JPH0832714B2 - New disaccharide derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial field of application> The present invention provides compounds of formula (I) [In the formula, Z represents an alkylene group having 1 to 9 carbon atoms. R represents a carboxyl group or a phosphonoxy group. R ¹ , R ² , R ³ and R ⁴ each independently represent a linear or branched acyl group having 2 to 60 carbon atoms, wherein the acyl group is a hydroxyl group or 2 to 30 carbon atoms.
It may have an acyloxy group. R ⁵ , R ⁶ and R ⁷ each independently represent a hydrogen atom or a phosphono group. ] The compound and its salt represented by these.

The compound of formula (I) has excellent antitumor activity and low toxicity. Therefore, the compound of formula (I) is useful as a medicine.

<Prior Art> Natural lipid A has a mitogenic activity, that is, an action of stimulating lymphocytes, blasting them to promote the increase of lymphoid cells and enhancing immune function, and a tumor necrosis factor-inducing action. Therefore, it is promising as a prophylactic / therapeutic agent and an antitumor agent for many diseases caused by reduced immune function, such as various infectious diseases.

As a derivative of the above natural lipid A, 2-deoxy-
6-0- {2-deoxy-2-[(R) -3-dodecanoyloxytetradecanoylamino] -4-0-phosphono-3-0-[(R) -3-tetradecanoyloxytetradeca Noyl] -β-D-glucopyranosyl} -3-
0-[(R) -3-hydroxytetradecanoyl] -2
-[(R) -3-Hydroxytetradecanoylamino]
-1-0-phosphono-α-D-glucopyranose (JP-A-61-53295, hereinafter, compound A) is known. The compound is known to have an activity equal to or higher than the physiological activity of natural lipid A (Eur. J. Biochem., 148 ).
1-5,1985) is as toxic as natural lipid A,
Not in practical use. Therefore, a compound having useful physiological activity and reduced toxicity is desired.

<Problems to be Solved by the Invention> The present inventors have completed the present invention as a result of extensive studies to solve the above problems.

<Structure of the Invention> The present invention relates to a compound of formula (I) and a salt thereof, and a compound of formula (II)
Of compounds.

 The substituents of the compound of formula (I) are described below.

Examples of the alkylene group include methylene, ethylene, propylene, butylene, amylene, hexylene and the like, preferably methylene, ethylene, propylene and the like having 1 to 1 carbon atoms.
I can give you three.

Examples of the acyl group include acetyl, propanoyl, isopentanoyl, hexanoyl, decanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, octadecanoyl, eicosanoyl, docosanoyl, tricosanoyl, tetracosanoyl, pentacosanoyl, octacosanoyl. , Triacontanoyl, dotriacontanoyl, hexatriacontanoyl, octatriacontanoyl, 2-pentenoyl, 12-tridecenoyl, 13-docosenoyl, 15-tetracosenoyl, 9,12-octadecadienoyl, 4,8,12 , 15,19
-Docosapentaenoyl and the like can be mentioned. With regard to the substituents R ^{1 to} R ⁴ , an acyl group having 10 to 20 carbon atoms can be mentioned as a preferable one. As the acyloxy group which the acyl group may have, those having 2 to 16 carbon atoms can be mentioned as preferable ones. In addition, R _{1 to} R ₄
When the acyl group of 1 has a hydroxyl group or an acyloxy group, it is preferable to have the above-mentioned substituent at the 2 to 5 position of the acyl group.

Regarding the compound of formula (I), α and β isomers are known with respect to the configuration at the 1-position of sugar, but in the present invention, either one or both may be used, or a mixture thereof may be used. Further, when the acyl group of R _{1 to} R ₄ has the above-mentioned substituent, isomers having R and S configurations exist, but in the present invention, each isomer and a mixture thereof are included.

Examples of the salt of the compound of the formula (I) include salts of a phosphoric acid group or a carboxyl group with an organic amine such as triethylamine, pyridine and N-methylamine or an inorganic base such as ammonia, sodium, potassium, calcium and magnesium. You can

The compound of the present invention can be synthesized by various methods, and one example is shown below.

[In the formula, Z, R, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are the same as described above. R ⁸ , R ⁹ , R ¹⁰ and R ¹¹ each independently have 2 to 2 carbon atoms.
60 acyl groups are shown, and the acyl group may have a hydroxyl group which may be protected or an acyloxy group having 2 to 30 carbon atoms. Q represents COOR ¹⁴ or OPO (OR ¹⁵ ) ₂ . R ¹² and R ¹⁶ each independently represent a hydrogen atom or PO (OR ¹⁵ ) ₂ . R ¹³ is PO
(OR ¹⁵ ) ₂ or a hydroxyl-protecting group. R ¹⁴ represents a protecting group for a carboxyl group, and R ¹⁵ represents a protecting group for a phosphono group. ] The protecting group in the above formula will be further described.

Examples of the protective group for the carboxyl group include a benzyl group which may have a substituent such as a halogen atom, a nitro group and a lower alkoxy group. Examples of the protecting group for the phosphono group include a phenyl group and a benzyl group which may have a substituent such as a halogen atom, a nitro group and a lower alkoxy group. Examples of the hydroxyl-protecting group include a benzyl group which may have a substituent such as a halogen atom, a nitro group and a lower alkoxy group, a trichloroethoxycarbonyl group and a trichlorotertiary butoxycarbonyl group.

 Next, each step will be described below.

First step Dissolve the compound of formula (III) in a solvent that does not participate in the reaction, including hydrogen bromide gas, for example, a single or mixed solvent such as methylene chloride, acetic acid, etc. By reacting, the sugar 1-position acetyl group of the present compound can be replaced with bromine. The bromine substitution product obtained is dissolved in a dry organic solvent, preferably methylene chloride, chloroform or the like, and the presence of mercuric cyanide, mercuric bromide, silver carbonate, silver oxide, silver perchlorate or mercuric nitrate is present. Or a mixture of these and a dehydrating agent such as anhydrous calcium sulfate
The compound of formula (IV) can be obtained by condensation with the compound of I) for several hours to 2 days under reaction conditions such as room temperature to reflux.

Second step A route Compound of formula (IV) is dissolved or suspended in acetic acid, zinc powder is added, and the mixture is treated at room temperature for about several tens of minutes to 24 hours to remove the protecting group of amino group at 2'position. Later, fatty acid condensation methods commonly used in the field of peptide chemistry, such as the carbodiimide method,
The compound of formula (VI) can be obtained by condensation using the Eintop method, the active ester method or the like.

B route The compound of formula (IV) is dissolved in a dry organic solvent, preferably methylene chloride, chloroform, acetonitrile, tetrahydrofuran, etc., The compound of formula (V) can be obtained by reacting with (in the formula, X represents a halogen atom and R ¹⁵ is the same as above) at room temperature for about 1 to 24 hours.

The reaction may be carried out in the presence of pyridine, 4-dimethylaminopyridine or the like in the reaction system. The compound of formula (VI) can be obtained by subjecting the obtained compound of formula (V) to reaction treatment according to the method described in Route A.

Third step Catalytic reduction of the compound of formula (VI) using tetrahydrofuran, methanol, ethanol, acetic acid, water, etc. alone or in a mixed solvent under hydrogen gas atmosphere using palladium black, palladium carbon, platinum dioxide catalyst, etc. The compound of the present invention can be obtained by removing the groups all at once, purifying by silica gel column chromatography or the like, if necessary, and then appropriately desalting by an electrodialysis method, an acid precipitation method, or an ion exchange resin method.

Further, the salt of the compound of the present invention and a base can be obtained by adding a necessary amount of a base by an appropriate method such as a precipitation method or a freeze-drying method.

The starting compound of formula (III) can be produced by the method described in JP-A-61-53295 or a method analogous thereto.

The starting compound of formula (II) can be produced by the method shown below.

[Wherein X, Z, Q, R ⁸ and R ⁹ are the same as described above, and Z ¹ , Z ² , Z
³ and Z ⁴ each independently represent a lower acyl group, and Z ⁵
Means alkylidene or allylidene, Y means Z ¹ , trichloroethoxycarbonyl or trichlorotertiary butoxycarbonyl, W ¹ is OW ⁴ or COOW ⁵ (wherein W ⁴ is lower acyl, benzoyl, benzyl or p -Chlorobenzyl, W ⁵ is lower alkyl, benzyl or p-chlorobenzyl, and W ² is OW ⁶ or COOW ⁷ (in the formula, W ⁶
Represents a hydrogen atom, benzyl or p-chlorobenzyl, and W ⁷ represents benzyl or p-chlorobenzyl. ),
W ³ is COOW ⁷ , OW ⁷ or (In the formula, W ⁷ and R ¹⁵ are the same as the above.). The compound (XI) can be produced by applying a method commonly used in the field of sugar chemistry. For example compound (VII) and HOZW ¹
Oxazoline-mediated method of condensing benzene in the presence of Lewis acid, saccharides (IX) and HOZW ¹ with mercuric cyanide, silver carbonate,
The König-Knorr method of condensing silver oxide, mercury bromide, silver perchlorate, mercuric nitrate, etc. alone or in the presence of a mixture thereof, or compound (X) and HOZOH with hydrogen chloride, p-toluenesulfonic acid, etc. Compound (XI) can be produced by condensing using a Fischer's method of reacting in the presence of an acid and then acylating a hydroxyl group.

When Y of the obtained compound (XI) is an acyl group such as acetyl, it is a Meyerbain reagent, and when Y is a trichloroethoxycarbonyl, trichlorotertiary butoxycarbonyl group, etc., the zinc powder is converted to an acid such as hydrochloric acid or acetic acid. Using a free amino group at the 2-position of the sugar in the presence of the fatty acid, and a condensation method commonly used in the field of peptide chemistry for the fatty acid represented by the formula R ⁸ OH, such as acid chloride method, carbodiimide method, eintop method or active ester method. The compound (XII) can be obtained by condensation by condensation.

The compound (XIII) can be obtained by eliminating the acyl group of the hydroxyl group of the obtained compound (XII) by a conventional method.

However, due to the deprotection of the acyl group of compound (XII), W ²
When becomes COOH, the compound (XIII) can be obtained by reacting with XW ^{7 in the} presence of an organic amine such as triethylamine. Then, the sugar 4 of the obtained compound (XIII)
The compound (X IV) can be obtained by protecting the 6- and 6-position hydroxyl groups with alkylidene, arylidene, etc., which are commonly used in the field of synthetic chemistry of sugars.

When W ^{2 of the} compound (X IV) is a compound represented by the formula OW ⁶ (however, W ⁶ is not a hydrogen atom) or a compound represented by the formula COOW ⁷ , R
^A compound (X) is introduced by introducing a fatty acid represented by ⁹ OH at the 3-position of the sugar using the acid chloride method, the carbodiimide method, or the like.
V) can be obtained.

