54-3.61 (1
H, m), 3.92-4.03 (3H, m), 4.27-4.36 (1H, m), 4.78
(1H, q, J = 9.2Hz), 5.02-5.11 (1H, m), 5.36 (1H, t, J
= 3.42Hz), 5.53 (1H, t, J = 9.28Hz), 6.87-6.91 (1H,
m), 7.14-7.39 (10H, m). Infrared absorption spectrum .nu.max (Nujol): 3500,3450,3375,2900,2850,1730,1680,1600cm-1 [2S body (Rf those above)] NMR spectrum _{(270MHz, CDCl 3) δppm 0.85-0.90} ( 9H, t, J = 6.3-6.41Hz), 1.21-1.68 (62H,
m), 2.17−2.23 (3H, m), 2.34−2.50 (2H, m), 3.08 (1
H, d, J = 4.4Hz), 3.18-3.29 (2H, m), 3.54-3.61 (1H,
m), 3.94-4.00 (3H, m), 4.27-4.36 (1H, m), 4.79 (1
H, q, J = 9.4Hz), 5.02-5.12 (1H, m), 5.36 (1H, t, J = 3.
42Hz), 5.53 (1H, t, J = 9.73Hz), 6.92-7.01 (H, m), 7.
14-7.39 (10H, m). Infrared absorption spectrum νmax (nujol): 3500, 3450, 3375, 2900, 2850, 1730, 1680, 1600 cm-118 (h) 2-deoxy-2-[(R or S) -2 ', 2'-difluoro -3'-hydroxymyristoylamide] -3-O
-[(R) -3-myristoyloxymyristoyl]-
To 2 ml of D-glucopyranosyl-4-phosphate tetrahydrofuran, 60 mg of each compound obtained in 18 (g) and 5 mg of platinum oxide were added, and the mixture was replaced with hydrogen using an aspirator and stirred at room temperature for 3 hours. Platinum oxide is removed by filtration, and tetrahydrofuran is removed under reduced pressure. Of the two target compounds in which the 2-substituent is R or S, those having a higher Rf value from the starting compound having a higher Rf value
50 mg (95%) and 52 mg (97%) of the lower Rf value were obtained from the starting compound having the lower Rf value [developing solvent (chloroform: ethanol: ethyl acetate: water = 8: 5: 2: 1)]. .

[2R form (Rf is lower)] NMR spectrum (270 MHz, d ₅ -pyridine + heavy water) δ ppm: 0.
85−0.90 (9H, m), 1.14−2.04 (62H, m), 2.39−2.48 (2
H, m), 3.05-3.14 (1H, m), 3.28-3.37 (1H, m), 4.07-
4.11 (1H, m), 4.49−4.66 (3H, m), 4.88−4.98 (1H,
m), 5.18-5.29 (1H, m), 5.71-5.81 (2H, m), 6.17-6.
32 (1H, m). Infrared absorption spectrum νmax (Nujol): 3500,3350,2900,2850,1720,1680,1590,1540,1490,1460c
m-1 [2S body (Rf those above)] NMR spectrum (270MHz, d ₅ - pyridine + heavy water) δppm: 0.
88−0.97 (9H, m), 1.24−2.02 (62H, m), 2.33−2.48 (2
H, m) 2.92−3.01 (2H, m), 3.36−3.59 (1H, m), 4.11−
4.22 (1H, m), 4.53-4.69 (3H, m), 4.93-5.04 (1H,
m), 5.49-5.56 (1H, m), 5.68-5.74 (1H, m), 5.82-5.
83 (1H, m), 6.26-6.38 (1H, m). Infrared absorption spectrum νmax (Nujol): 3500,3350,2900,2850,1720,1680,1590,1540,1490,1460c
m-1 Example 19 Triethylamine Salt of Phosphoric Acid Compound 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 (g), 16 (h),
When it is necessary to obtain the water-soluble triethylamine salt of the phosphoric acid compound obtained in 17 (g) and 18 (h), Example 8
The same operation as (f) is performed.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/70 AED A61K 31/70 AED (72) Inventor Tetsuo Hiraoka 1-258 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Minoru Akamatsu 1-26-21 Shimizu, Suginami-ku, Tokyo (72) Inventor Masahiro Nishijima 1-4-29-A-101, Miyamae-ku, Miyamae-ku, Kawasaki, Kanagawa Prefecture (56) References JP-A-63 JP-A-44588 (JP, A) JP-A-62-129292 (JP, A) JP-A-62-108895 (JP, A) JP-A-54-122226 (JP, A) JP-A-60-501259 (JP, A) (58) Fields surveyed (Int. Cl. ⁶ , DB name) C07H 1/00-23/00 WPI (DIALOG) CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] (1) General formula Wherein ^one of R ¹ and R ⁴ is a hydrogen atom,
A group having (O) (OH) ₂ or a protecting group for a hydroxyl group is shown, and the other group is a group having formula -P (O) (OH) ₂ . R ² represents a halogen atom, a hydroxyl group or an aliphatic acyloxy group having 6 to 20 carbon atoms, which may have 6 to 20 carbon atoms.
R ³ represents a halogen atom and a hydroxyl group or an aliphatic acyl group having 6 to 20 carbon atoms having a hydroxyl group or an aliphatic acyloxy group having 6 to 20 carbon atoms, or a halogen atom, a hydroxyl group or a carbon atom; It represents an alkyl group having 6 to 20 carbon atoms which may have 6 to 20 aliphatic acyloxy groups. R ⁵ represents a hydrogen atom or a protecting group for a hydroxyl group] and a salt thereof. 2. The method according to claim 1, wherein R ² is a halogen atom,
A hydroxyl group or an aliphatic acyl group having 6 to 20 carbon atoms which may have an aliphatic acyloxy group having 6 to 20 carbon atoms, wherein R ³ is a halogen atom, a hydroxyl group or a 6 to 20 carbon atom; A compound having an aliphatic acyloxy group having 6 to 20 carbon atoms and a salt thereof. 3. The method according to claim 1, wherein R ² is a halogen atom,
A hydroxyl group or an aliphatic acyl group having 6 to 20 carbon atoms which may have an aliphatic acyloxy group having 6 to 20 carbon atoms, wherein R ³ is a halogen atom, a hydroxyl group or a 6 to 20 carbon atoms; A compound having an alkyl group having 6 to 20 carbon atoms which may have an aliphatic acyloxy group, and a salt thereof.