When W ^{2 of the} compound (X IV) is represented by OH, in the presence of organic amines such as triethylamine, 4-dimethylaminopyridine and pyridine, Compound (XV) can be obtained by condensation reaction with fatty acid R ⁹ OH in the same manner as above after condensation reaction with.

W ³ of the compound (XV) has the formula COOW ⁷ or In the case represented by, the protective group Z ⁵ should be eliminated by hydrolysis in water-containing acetic acid such as 50-90% acetic acid aqueous solution (v / v%) for about 10 minutes to several hours at about 50-100 ° C. The compound of formula (II) can be produced by

In addition, when W ^{3 of} the compound (XV) is the formula OW ⁷ , W ⁷ is eliminated by catalytic reduction and the resulting primary alcohol residue is formed. The compound of the formula (II) can be similarly prepared by condensing the compound in the presence of an organic amine and then removing Z ⁵ under the same conditions as above.

<Effect of the Invention> The compound of the present invention has low toxicity and shows an excellent antitumor effect. Therefore, the compound of the present invention is useful for the prevention and treatment of tumors. The compound of formula (II) is important as a synthetic intermediate for the compound of formula (I).

Hereinafter, the present invention will be further described with reference to Reference Examples, Examples and Test Examples, but the present invention is not limited thereto.

Reference Example 1 Step 1 2-acetoxyethyl 3,4,6-tri-0-acetyl-2-deoxy-2- (2,2,2-trichloroethoxycarbonylamino) -α-D-glucopyranoside 5.00 g of 2- To deoxy-2- (2,2,2-trichloroethoxycarbonylamino) -D-glucose (hereinafter compound B), 5.0 ml of ethylene glycol and 0.5 ml of dioxane containing hydrogen chloride gas were added and heated to 90 ° C. And stir for 4 hours. The reaction mixture was ice-cooled, 75 ml of pyridine was added, and 30.6
Add g acetic anhydride and stir. After 20 minutes, return to room temperature and further 1
Stir for 6 hours. The reaction solution is poured into 350 ml of ice water and stirred, and the precipitated solid is filtered and washed with water.

The solid obtained is dissolved in chloroform, washed successively with 1N hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was recrystallized from ethanol to obtain 4.96 g of the title compound as colorless prism-like crystals.

Melting point 138 to 140 ° C ▲ [α] ²⁵ _D ▼ + 74.0 ° (C1.2, chloroform) Step 2 2-acetoxyethyl 3,4,6-tri-0-acetyl-2-deoxy-2-tetradecanoyl Amino-
α-D-Glucopyranoside 4.96 g of the compound obtained in Step 1 is dissolved in 60 ml of acetic acid, 7 g of zinc powder is added little by little while stirring at room temperature, and the mixture is stirred for 1 hour. The insoluble matter is filtered off, the solvent is distilled off under reduced pressure, toluene is added to the obtained residue, and the solvent is distilled off under reduced pressure again. The obtained residue is dissolved in dioxane, dioxane containing hydrogen chloride gas is added, the solvent is distilled off under reduced pressure, and then dried.

Dissolve the resulting oil in 70 ml of anhydrous methylene chloride,
Under ice cooling, 2.88 ml of N-methylmorpholine and 3.24 g of tetradecanoic acid chloride were added and the mixture was stirred for 1 hour. Add 10 ml of methanol, stir at room temperature for 10 minutes, dilute with chloroform, and wash successively with 1N hydrochloric acid and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was filtered through a silica gel column [eluting solvent: a mixture of benzene and ethyl acetate (initially 9/1 (v / v) ratio, then 1/1 (Change to (v / v))] to give 4.77 g of the title compound as a colorless oil.

Step 3 2-hydroxyethyl 2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside 4.77 g of the compound obtained in Step 2 was dissolved in 80 ml of anhydrous methanol, and 9 mmol of sodium methylate methanol was added under ice cooling. Add the solution and stir for 30 minutes at room temperature. Tetrahydrofuran is added to dissolve the precipitated insoluble matter, which is then neutralized with a strongly acidic ion exchange resin Dowex-50 (H ⁺ type), and the resin is removed by filtration. The solvent of the filtrate was distilled off under reduced pressure and the residue obtained was washed with ether and collected by filtration to obtain the title compound 3.
02 g are obtained as a white solid. Recrystallized with ethanol-water. Melting point 158 to 160 ° C ▲ [α] ²⁵ _D ▼ + 82.1 ° (C0.8, tetrahydrofuran: water = 4: 1, v / v).

Step 4 2-hydroxyethyl 2-deoxy-4,6-
0-isopropylidene-2-tetradecanoylamino-
α-D-glucopyranoside 0.87 g of the compound obtained in Step 3 was dissolved in 20 ml of dimethylformamide, and 0.62 g of 2,2-dimethoxypropane and 38 mg of p-toluenesulfonic acid monohydrate were added at room temperature,
Stir for 1.5 hours. Neutralize with a 5% aqueous sodium hydrogen carbonate solution and evaporate the solvent under reduced pressure. The residue is dissolved in ethyl acetate, washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was applied to a silica gel column [elution solvent: first a mixed solution of chloroform and acetone 19/1, (v / v) and then a mixed solution of chloroform and methanol 19/1, (v / v). Change] to the title compound
0.78 g is obtained as a colorless viscous oil.

Step 5 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-4,6-0-isopropylidene-2-tetradecanoylamino-α-D-glucopyranoside (hereinafter, compound C) 0.77 g of the compound obtained in step 4 was dissolved in 15 ml of anhydrous methylene chloride and cooled to 0.48 under ice cooling. Add g diphenylphosphorochloridate, 0.19 ml pyridine and 0.30 g dimethylaminopyridine and stir for 1 hour. After returning to room temperature and stirring for 1 hour, 0.17 g of diphenylphosphorochloridate was added,
Stir for minutes. Add 3 ml of methanol to the reaction mixture, stir for a while, and evaporate the solvent under reduced pressure. The residue is purified by silica gel column (eluting solvent: chloroform: acetone = 19: 1, v / v) to obtain 0.81 g of the title compound as a colorless viscous oil.

Step 6 2- (diphenylphosphonoxy) ethyl 2-
Deoxy-3-0-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 0.81 g of the compound obtained in Step 5 was dissolved in 10 ml of anhydrous methylene chloride, and 0.45 ml of pyridine and 0.45 g of ice-cooled solution were added. Add tetradecanoic acid chloride, 50 mg of dimethylaminopyridine,
Cool on ice for 30 minutes, then return to room temperature and stir for 30 minutes. 2m
Add 1 l of methanol, stir for a while, dilute with chloroform, wash with 1N hydrochloric acid, water, and saturated saline solution in that order, and dry over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure and the obtained residue is dissolved in 30 ml of 90% acetic acid aqueous solution and stirred for 40 minutes while heating at 90 ° C. The solvent was distilled off under reduced pressure, toluene was added to the residue, and the solvent was distilled off under reduced pressure twice. ) And then change to a mixed solution of chloroform and methanol (19/1, v / v)] to obtain 0.92 g of the title compound as a colorless foamy semi-solid.

▲ [α] ²⁵ _D ▼ + 40.8 ° (C1.1, chloroform) Reference Example 2 Step 1 2-acetoxyethyl 3,4,6-tri-0-acetyl-2-[(R) -3-benzyloxy Tetradecanoylamino] -2-deoxy-α-D-glucopyranoside 3.00 g of the compound obtained in Step 1 of Reference Example 1 was dissolved in 40 ml of acetic acid, 3.0 g of zinc powder was added with stirring at room temperature, and the mixture was stirred for 1 hour. To do. Insoluble matter is removed by filtration, washed with chloroform, and the solvent is distilled off under reduced pressure. Repeat the procedure of adding toluene to the residue and distilling off the solvent, then dissolve in chloroform and add 5%
Wash with aqueous sodium hydrogen carbonate solution and dry over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure to obtain an oily substance. On the other hand, 1.95 g of (R) -3-benzyloxytetradecanoic acid was dissolved in 30 ml of anhydrous tetrahydrofuran and cooled to 0.98 under ice cooling.
Add 1 g of 1-hydroxybenzotriazole and 1.32 g of dicyclohexylcarbodiimide, return to room temperature, and stir for 3 hours. The precipitated crystals were removed by filtration, the filtrate and the above oily substance were mixed under ice cooling, 0.70 ml of N-methylmorpholine was added, the temperature was returned to room temperature, and the mixture was stirred for 3 hours. The residue obtained by distilling off the solvent under reduced pressure was applied to a silica gel column [elution solvent: a mixture of chloroform and acetone (initially 96/4 (v / v) and then 92/8
(Change to v / v))] to obtain 3.70 g of the title compound.

NMR (CDCl ₃ ), δ (ppm): 0.87 (3H, t, J = 6Hz) 2.00 (3H, s) 2.02 (3H, s) 2.04 (3H, s) 2.08 (3H, s) 2.18 (2H, m ) 4.54 (2H, ABq, J = 12Hz) 4.76 (1H, d, J = 4Hz) 7.36 (5H, s) Step 2 2-hydroxyethyl 2-[(R) -3-benzyloxytetradecanoylamino]- 2-Deoxy-α-D-glucopyranoside The compound obtained in Step 1 is treated in the same manner as in Step 3 of Reference Example 1 to obtain the title compound as a pale brown powder. Water −
Recrystallized from ethanol. Melting point 125 to 127 ° C ▲ [α] ²⁵ _D ▼ + 73.3 ° (C0.9, methanol) Step 3 2-hydroxyethyl 2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy- 4,6-0-Isopropylidene-α-D-glucopyranoside The compound obtained in Step 2 is reacted in the same manner as in Step 4 of Reference Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 31.4 ° (C0.9, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.89 (3H, t, J = 6Hz) 1.45 (3H, s) 1.56 (3H, s ) 2.50 (2H, m) 4.20 (1H, m) 4.57 (2H, ABq, J = 12Hz) 4.70 (1H, d, J = 4Hz) 7.40 (5H, s) Step 4 2- (Diphenylphosphonoxy) ethyl 2-
[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-4,6-0-isopropylidene-α
-D-Glucopyranoside (hereinafter referred to as Compound D) The compound obtained in Step 3 is reacted in the same manner as in Step 5 of Reference Example 1 to obtain the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.88 (3H, t, J = 7Hz) 1.46 (3H, s) 1.53 (3H, s) 2.47 (2H, d, J = 6Hz) 4.2 (3H, m) 4.53 (2H, ABq, J = 12Hz) 4.64 (1H, d, J = 4Hz) 7.2-7.4 (15H, m) Step 5 2- (Diphenylphosphonoxy) ethyl 3-
0-[(R) -3-benzyloxytetradecanoyl]
2-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-α-D-glucopyranoside The compound obtained in Step 4 (0.96 g) and 0.59 g of (R) -3-benzyloxytetradecanoic acid were Dissolve in 10 ml of anhydrous methylene chloride, and under ice cooling, 30 mg of dimethylaminopyridine and 0.39 g
After adding dicyclohexylcarbodiimide in 15 minutes and returning to room temperature, stir overnight. The precipitated crystals are removed by filtration, the filtrate is washed successively with 0.2N hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure
Dissolve in 30 ml of 90% acetic acid aqueous solution (v / v) and heat to 90 ℃
Stir for 30 minutes. The solvent was distilled off under reduced pressure, toluene was added to the residue and the solvent was distilled off under reduced pressure. The residue obtained was repeated on a silica gel column [elution solvent: first a mixture of chloroform and acetone (19/1, v / v) And later changed to a mixed solution of chloroform and methanol (19/1, v / v)]
1.23 g of the title compound are obtained as a colorless oil.

▲ [α] ²⁵ _D ▼ + 31.4 ° (C1.2, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (6H, t, J = 7Hz) 2.34 (2H, d, J = 6Hz) 2.4 To 2.7 (2H, m) 4.51 (2H, ABq, J = 12Hz) 4.56 (2H, s) 4.71 (1H, d, J = 4Hz) 5.13 (1H, m) 7.2 to 7.4 (20H, m) Reference Example 3 Step 1 2-benzyloxyethyl 2-acetamide-
3,4,6-Tri-0-acetyl-2-deoxy-β-D-
Glucopyranoside 8.2 g of anhydrous calcium sulfate was suspended in 90 ml of anhydrous methylene chloride, 3.79 ml of boron trifluoride ether complex was added, and the mixture was stirred at room temperature for 15 minutes, and then 7.78 g of 2-acetamide-1,3,4,6. -Tetra-0-acetyl-2-deoxy-
β-D-glucopyranose (hereinafter, compound E) was added,
Stir at room temperature. 1.26 ml of boron trifluoride ether complex was added on the way, and after stirring for 19 hours, the reaction solution was poured into about 5% sodium hydrogen carbonate aqueous solution to be neutralized and extracted with chloroform. The extract is washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent is evaporated under reduced pressure. 90m of the residue obtained and 6.09g of 2-benzyloxyethanol
Dissolve in 1 l anhydrous chloroform, add 190 mg p-toluenesulfonic acid hydrate, and heat to reflux for 6.5 hours. The reaction mixture is washed successively with 5% aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was applied to a silica gel column [eluting solvent: a mixture of chloroform and acetone (the ratio was 19/1 (v / v) at the beginning and later changed to 7/1 (v / v))]. Purify and wash with ether to give 3.60 g of the title compound as a white powder. Recrystallize with methanol-water. Melting point 106-107 ° C. [α] ²⁵ _D ▼ -17.0 ° (C1.2, chloroform) Step 2 2-benzyloxyethyl 3,4,6-tri-0
-Acetyl-2-deoxy-2-tetradecanoylamide-β-D-glucopyranoside 1.50 g of the compound obtained in step 1 was dissolved in 30 ml of anhydrous methylene chloride, 1.55 g of anhydrous potassium carbonate was suspended, and 1.18 g of Triethyloxonium tetrafluoroborate is dissolved in anhydrous methylene chloride and added, and the mixture is stirred at room temperature for 17.5 hours.
The reaction solution is washed successively with water and saturated brine and dried over anhydrous sodium sulfate. 30 ml of the residue obtained by distilling off the solvent under reduced pressure
Dissolved in tetrahydrofuran, 3.2 ml of 1N hydrochloric acid is added under ice cooling, and the mixture is stirred at room temperature for 40 minutes. The solvent is distilled off under reduced pressure, benzene is added to the residue, and the solvent is distilled off under reduced pressure. The obtained residue is dissolved in 30 ml of anhydrous methylene chloride, 0.92 g of tetradecanoic acid chloride and 1.02 ml of N-methylmorpholine are added under ice cooling, and the mixture is stirred under ice cooling for 1 hour.
After adding 5 ml of methanol to the reaction solution and returning to room temperature and stirring for a while, the reaction solution is washed successively with 1N hydrochloric acid and saturated saline. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column [eluting solvent: chloroform: acetone = 19: 1 (v / v)] to give 1.11 g of the title compound as white Obtained as a powder. Recrystallize from n-hexane and benzene. Melting point 101-102 ° C ▲ [α] ²⁵ _D ▼ -5.4 ° (C0.9, chloroform) Step 3 2-benzyloxyethyl 2-deoxy-2
-Tetradecanoylamino-β-D-glucopyranoside The compound obtained in Step 2 is treated in the same manner as in Step 3 of Reference Example 1 to obtain the title compound as a white powder. Recrystallize from ethanol-water. Melting point 155 to 156 ° C ▲ [α] ²⁵ _D ▼ -18.1 ° (C0.5, methanol) Step 4 2-benzyloxyethyl 2-deoxy-4,
6-0-Isopropylidene-2-tetradecanoylamino-β-D-glucopyranoside 710 mg of the compound obtained in Step 3 was suspended in 30 ml of anhydrous methylene chloride, and 0.42 g of 2,2-dimethoxypropane was added at room temperature.
Add 25 mg of p-toluenesulfonic acid monohydrate and stir for 1.5 hours. The reaction mixture is washed with 5% aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure, and the residue is purified by a silica gel column [eluting solvent: chloroform: acetone = 9: 1 (v / v)] to obtain 710 mg of the title compound as a waxy solid.

Step 5 2-benzyloxyethyl 2-deoxy-4,
6-0-Isopropylidene-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranoside 700 mg of the compound obtained in step 4 was dissolved in 10 ml of anhydrous methylene chloride, and 0.49 ml of pyridine under ice cooling. And 0.46 g of tetradecanoic acid chloride and 50 mg of dimethylaminopyridine are added, and after 20 minutes, the temperature is returned to room temperature and stirred for 40 minutes. After adding 2 ml of methanol and stirring for a while, the solvent was distilled off under reduced pressure, and the residue was applied to a silica gel column [elution solvent: a mixed solution of benzene and ethyl acetate (initially 19/1 (v / v) and later 4/1 (v / v ))) To obtain 790 mg of the title compound as a white powder.
Melting point 88-90 ° C ▲ [α] ²⁵ _D ▼ -29.0 ° (C0.8, chloroform) Step 6 2-hydroxyethyl 2-deoxy-4,6-
0-isopropylidene-3-0-tetradecanoyl-2
-Tetradecanoylamino-β-D-glucopyranoside 745 mg of the compound obtained in Step 5 was suspended in 50 ml of acetic acid,
Add 4 g of 5% palladium carbon and stir for 15 hours under a hydrogen stream. Precipitated crystals and catalyst are removed by filtration, and the filtrate is freeze-dried to obtain a powder. The insoluble matter on the filter paper is washed with chloroform to dissolve the crystals, and only the catalyst is removed by filtration. This washing solution and the above lyophilized powder in chloroform solution are combined, washed with a 5% aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was a silica gel column [eluting solvent: chloroform: acetone = 19: 1 (v / v)].
Purify in 5 to obtain 529 mg of the title compound as a white powder.

Step 7 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranoside The compound (515 mg) obtained in step 6 was dissolved in 15 ml of anhydrous methylene chloride, and 0.09 ml of pyridine and 304 mg of diphenylphosphoric acid were dissolved under ice cooling. Add rochloridate and 138 mg of dimethylaminopyridine, return to room temperature and stir for 16 hours. Add 2 ml of methanol to the reaction mixture, stir for a while, dilute with chloroform, and wash with 1N hydrochloric acid and saturated brine successively. After drying over anhydrous sodium sulfate, the solvent is distilled off under reduced pressure. Dissolve the obtained residue in 25 ml of 90% acetic acid aqueous solution and heat to 90 ° C to
Stir for minutes. After distilling off the solvent under reduced pressure, adding toluene to the residue and distilling off the solvent under reduced pressure, the residue was replaced by a silica gel column [eluting solvent: initially chloroform and acetone mixture (19/1, v / v). After that, it was purified by a mixed solution of chloroform and methanol (19/1, v / v)] to obtain 491 mg of the title compound as a colorless caramel oil.

▲ [α] ²⁵ _D ▼ -19.5 ° (C0.9, chloroform) Reference Example 4 Step 1 Benzyloxycarbonylmethyl 2-acetamide-3,4,6-tri-0-acetyl-2-deoxy-β
-D-Glucopyranoside Compound E 3.89 g was treated with glycolic acid benzyl ester in the same manner as in Step 1 of Reference Example 3 to obtain the title compound as a powder. Recrystallization of this powder from benzene-hexane gives 2.18 g of colorless crystals. Melting point 138 to 143 ° C ▲ [α] ²⁵ _D ▼ -35.8 ° (C1.1, chloroform) Step 2 Benzyloxycarbonylmethyl 3,4,6-tri-0-acetyl-2-[(R) -3-benzyl Oxytetradecanoylamino] -2-deoxy-β-D-glucopyranoside 1.00 g of the compound obtained in step 1 was dissolved in 30 ml of anhydrous methylene chloride, 1.00 g of anhydrous potassium carbonate was suspended, and 0.57 g of triethyloxonium was added. Dissolve tetrafluoroborate in anhydrous methylene chloride, add, and stir at room temperature for 18 hours. The reaction solution is washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent is evaporated under reduced pressure to give an oil. Dissolve this oil in 25 ml of tetrahydrofuran and add 2.0 ml of 1
Add normal hydrochloric acid and stir at room temperature for 30 minutes. The solvent is dried under reduced pressure, benzene is further added, and the procedure of distilling off under reduced pressure is repeated, followed by drying under reduced pressure to obtain a pale brown powder. On the other hand, 0.80g
(R) -3-Benzyloxytetradecanoic acid (1) was dissolved in 20 ml of anhydrous tetrahydrofuran, 0.38 g of 1-hydroxybenzotriazole was added, and the mixture was stirred at room temperature. The reaction solution is once ice-cooled, 0.52 g of dicyclohexylcarbodiimide is added and dissolved, and then the mixture is returned to room temperature and stirred for 3 hours. Precipitated crystals are removed by filtration, the filtrate and a tetrahydrofuran suspension of the above powder are mixed under ice-cooling, 0.33 ml of N-methylmorpholine is further added, and the mixture is returned to room temperature and stirred for 17 hours.
The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column [eluting solvent: chloroform: acetone = 19: 1 (v / v)] to obtain 1.16 g of the title compound as a white solid. Melting point 104-
110 ° C ▲ [α] ²⁵ _D ▼ -15.9 ° (C1.1, chloroform) NMR (CDCl ₃ ), δ (ppm): 1.26 (s) 1.98 (3H, s) 2.02 (3H, s) 2.08 (3H, s) 4.24 (2H, s) 4.56 (2H, s) 5.16 (2H, s) 7.32 to 7.36 (10H, m) Step 3 Benzyloxycarbonylmethyl 2-
[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-β-D-glucopyranoside 0.77 g of the compound obtained in step 2 was dissolved in 30 ml of tetrahydrofuran, and 4.4 ml of 1N hydroxylated solution was stirred with ice cooling. Add sodium, add 5 ml of water on the way, and stir for 1 hour. After the reaction, add citric acid aqueous solution to make it acidic, and extract with ethyl acetate. The extract is dried over anhydrous sodium sulfate, and the solvent is evaporated under reduced pressure. The residue is dissolved in 10 ml of dimethylformamide, 0.42 ml of triethylamine and 0.34 g of benzyl bromide are added, and the mixture is heated to 50 ° C and stirred for 2 hours. The reaction mixture is diluted with ethyl acetate, washed successively with 2% aqueous citric acid solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure, and the residue is purified by a silica gel column [elution solvent: chloroform: methanol = 19: 1 (v / v)] to obtain 0.51 g of the title compound as a white waxy solid. Water −
Recrystallize from methanol. Melting point 128-130 ° C ▲ [α] ²⁵ _D ▼ -37.2 ° (C0.9, chloroform) Step 4 Benzyloxycarbonylmethyl 2-
[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-4,6-0-isopropylidene-β
-D-Glucopyranoside The compound obtained in Step 3 is treated in the same manner as in Step 4 of Reference Example 3 to obtain the title compound as a colorless caramel oil.

NMR (CDCl ₃ ), δ (ppm): 1.26 (s) 1.45 (3H, s) 1.54 (3H, s) 4.22 (2H, ABq) 4.54 (2H, s) 5.18 (2H, s) 7.29 (5H, s) ) 7.36 (5H, s) Step 5 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-4,6-0-isopropylidene-β
-D-Glucopyranoside 146 mg of the compound obtained in Step 4 was dissolved in 4 ml of anhydrous methylene chloride, and 77 mg of (R) -3-benzyloxytetradecanoic acid and 9 mg of 4-dimethylaminopyridine were added and dissolved. Add dicyclohexylcarbodiimide and stir. After dissolution, return to room temperature and stir for 18 hours, then remove the precipitated crystals by filtration. The filtrate is diluted with chloroform and washed successively with 0.1N hydrochloric acid and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was filtered through a silica gel column [elution solvent: mixed solution of benzene and ethyl acetate (initially 19/1 (v / v) ratio, then 9/1 (v / v / Change to v))] to obtain 156 mg of the title compound as a caramel oil. Recrystallized from methanol-water. Melting point 68 ~
70 ° C NMR (CDCl ₃ ), δ (ppm): 1.25 (s) 1.38 (3H, s) 4.19 (2H, s) 4.53 (4H, m) 5.12 (2H, s) 7.30 to 7.34 (15H, m) step 6 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-β-D-glucopyranoside 132 mg of the compound obtained in step 5 was dissolved in 10 ml of 90% acetic acid water and heated to 90 ° C for 30 minutes. Stir. The solvent is distilled off under reduced pressure, benzene is added to the residue, and the solvent is distilled off under reduced pressure to obtain 120 mg of the title compound as a colorless caramel-like solid. Recrystallize from methanol-water. Melting point 95-100
C ▲ [α] ²⁵ _D ▼ -25.6 ° (C1.1, chloroform) Reference Example 5 [Step 1] Methoxycarbonylmethyl 3,4,6-tri-
0-acetyl-2-deoxy-2- (2,2,2-trichloroethoxycarbonylamino) -α-D-glucopyranoside 5.23 g of 1,3,4,6-tetra-0-acetyl-2-deoxy-2 Dissolve-(2,2,2-trichloroethoxycarbonylamino) -D-glucopyranose in 5 ml of methylene chloride, add 15 ml of 25% hydrogen bromide-acetic acid solution, and add 1.5 at room temperature.
Stir for hours. The reaction solution is diluted with chloroform, washed successively with ice water, 5% aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was dissolved in 25 ml of methylene chloride, 5 g of activated calcium sulfate was added, and the mixture was stirred. Under ice-cooling, 3.11 g of anhydrous silver perchlorate was added, followed by 1.80 g of methyl glycolic acid ester, and the mixture was returned to room temperature and stirred for 2 hours.
The insoluble matter is removed by filtration, the filtrate is washed successively with 5% aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was a silica gel column [elution solvent; chloroform: acetone = 19: 1,
(V / v)] and recrystallized from benzene-hexane to obtain 2.74 g of colorless crystals. Melting point 110-111 ° C [α] ²⁵ _D ▼ + 85.6 ° (c0.9, chloroform) [Step 2] Methoxycarbonylmethyl 3,4,6-tri-
0-Acetyl-2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside 1.60 g of the compound obtained in Step 1 was treated with zinc powder in acetic acid and then tetradecanoic acid chloride in the same manner as in Step 2 of Reference Example 1. The reaction is performed to obtain 1.68 g of the title compound as a waxy solid.

▲ [α] ²⁵ _D ▼ + 68.6 ° (c1.2, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.89 (3H, t, J = 7Hz), 2.02 (3H, s), 2.04 (3H , s), 2.11 (3H, s), 2.2 (2H, m), 3.78 (3H, s), 4.90 (1H, d, J = 4Hz), 5.18 (1H, t, J = 10Hz), 5.32 (1H , t, J = 10 Hz) [Step 3] Carboxymethyl 2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside 1.63 g of the compound obtained in Step 2 was dissolved in 20 ml of tetrahydrofuran, and 12.2 ml of ice-cooled water was added. 1N sodium hydroxide solution is added, a small amount of water is further added, and the mixture is stirred for 20 minutes under ice cooling. The reaction solution is neutralized by adding citric acid, and the precipitated crystals are collected by filtration and washed with water. White, light brown powder that dries 1.
Get 16g. Recrystallization from ethanol-water gives colorless crystals.

Melting point 153-156 ° C ▲ [α] ²⁵ _D ▼ + 93.5 ° (c1.0, N, N-dimethylformamide) [Step 4] Benzyloxycarbonylmethyl 2-deoxy-2-tetradecanoylamino-α-D -Glucopyranoside 1.12 g of the compound obtained in Step 3 is dissolved in 20 ml of N, N-dimethylformamide, 0.86 g of benzyl bromide and 0.70 ml of triethylamine are added, and the mixture is heated to 60 ° C and stirred for 2 hours. The reaction solution is diluted with ethyl acetate and washed successively with water and 1N hydrochloric acid. The residue obtained by distilling off the solvent under reduced pressure was applied to a silica gel column [elution solvent; chloroform: methanol = 9: 1 (v /
v)] and washed with n-hexane to give 1.18g of white powder.
Is obtained, and this is recrystallized from ethanol.

Melting point 268-269 ° C ▲ [α] ²⁵ _D ▼ + 82.0 ° (c1.1, N, N-dimethylformamide) [Step 5] Benzyloxycarbonylmethyl 2-deoxy-4,6-0-isopropylidene-2 -Tetradecanoylamino-α-D-glucopyranoside 1.15 g of the compound obtained in Step 4 was reacted in the same manner as in Step 4 of Reference Example 1 to obtain 1.10 g of the title compound as a white powder, which was recrystallized from n-hexane. To do.

Melting point 72-73 ° C ▲ [α] ²⁵ _D ▼ + 35.0 ° (c1.1, chloroform) [Step 6] Benzyloxycarbonylmethyl 2-deoxy-3-0-tetradecanoyl-2-tetradecanoylamino- α-D-Glucopyranoside 1.07 g of the compound obtained in Step 5 was treated with tetradecanoic acid chloride and 90% acetic acid aqueous solution in the same manner as in Step 6 of Reference Example 1 to give 1.24 g of the title compound as a foamy solid. obtain. Recrystallization from n-hexane gives colorless crystals.

Melting point 54-55 ° C ▲ [α] ²⁵ _D ▼ + 46.9 ° (c1.1, chloroform) Reference Example 6 2- (diphenylphosphonoxy) ethyl 2-deoxy-3-0-octanoyl-2-octanoylamino −
α-D-Glucopyranoside Compound B is obtained according to the method of Reference Example 1 as a colorless oil.

▲ [α] ²⁵ _D ▼ + 49.4 ° (c1.2, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.86 (6H, m), 2.08 (2H, t), 2.36 (2H, t), 4.85 (1H, d), 5.10 (1H, m), 7.2 to 7.5 (10H, m) Reference Example 7 2- (diphenylphosphonoxy) ethyl 3-0-decanoyl-2-decanoylamino-2-deoxy- α-
D-Glucopyranoside According to the method of Reference Example 1 from the compound B, the title compound is obtained as a colorless oil.

▲ [α] ²⁵ _D ▼ + 46.1 ° (c0.8, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (6H, t), 2.07 (2H, t), 2.35 (2H, t), 4.85 (1H, d), 5.10 (1H, m), 7.2 to 7.5 (10H, m) Reference Example 8 2- (diphenylphosphonoxy) ethyl 2-deoxy-3-0-dodecanoyl-2-dodecanoylamino-
α-D-Glucopyranoside According to the method of Reference Example 1 from the compound B, the title compound is obtained as a pale yellow oil.

NMR (CDCl ₃ ), δ (ppm): 0.90 (6H, t), 2.07 (2H, t), 2.35 (2H, t), 4.85 (1H, d), 5.10 (1H, m), 7.2 to 7.5 ( 10H, m) Reference Example 9 2- (diphenylphosphonoxy) ethyl 2-deoxy-3-0-hexadecanoyl-2-hexadecanoylamino-α-D-glucopyranoside From Compound B according to the method of Reference Example 1. This gives the title compound as a white powder.

▲ [α] ²⁵ _D ▼ + 37.2 ° (c1.1, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.89 (6H, t), 2.06 (2H, t), 2.32 (2H, t), 4.84 (1H, d), 5.10 (1H, m), 7.2 to 7.5 (10H, m) Reference Example 10 2- (Diphenylphosphonoxy) ethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-Deoxy-2-tetradecanoylamino-α-D-glucopyranoside Compound C is reacted in the same manner as in Step 5 of Reference Example 2 to obtain the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.89 (6H, t), 2.06 (2H, t), 2.1 to 2.8 (2H, m), 4.85 (1H, d), 5.14 (1H, t), 7.1 to 7.3 (15H, m) Reference Example 11 2- (Diphenylphosphonoxy) ethyl 2-
[(R) -3-benzyloxytetradecanoyl] -2
-Deoxy-3-0-tetradecanoyl-α-D-glucopyranoside Compound D was reacted with tetradecanoic acid in the same manner as in Step 5 of Reference Example 2, followed by reaction with a 90% aqueous acetic acid solution to give the title compound. Obtained as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.88 (6H, t), 2.3 to 2.4 (4H, m), 4.52 (2H, d), 4.72 (1H, d), 5.10 (1H, m), 7.2 to 7.5 (15H, m) Reference Example 12 2- (Diphenylphosphonoxy) ethyl 2-
[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -α-D-glucopyranoside Compound D Reference Example 2 (R) -3 in the same manner as in Step 5 of
-Reaction with tetradecanoyloxytetradecanoic acid, followed by treatment with 90% aqueous acetic acid to give the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.88 (9H, t), 2.3 to 2.6 (6H, m), 4.51 (2H, d), 4.72 (1H, d), 7.2 to 7.5 (15H, m) Example 1 Step 1 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-6-0- {2-deoxy-4-0-diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -6-0- (2,2,2- Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 400 mg 1 -0-acetyl-2-deoxy-4-0-
Diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -6-0- (2,2,2
-Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -D-glucopyranose (hereinafter compound F) was dissolved in 1.5 ml of acetic acid, and 5 ml of cooled 25% bromide was added at room temperature. Add hydrogen-acetic acid solution, 2.
Stir for 5 hours. Once ice-cooled, diluted with chloroform,
After washing with ice water, 5% aqueous sodium hydrogencarbonate and saturated brine in that order, dry over anhydrous sodium sulfate. 5 ml of the residue obtained by distilling off the solvent under reduced pressure and 276 mg of the compound obtained in Reference Example 1
Dissolved in anhydrous chloroform, added 0.4 g of activated calcium sulfate and 162 mg of mercuric cyanide, and heated to 70 ° C for 16.5
Stir for hours. The insoluble matter was removed by filtration through Celite, and the filtrate was washed successively with a 5% aqueous potassium iodide solution and saturated saline,
Dry over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was applied to a silica gel column [elution solvent; a mixed solution of benzene and ethyl acetate (the ratio was 9/1 (v / v) at the beginning, and later 2/1).
(Change to (v / v))] to obtain 537 mg of the title compound as an oil.

_{NMR (CDCl 3), δ (} ppm): 0.88 (12H, t, J = 6Hz) 2.07 (2H, t, J = 8Hz) 2.30 (6H, m) 5.63 (1H, m) 7.2~7.4 (20H, m ) Step 2 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-6-0- {2-deoxy-4-0-diphenylphosphono-2-[(R) -3-dodecanoyloxytetradecanoylamino] -3-0-[(R) -3-tetradeca Noyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound 527 mg obtained in Step 1 was dissolved in 8 ml of acetic acid to give 0, 6 g
Suspend the zinc powder in and stir at room temperature for 2.5 hours. Insoluble matter is removed by filtration, washed with chloroform, and the solvent is distilled off under reduced pressure. The residue is dissolved in toluene and the solvent is distilled off under reduced pressure three times. The residue obtained is dissolved in chloroform and washed successively with 1N hydrochloric acid and saturated brine. After drying over anhydrous sodium sulfate, the solvent is distilled off under reduced pressure to obtain a yellow oily substance. On the other hand, 166 mg of (R) -3-dodecanoyloxytetradecanoic acid was dissolved in 3 ml of anhydrous tetrahydrofuran,
61 mg of 1-hydroxybenzotriazole is added, and 91 mg of dicyclohexylcarbodiimide is added under ice cooling and stirred. After 15 minutes, return to room temperature and stir for 3 hours, and remove the precipitated crystals by filtration. This filtrate and a solution of the above oily substance in 10 ml of anhydrous tetrahydrofuran to which 0.07 ml of N-methylmorpholine were added are mixed under ice cooling. After 20 minutes, return to room temperature, 15
Stir for hours. The residue obtained by evaporating the solvent under reduced pressure was applied to a silica gel column [elution solvent; a mixture of benzene and ethyl acetate (the ratio of 4/1 (v / v) was changed to 1/2 (v / v) at the beginning).)
And the title compound (286 mg) is obtained as a caramel oil.

▲ [α] ²⁵ _D ▼ + 13.3 ° (C0.5, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (18H, t, J = 6Hz) 2.03 (2H, m,) 2.3 (10H, m) 5.57 (1H, m) 7.2 to 7.4 (20H, m) Step 3 2-phosphonoxyethyl 2-deoxy-6-
0- {2-deoxy-2-[(R) -3-dodecanoyloxytetradecanoylamino] -4-0-phosphono-
3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-
Tetradecanoyl-2-tetradecanoylamino-α-
D-Glucopyranoside 260 mg of the compound obtained in step 2 was dissolved in 15 ml of tetrahydrofuran, and 290 mg of platinum dioxide was suspended in a stream of hydrogen.
Stir for 22 hours at room temperature. The catalyst is removed by filtration and the solvent is distilled off under reduced pressure. The residue obtained was purified by thin layer chromatography [developed with chloroform: methanol: water = 12: 8: 1 (v / v)] and strongly acidic ion exchange resin Dowex 50 was used.
(H ⁺ type, manufactured by Dow Chemical Co.). A part of the residue obtained by distilling off the solvent under reduced pressure was suspended in dioxane as it was, sonicated, and lyophilized to give 20 mg of the free form of the title compound.
As platinum powder. The rest is dissolved in a 0.1% triethylamine aqueous solution, filtered through a Millipore filter, and then freeze-dried to obtain 36 mg of the triethylamine salt of the title compound as a white powder.

Melting point 163-167 ° C (colored candy-like) ▲ [α] ²⁵ _D ▼ + 15.0 ° (C0.6, chloroform: methanol = 3: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (18H, t,) 1.30 (S) 2.19 (2H, m) 2.30 to 2.40 (8H, m) 2.65 (2H, m) 5.20 (m) Example 2 Step 1 2- (Diphenylphosphonoxy) ethyl 3-
0-[(R) -3-benzyloxytetradecanoyl]
-2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4
-0-diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -6-0-
(2,2,2-trichloroethoxycarbonyl) -2- (2,
2,2-Trichloroethoxycarbonylamino) -β-D
-Glucopyranosyl} -α-D-glucopyranoside Compound F is reacted with the compound obtained in Reference Example 2 in the same manner as in Step 1 of Example 1 to obtain the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.89 (12H, t, J = 7Hz) 2.2 to 2.7 (8H, m,) 5.66 (1H, m) 7.2 to 7.4 (30H, m) Step 2 2- (Diphenyl) Phosphonoxy) ethyl 3-
0-[(R) -3-benzyloxytetradecanoyl]
-2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4
-0-diphenylphosphono-2-[(R) -3-dodecanoyloxytetradecanoylamino] -3-0-
[(R) -3-Tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -α-D-glucopyranoside The compound obtained in Step 1 was treated in the same manner as in Step 2 of Example 1 to give (R) -3. -React with dodecanoyloxytetradecanoic acid to give the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.89 (18H, t, J = 7Hz) 2.2-2.7 (12H, m,) 5.58 (1H, m) 7.2-7.4 (30H, m) Step 3 2-phosphono Xylethyl 2-deoxy-6-
0- {2-deoxy-2-[(R) -3-dodecanoyloxytetradecanoylamino] -4-0-phosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -Β-D-glucopyranosyl} -3-0
-[(R) -3-Hydroxytetradecanoyl] -2-
[(R) -3-Hydroxytetradecanoylamino]-
α-D-glucopyranoside 314 mg of the compound obtained in step 2 was dissolved in 12 ml of acetic acid to give 0.3 g.
5% palladium carbon was added and the mixture was stirred under a hydrogen stream for 6 hours at room temperature. The catalyst is removed by filtration and the solvent is distilled off under reduced pressure. Toluene is added to the residue and the solvent is distilled off under reduced pressure. The resulting residue is purified by a small amount of silica gel column [eluted with chloroform: methanol = 19: 1 (v / v)] to obtain an oily substance. This oily substance is dissolved in 20 ml of tetrahydrofuran, 180 mg of platinum dioxide is added, and the mixture is stirred under a hydrogen stream for 12.5 hours. The reaction solution was filtered, and the residue obtained by distilling the filtrate under reduced pressure was subjected to thin layer chromatography [chloroform: methanol:
Water = 6: 4: 0.7 (v / v) developed] and treated with strong acid ion exchange resin Dowex 50 (H ⁺ type). Add 1% triethylamine methanol solution to the treatment solution and adjust the pH to about 8
After the preparation, the solvent is distilled off under reduced pressure. The obtained residue is 0.
It is dissolved in a 1% aqueous solution of triethylamine, filtered through a Millipore filter, and lyophilized to give 141 mg of the triethylamine salt of the title compound as platinum powder. Part of it is treated again with a strongly acidic ion exchange resin and freeze-dried from dioxane to obtain the title compound as a white powder.

Melting point 144-147 ° C (becomes a candy) ▲ [α] ²⁵ _D ▼ ＋ 9.8 ° (C0.5, chloroform: methanol = 3: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (18H, t,) 2.3 to 2.7 (12H, m) 5.2 (4H, m) Example 3 Step 1 2- (Diphenylphosphonoxy) ethyl 3-
0-[(R) -3-benzyloxytetradecanoyl]
-2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4
-0-diphenylphosphono-6-0- (2,2,2-trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -3-0-[(R) -3-
(2,2,2-Trichloroethoxycarbonyloxy) tetradecanoyl] -β-D-glucopyranosyl} -α-D
-Glucopyranoside 1-0-acetyl-2-deoxy-4-0-diphenylphosphono-6-0- (2,2,2-trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -3-0-[(R) -3- (2,2,2-trichloroethoxycarbonyloxy) tetradecanoyl]
-D-glucopyranose (hereinafter, compound G) was used in Example 1
It is reacted with the compound obtained in Reference Example 2 in the same manner as in Step 1 of 1. to give the title compound as a pale yellow viscous oil.

NMR (CDCl ₃ ), δ (ppm): 0.88 (9H, t, J = 7Hz) 2.3 to 2.7 (6H, m,) 5.70 (1H, m) 7.2 to 7.4 (30H, m) ▲ [α] ²⁵ _D ▼ + 20.2 ° (C0.2, chloroform) Step 2 2- (Diphenylphosphonoxy) ethyl 3-
0-[(R) -3-benzyloxytetradecanoyl]
-2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4
-0-diphenylphosphono-3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-hydroxytetradecanoylamino] -β-D-glucopyranosyl} -α-D -Glucopyranoside The compound obtained in Step 1 is reacted with (R) -3-hydroxytetradecanoic acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 6.3 ° (C0.7, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (12H, t, J = 7Hz) 1.9 to 2.7 (8H, m,) 5.16 ( 1H, m) 5.59 (1H, m) 7.2 to 7.4 (30H, m) Step 3 2-phosphonoxyethyl 2-deoxy-6-
0- {2-deoxy-3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-hydroxytetradecanoylamino] -4-0-phosphono-β-D
-Glucopyranosyl} -3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-hydroxytetradecanoylamino] -α-D-glucopyranoside The compound obtained in step 2 is carried out. Catalytic reduction is performed in the same manner as in Step 3 of Example 2 to obtain the triethylamine salt of the title compound as a white powder. A portion is treated with a strongly acidic ion exchange resin to give the title compound as a white powder.

▲ [α] ²⁵ _D ▼ + 1.8 ° (C0.5, chloroform: methanol = 3: 1 (v / v)) Melting point 155-158 ° C (colors and becomes a candy) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (12H, t,) 2.3 to 2.5 (8H, m) 5.2 (2H, m) Example 4 Step 1 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-6-0- {2-deoxy-4-0-diphenylphosphono-3-0-tetradecanoyl-6-0- (2,
2,2-Trichloroethoxycarbonyl) -2- (2,2,2-
Trichloroethoxycarbonylamino) -β-D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 1-0-acetyl-2-deoxy-4-0-diphenylphosphono -3-0-tetradecanoyl-6-0- (2,
2,2-Trichloroethoxycarbonyl) -2- (2,2,2-
Trichloroethoxycarbonylamino) -D-glucopyranose (hereinafter, compound H) is reacted with the compound obtained in Reference Example 1 in the same manner as in Step 1 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 15.1 ° (C0.8, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.89 (9H, t) 2.0 to 2.5 (6H, m,) 5.06 (1H, t) 5.60 (1H, t) 5.75 (1H, d) 7.2 to 7.5 (20H, m) Step 2 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-6-0- (2-deoxy-4-0-diphenylphosphono-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranosyl) -3-0
-Tetradecanoyl-2-tetradecanoylamino-α
-D-Glucopyranoside The compound obtained in Step 1 is reacted with tetradecanoic acid in the same manner as in Step 2 of Example 1 and recrystallized from methanol to obtain the title compound as a white wax.

Melting point 47 to 50 ° C, ▲ [α] ²⁵ _D ▼ + 5.9 ° (C0.7, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (12H, t) 2.0 to 2.5 (8H, m,) 5.10 (1H, t) 5.50 (1H, t) 5.90 (1H, d) 7.1 to 7.5 (20H, m) Step 3 2-phosphonoxyethyl 2-deoxy-6-
0- (2-deoxy-4-0-phosphono-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-
Glucopyranosyl) -3-0-tetradecanoyl-2-
Tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 1 to obtain the title compound as a white wax.

Melting point 153.5 ° -155.0 ° C (gradually browning and candy-like) ▲ [α] ²⁵ _D ▼ + 13.3 ° (C0.6, chloroform: methanol 9: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (12H) 2.10 to 2.26 (4H, m) 2.26 to 2.46 (4H, m) Example 5 Step 1 2- (Diphenylphosphonoxy) ethyl 2 −
Deoxy-6-0- {2-deoxy-4-0-diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -6-0- (2,2,2- Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranoside Compound F The title compound is obtained as a colorless viscous oil by reacting with the compound obtained in Reference Example 3 in the same manner as in Step 1 of Example 1.

NMR (CDCl ₃ ), δ (ppm): 0.89 (12H, t, J = 7Hz) 2.07 (2H, t, J = 8Hz) 2.22 (2H, t, J = 8Hz) 2.38 (4H, m) 5.23 (1H) , m) 5.58 (1H, t, J = 10Hz) 7.2 to 7.4 (20H, m) Step 2 2- (Diphenylphosphonoxy) ethyl 2-
Deoxy-6-0- {2-deoxy-4-0-diphenylphosphono-2-[(R) -3-dodecanoyloxytetradecanoylamino] -3-0-[(R) -3-tetradeca Noyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranoside The compound obtained in Step 1 was treated in the same manner as in Step 2 of Example 1. Reaction with (R) -3-dodecanoyloxytetradecanoic acid gives the title compound as a colorless viscous oil.

▲ [α] ²⁵ _D ▼ + 16.5 ° (C0.7, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (18H, t, J = 7Hz) 2.05 (2H, m,) 2.3 (10H, m) 5.56 (1H, t, J = 10Hz) 7.2-7.4 (20H, m) Step 3 2-phosphonoxyethyl 2-deoxy-6-
0- {2-deoxy-2-[(R) -3-dotecanoyloxytetradecanoylamino] -4-0-phosphono-
3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-
Tetradecanoyl-2-tetradecanoylamino-β-
D-Glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 1 to obtain the title compound as a white powder, and further the triethylamine salt of the title compound as a white powder.

 The physical properties of the title compound are shown below.

Melting point 145-150 ° C (colors and becomes a candy) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.89 (18H, t) 1.26 (S) 2.3 to 2.5 (8H, m) 2.66 (2H, m) The specific rotation of the above salt is as follows. Show.

▲ [α] ²⁵ _D ▼ + 11.8 ° (C0.5, chloroform: methanol = 3: 1 (v / v)) Example 6 Step 1 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -6-0- (2,2,
2trichloroethoxycarbonyl) -2- (2,2,2trichloroethoxycarbonylamino) -β-D-glucopyranosyl} -β-D-glucopyranoside Compound F was obtained in Reference Example 4 in the same manner as in Step 1 of Example 1. The title compound is obtained as a colorless caramel oil by reacting with the obtained compound.

▲ [α] ²⁵ _D ▼ + 10.1 ° (C1.4, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (12H, t) 1.26 (S) 2.18 to 2.60 (8H, m) 7.2 to 7.4 (25H, m) Step 2 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-2-[(R) -3-dodecanoyloxytetradecanoylamino] -3-0-[(R)
-3-Tetradecanoyloxytetradecanoyl] -β
-D-glucopyranosyl} -β-D-glucopyranoside The compound obtained in Step 1 was reacted with (R) -3-dodecanoyloxytetradecanoic acid in the same manner as in Step 2 of Example 1 to give the title compound as a colorless viscous compound. Obtained as a clear oil.

NMR (CDCl ₃ ), δ (ppm): 0.88 (t) 1.26 (S) 7.2 to 7.38 (m) Step 3 Carboxymethyl 2-deoxy-6-0-
{2-deoxy-2-[(R) -3-dodecanoyloxytetradecanoylamino] -4-0-phosphono-3-
0-[(R) -3-tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-
[(R) -3-Hydroxytetradecanoyl] -2-
[(R) -3-Hydroxytetradecanoylamino]-
β-D-Glucopyranoside 80 mg of the compound obtained in Step 2 was dissolved in 7 ml of tetrahydrofuran, 120 mg of palladium black catalyst was added, and the mixture was placed in a hydrogen atmosphere.
Stir for 24 hours. After removing the catalyst by filtration, 80 mg of platinum dioxide catalyst was added and the mixture was stirred under a hydrogen atmosphere for 4 hours. The catalyst is filtered off, the solvent is distilled off under reduced pressure and the residue obtained is washed with acetonitrile. Then, it was purified by thin layer chromatography (chloroform: methanol: water = 8: 3: 1 (v / v) developed in the lower layer), and the powder obtained was a strongly acidic ion exchange resin (Dowex 50, H ⁺ type). Process. The solvent was distilled off, and the title compound was lyophilized from dioxane.
25 mg are obtained as a white powder.

Melting point 168-172 ° C (colors and becomes a candy) ▲ [α] ²⁵ _D ▼ + 16.1 ° (C0.9, chloroform: methanol = 3: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (t) 1.30 ( S) 2.30 to 2.70 (m) Example 7 Step 1 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -6-0- (2,2,
2-Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranosyl} -4-0-diphenylphosphono-β-D-
Glucopyranoside 1.10 g of the compound obtained in Step 1 of Example 6 was dissolved in 25 ml of anhydrous methylene chloride, 0.20 ml of pyridine, 0.31 g of dimethylaminopyridine and 0.68 g of diphenylphosphorochloridate were added successively, and the mixture was allowed to stand at room temperature for 23 hours. Stir. The reaction mixture is washed successively with 1N hydrochloric acid, water, 5% aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was once passed through a silica gel column [elution solvent; a mixture of benzene and ethyl acetate (the ratio was initially 9/1 (v / v) and was later changed to 4/1 (v / v)). ], And further silica gel column [chloroform: acetone = 19: 1 (v / v)
And develop again to give 580 mg of the title compound as a colorless viscous oil.

Step 2 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-2-[(R) -3-dodecanoyloxytetradecanoylamino] -3-0-[(R)
-3-Tetradecanoyloxytetradecanoyl] -β
-D-glucopyranosyl} -4-0-diphenylphosphono-BD-glucopyranoside The compound obtained in Step 1 was reacted with (R) -3-dodecanoyloxytetradecanoic acid in the same manner as in Step 2 of Example 1. This gives the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.90 (18H, t) 1.26 (S) 7.20 to 7.40 (35H, m) Step 3 Carboxymethyl 2-deoxy-6-0-
{2-deoxy-2-[(R) -3-dodecanoyloxytetradecanoylamino] -4-0-phosphono-3-
0-[(R) -3-tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-
[(R) -3-Hydroxytetradecanoyl] -2-
[(R) -3-Hydroxytetradecanoylamino]-
4-0-phosphono-β-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 6 to obtain the title compound as a white powder.

NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (18H, t) 1.30 (S) 1.20 to 1.70 (m) 2.30 to 2.70 (12H, m) 5.20 (4H, m) Triethylamine salt of this compound The specific optical rotation of is shown below.

▲ [α] ²⁵ _D ▼ 12.4 ° (C0.6, chloroform: methanol = 3: 1 (v / v)) Example 8 Step 1 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4,6-
Bis-0-diphenylphosphono-3-0-[(R) -3
-Tetradecanoyloxytetradecanoyl] -2-
(2,2,2-trichloroethoxycarbonylamino) -β
-D-glucopyranosyl} -β-D-glucopyranoside 1-0-acetyl-2-deoxy-4,6-bis-0-
Diphenylphosphono-3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranose was prepared in the same manner as in Example 1. The title compound is obtained as a colorless caramel oil by reacting with the compound obtained in Reference Example 4 in the same manner as in Step 1.

NMR (CDCl ₃ ), δ (ppm): 0.88 (12H, t) 2.2-2.7 (8H, m) 7.15-7.4 (35H, m) Step 2 Benzyloxycarbonylmethyl 3-0-
[(R) -3-benzyloxytetradecanoyl] -2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4,6-
Bis-0-diphenylphosphono-2-[(R) -3-dodecanoyloxytetradecanoylamino] -3-0-
[(R) -3-Tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -β-D-glucopyranoside The compound obtained in Step 1 was treated with (R) -3-in the same manner as in Step 2 of Example 6. Reaction with dodecanoyloxytetradecanoic acid gives the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.88 (18H, t) 1.24 (S) 2.20 to 2.60 (12H, m) 7.1 to 7.3 (35H, m) Step 3 Carboxymethyl 2-deoxy-6-0-
{2-deoxy-2-[(R) -3-dodecanoyloxytetradecanoylamino] -4,6-0-diphosphono-
3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -β-D-glucopyranosyl} -3-0-
[(R) -3-Hydroxytetradecanoyl] -2
[(R) -3-Hydroxytetradecanoylamino]-
β-D-Glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 6 to obtain the title compound as a white powder.

Melting point 138-145 ° C (colors and becomes a candy) ▲ [α] ²⁵ _D ▼ -9.9 ° (C0.6, chloroform: methanol = 3: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (18H, t) 1.30 (S) 2.30 to 2.70 (12H, m) Example 9 [Step 1] Benzyloxycarbonylmethyl 2-deoxy-6- 0- [2-deoxy-4-0-diphenylphosphono-3-0-tetradecanoyl-6-0- (2,2,2
-Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranosyl] -3-0-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside Compound H In the same manner as in Step 1 of Example 1 and Reference Example 5
Reaction with the compound obtained in step 1 gives the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 18.7 ° (c1.1, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.89 (9H, t, J = 7Hz), 2.16 (4H, m) 2.36 (2H, t, J = 7Hz), 5.13 (1H, t, J = 10Hz) 5.24 (2H, s), 5.56 (1H, t, J = 10Hz) 7.2-7.4 (15H, m) [Step 2] Benzyloxycarbonylmethyl 2-deoxy-6-0- (2-deoxy-4-0-diphenylphosphono-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranosyl) -3-0-tetradecanoyl -2-Tetradecanoylamino-α-D
-Glucopyranoside The compound obtained in Step 1 is reacted with tetradecanoic acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 8.5 ° (c0.9, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (12H, t, J = 6Hz), 2.1 to 2.4 (8H, m), 4.75 (1H, m), 4.84 (1H, d, J = 4Hz), 4.96 (1H, d, J = 8Hz), 5.16 (1H, t, J = 10Hz), 5.22 (2H, s), 5.51 (1H, t, J = 10 Hz), 7.2 to 7.4 (15H, m) [Step 3] Carboxymethyl 2-deoxy-6-0-
(2-deoxy-4-0-phosphono-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranosyl) -3-0-tetradecanoyl-2-tetradecanoylamino-α- D-Glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 6 using a 5% palladium-carbon catalyst and then a platinum dioxide catalyst to give the title compound as a white powder.

Melting point 145-148 ° C (colors and becomes a candy) ▲ [α] ²⁵ _D ▼ + 14.2 ° (c0.5, chloroform: methanol = 3: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD (1: 1)), δ (ppm): 0.90 (12H, t, J = 6Hz), 2.1 to 2.4 (8H, m), 4.80 (1H, d, J = 4Hz), 5.24 (2H, m) Example 10 [Step 1] 2- (diphenylphosphonoxy) ) Ethyl 2
-Deoxy-6-0- [2-deoxy-4-0-diphenylphosphono-3-0-octanoyl-6-0- (2,2,
2-Trichloroethoxycarbonyl) -2- (trichloroethoxycarbonylamino) -β-D-glucopyranosyl] -3-0-octanoyl-2-octanoylamino-α-D-glucopyranoside 1-0-acetyl-2-deoxy- 4-0-diphenylphosphono-3-0-octanoyl-6-0- (2,2,2
-Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -D-glucopyranose was reacted with the compound obtained in Reference Example 6 in the same manner as in Step 1 of Example 1 to give the title compound. The compound is obtained as a colorless oil.

▲ [α] ²⁵ _D ▼ + 18.5 ° (c1.1, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.86 (9H, t), 2.0 to 2.4 (6H, m), 4.68,4.75 (each) 2H, s), 5.04 (1H, t), 5.60 (1H, t), 7.1 to 7.5 (20H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 2
-Deoxy-6-0- (2-deoxy-4-0-diphenylphosphono-3-0-octanoyl-2-octanoylamino-β-D-glucopyranosyl) -3-0-octanoyl-2-octanoylamino -Α-D-Glucopyranoside The compound obtained in Step 1 is reacted with n-caprylic acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 7.6 ° (c1.2, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.86 (12H, t), 2.0 to 2.4 (8H, m), 5.10 (1H, t) ), 5.49 (1H, t), 7.2 to 7.5 (20H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- (2-deoxy-3-0-octanoyl-2-octanoylamino-4-0-phosphono-β-D-glucopyranosyl) -3-0-octanoyl-2-octanoylamino-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 1 to obtain the title compound as a white powder.

Melting point 156-185 ° C (gradually browning and candy-like) ▲ [α] ²⁵ _D ▼ + 16.5 ° (c0.9, chloroform: methanol = 9: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.89 (12H, t), 1.30 (s), 2.10 to 2.45 (8H, m), 5.20 (m) Example 11 [Step 1] 2- ( Diphenylphosphonoxy) ethyl 3
-0-decanoyl-6-0- [3-0-decanoyl-2
-Deoxy-4-0-diphenylphosphono-6-0-
(2,2,2-trichloroethoxycarbonyl) -2- (2,
2,2-Trichloroethoxycarbonylamino) -β-D
-Glucopyranosyl] -2-decanoylamino-2-deoxy-α-D-glucopyranoside 1-0-acetyl-3-0-decanoyl-2-deoxy-4-0-diphenylphosphono-6-0- (2, 2,2-
Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -D-glucopyranose was reacted with the compound obtained in Reference Example 7 in the same manner as in Step 1 of Example 1 to give the title compound. As a colorless oil.

▲ [α] ²⁵ _D ▼ + 16.8 ° (c1.1, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (9H, t), 2.0 to 2.4 (6H, m), 4.68,4.75 (each) 2H, s), 5.05 (1H, t), 5.58 (1H, t), 7.0 to 7.5 (20H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 3
-0-decanoyl-6-0- (3-0-decanoyl-2
-Decanoylamino-2-deoxy-4-0-diphenylphosphono-β-D-glucopyranosyl) -2-decanoylamino-2-deoxy-α-D-glucopyranoside The compound obtained in Step 1 was prepared according to the procedure of Example 1. It is reacted with n-capric acid in the same manner as in Step 2 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 4.8 ° (c1.1, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (12H, t), 2.0 to 2.4 (8H, m), 5.10 (1H, t) ), 5.50 (1H, t), 7.0 to 7.50 (20H, m) [Step 3] 2-phosphonoxyethyl 3-0-decanoyl-6-0- (3-0-decanoyl-2-decanoylamino- 2-deoxy-4-0-phosphono-β-D-glucopyranosyl) -2-decanoylamino-2-deoxy-α-D-glucopyranoside The compound obtained in Step 2 was catalytically reduced in the same manner as in Step 3 of Example 1. To give the title compound as a white powder.

Melting point 148-152 ° C (gradual browning and candy-like appearance) ▲ [α] ²⁵ _D ▼ + 14.5 ° (c0.9, chloroform: methanol = 9: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm) 0.90 (12H, t), 1.30 (s), 2.10 to 2.50 (8H, m), 5.10 to 5.35 (2H, m), Example 12 [Step 1 ] 2- (diphenylphosphonoxy) ethyl 2
-Deoxy-6-0- [2-deoxy-4-0-diphenylphosphono-3-0-dodecanoyl-6-0- (2,2,
2-Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranosyl] -3-0-dodecanoyl-2-dodecanoylamino-α-D-glucopyranoside 1-0- Acetyl-2-deoxy-4-0-diphenylphosphono-3-0-dodecanoyl-6-0- (2,2,2
-Trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -D-glucopyranose was reacted with the compound obtained in Reference Example 8 in the same manner as in Step 1 of Example 1 to give the title compound. Obtained as a colorless oil.

▲ [α] ²⁵ _D ▼ + 17.0 ° (c0.8, chloroform) NMR (CDCl ₃ ), δ (ppm); 0.90 (9H, t), 2.0 to 2.4 (6H, m), 7.2 to 7.5 (20H , m) [Step 2] 2- (diphenylphosphonoxy) ethyl 2
-Deoxy-6-0- (2-deoxy-4-0-diphenylphosphono-3-0-dodecanoyl-2-dodecanoylamino-β-D-glucopyranosyl) -3-0-dodecanoyl-2-dodecanoylamino -Α-D-Glucopyranoside The compound obtained in Step 1 is reacted with lauric acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 4.9 ° (c1.2, chloroform) NMR (CDCl ₃ ), δ (ppm) 0.89 (12H, t), 1.9 to 2.4 (8H, m), 5.10 (1H, t) , 5.50 (1H, t), 7.14 to 7.52 (20H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- (2-deoxy-3-0-dodecanoyl-2-dodecanoylamino-4-0-phosphono-β-D-glucopyranosyl) -3-0-dodecanoyl-2-dodecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 1 to obtain the title compound as a white powder.

Melting point 156-185 ° C (gradual browning and candy-like appearance) ▲ [α] ²⁵ _D ▼ + 14.1 ° (c0.9, chloroform: methanol 9: 1 (v / v)) NMR (CDCl ₃ −CD ₃ OD) δ (ppm) 0.90 (12H, t), 1.30 (s) 2.1 to 2.5 (8H, m), 5.1 to 5.3 (2H, m) Example 13 [Step 1] 2- (Diphenylphosphonoxy) ethyl 2
-Deoxy-6-0- [2-deoxy-4-0-diphenylphosphono-3-0-hexadecanoyl-6-0-
(2,2,2-trichloroethoxycarbonyl) -2- (2,
2,2-Trichloroethoxycarbonylamino) -β-D
-Glucopyranosyl] -3-0-hexadecanoyl-2
-Hexadecanoylamino-α-D-glucopyranoside 1-0-acetyl-2-deoxy-4-0-diphenylphosphono-3-0-hexadecanoyl-6-0- (2,
2,2-Trichloroethoxycarbonyl) -2- (2,2,2-
Trichloroethoxycarbonylamino) -D-glucopyranose is reacted with the compound obtained in Reference Example 9 in the same manner as in Step 1 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 15.6 ° (c1.0, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (9H, t), 2.0 to 2.4 (6H, m), 4.68, 4.75 (each) 2H, s), 5.05 (1H, t), 5.59 (1H, t), 7.2 to 7.5 (20H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 2
-Deoxy-6-0- [2-deoxy-4-0-diphenylphosphono-3-0-hexadecanoyl-2-hexadecanoylamino-β-D-glucopyranosyl) -3-
0-hexadecanoyl-2-hexadecanoylamino-
α-D-Glucopyranoside The compound obtained in Step 1 is reacted with palmitic acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a white powder.

▲ [α] ²⁵ _D ▼ + 5.8 ° (c1.0, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (12H, t), 2.0 to 2.4 (8H, m), 5.10 (1H, t) ), 5.49 (1H, t), 7.2 to 7.5 (20H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- (2-deoxy-3-0-hexadecanoyl-2
-Hexadecanoylamino-4-0-phosphono-β-D
-Glucopyranosyl) -3-0-hexadecanoyl-2
-Hexadecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 1 to obtain the title compound as a white powder.

Melting point 184-188 ° C (gradually browning, candy-like) ▲ [α] ²⁵ _D ▼ + 8.3 ° (c0.7, chloroform) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.89 (12H, t), 2.1 to 2.5 (8H, m), 5.1 to 5.4 (2H, m) Example 14 [Step 1] 2- (diphenyl) Phosphonoxy) ethyl 3
-0-[(R) -3-benzyloxytetradecanoyl] -2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0 -Diphenylphosphono-3-0-tetradecanoyl-6-0- (2,2,2-trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -β-D-glucopyranosyl} -Α-D-Glucopyranoside Compound H was used in the same manner as in Step 1 of Example 1 and Reference Example 2
React with the compound obtained in to give the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.90 (9H, t), 2.1 to 2.80 (6H, m), 4.54 (s), 5.08 (1H, t), 5.63 (1H, t), 7.2 to 7.5 ( 30H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 3
-0-[(R) -3-benzyloxytetradecanoyl] -2-[(R) -3-benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0 -Diphenylphosphono-3-0-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranosyl} -α-D-glucopyranoside The compound obtained in Step 1 was treated with tetradecane in the same manner as in Step 2 of Example 1. React with acid to give the title compound as a colorless oil.

NMR (CDCl ₃ ), δ (ppm): 0.90 (12H, t), 2.0 to 2.7 (8H, m), 4.48 (d), 4.52 (d), 5.14 (1H, t), 5.50 (1H, t) , 7.2 to 7.5 (30H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- (2-deoxy-4-0-phosphono-3-0-tetradecanoyl-2-0-tetradecanoylamino-β
-D-glucopyranosyl) -3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-hydroxytetradecanoylamino] -α-D-glucopyranoside Compound obtained in step 2 Is catalytically reduced in the same manner as in Step 3 of Example 6 to obtain the title compound as a white powder.

NMR (CDCl ₃ −CD ₃ OD), δ (ppm): 0.90 (12H, t), 1.26 (s), 2.1 to 2.5 (8H, m), 4.83 (1H, d), 5.1 to 5.4 (2H, m) ) Example 15 [Step 1] 2- (diphenylphosphonoxy) ethyl 2
-Deoxy-6-0- {2-deoxy-4-0-diphenylphosphono-6-0- (2,2,2-trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -3-0-[(R) -3- (2,2,2-trichloroethoxycarbonyloxy) tetradecanoyl-β-D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino- α-D-Glucopyranoside Compound G is reacted with the compound obtained in Reference Example 1 in the same manner as in Step 1 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 23.1 ° (c1.25, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (9H, t), 2.06 (2H, t), 2.3 to 2.6 (4H, m) ), 5.68 (1H, t), 7.2 to 7.5 (20H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 2
-Deoxy- {2-deoxy-4-0-diphenylphosphono-3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-hydroxytetradecanoylamino] -β -D-glucopyranosyl} -3-0-tetradecanoyl-2-tetradecanoylamino-α-D
-Glucopyranoside The compound obtained in Step 1 is reacted with (R) -3-hydroxytetradecanoic acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ ＋ 9.1 ° (c1.54, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (12H, t), 2.0 to 2.4 (8H, m), 5.10 (1H, t) ), 5.60 (1H, t), 7.2 to 7.5 (20H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- {2-deoxy-3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-hydroxytetradecanoylamino] -4-0-phosphono-β-
D-glucopyranosyl} -3-0-tetradecanoyl-
2-Tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 1 to give the title compound as a white powder.

Melting point 169-171 ° C (colored to become a candy) ▲ [α] ²⁵ _D ▼ + 6.2 ° (c1.22, chloroform: methanol = 3: 1, (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (12H, t), 1.26 (s), 2.1 to 2.6 (8H, m), 4.80 (d, 1H), 5.16 (1H, t), 5.34 (1H, t) Example 16 [Step 1] 2- (diphenylphosphonoxy) ethyl 3
-0-[(R) -3-benzyloxytetradecanoyl] -2-deoxy-6-0- [2-deoxy-4-0
-Diphenylphosphono-3-0-tetradecanoyl-6
-0- (2,2,2-trichloroethoxycarbonyl) -2
-(2,2,2-Trichloroethoxycarbonylamino)-
[beta] -D-Glucopyranosyl] -2-tetradecanoylamino- [alpha] -D-glucopyranoside Compound H was reacted with the compound obtained in Reference Example 10 in the same manner as in Step 1 of Example 1 to give the title compound as a colorless oil. Get as a thing.

NMR (CDCl ₃ ), δ (ppm): 0.89 (9H, t), 2.0 to 2.2 (4H, m), 2.4 to 2.7 (2H, m), 5.10 (1H, t), 5.62 (1H, t), 7.2-7.5 (25H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 3
-0-[(R) -3-benzyloxytetradecanoyl-2-deoxy-6-0- [2-deoxy-4-0-diphenylphosphono-2-[(R) -3-hydroxytetradecanoyl] Amino] -3-0-tetradecanoyl-β
-D-glucopyranosyl} -2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 was reacted with (R) -3-hydroxytetradecanoic acid in the same manner as in Step 2 of Example 1 to give the title compound. As a colorless oil.

▲ [α] ²⁵ _D ▼ + 6.6 ° (c1.18, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.89 (12H, t), 1.9 to 2.7 (8H, m), 4.83 (1H, d) ), 5.17 (1H, t), 5.53 (1H, t), 7.2 to 7.5 (25H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- {2-deoxy-2-[(R) -3-hydroxytetradecanoylamino] -4-0-phosphono-3-0
-Tetradecanoyl-β-D-glucopyranosyl} -3
-0-[(R) -3-hydroxytetradecanoyl-2
-Tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 6 to obtain the title compound as a white powder.

Melting point 148 to 151 ° C (colored to become a candy) ▲ [α] ²⁵ _D ▼ + 2.8 ° (c0.985, chloroform: methanol = 3: 1 (v / v)) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (12H, t), 1.26 (s), 2.10 to 2.50 (8H, m), 4.82 (1H, d), 5.1 to 5.3 (2H, m) Example 17 [Process 1 ] 2- (diphenylphosphonoxy) ethyl 2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-6-0- (2,2,2-trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -3-0-[(R) -3- (2,
2,2-Trichloroethoxycarbonyloxy) tetradecanoyl] -β-D-glucopyranosyl} -3-0-tetradecanoyl-α-D-glucopyranoside Compound G was prepared in the same manner as in Step 1 of Example 1 and Reference Example 11 React with the compound obtained in to give the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 24.1 ° (c1.24, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.88 (9H, t), 2.34 (4H, t) 2.4 to 2.7 (2H, m) , 4.50 (d) 5.70 (1H, t), 7.20 to 7.50 (25H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-3-0-[(R) -3-hydroxytetradecanoyl] -2-tetradecanoylamino-β-D-glucopyranosyl} -3-0-tetradecanoyl-α-D-glucopyranoside step The compound obtained in 1 is reacted with tetradecanoic acid in the same manner as in Step 2 of Example 1 to obtain the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 11.4 ° (c1.26, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (12H, t), 2.06 (2H, t) 2.2 to 2.4 (6H, m) , 4.50 (d) 5.06 (m), 5.56 (1H, t) 7.2 to 7.5 (25H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- {2-deoxy-3-0-[(R) -3-hydroxytetradecanoyl] -4-0-phosphono-2-tetradecanoylamino-β-D-glucopyranosyl} -2
-[(R) -3-Hydroxytetradecanoylamino]
-3-0-Tetradecanoyl-α-D-glucopyranoside The compound obtained in Step 2 is catalytically reduced in the same manner as in Step 3 of Example 6 to obtain the title compound as a white powder.

Melting point 166.5 to 168.5 ° C (gradual coloration to form a candy) ▲ [α] ²⁵ _D ▼ ＋ 8.9 ° (chloroform: methanol = 3:
1 (v / v)) NMR (CDCl ₃ −CD ₃ OD), δ (ppm): 0.90 (12H, t), 1.26 (s), 2.16 (2H, t), 2.32 (4H, m), 2.50 ( 2H, d), 4.82 (1H, d), 5.16 (1H, t), 5.32 (1H, t) Example 18 [Step 1] 2- (diphenylphosphonoxy) ethyl 2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-6-0- (2,2,2-trichloroethoxycarbonyl) -2- (2,2,2-trichloroethoxycarbonylamino) -3-0-[(R) -3- (2,
2,2-Trichloroethoxycarbonyloxy) tetradecanoyl] -β-D-glucopyranosyl} -3-0-
[(R) -3-Tetradecanoyloxytetradecanoyl] -α-D-glucopyranoside Compound G was reacted with the compound obtained in Reference Example 12 in the same manner as in Step 1 of Example 1 to give the title compound as a colorless compound. As an oil.

▲ [α] ²⁵ _D ▼ + 21.5 ° (c1.39, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (12H, t), 2.1 to 2.6 (8H, m) 4.52 (d), 5.72 (1H, t) 7.2 to 7.5 (25H, m) [Step 2] 2- (diphenylphosphonoxy) ethyl 2
-[(R) -3-Benzyloxytetradecanoylamino] -2-deoxy-6-0- {2-deoxy-4-0
-Diphenylphosphono-3-0-[(R) -3-hydroxytetradecanoyl] -2-[(R) -3-tetradecanoyloxytetradecanoylamino] -β-D-glucopyranosyl} -3- 0-[(R) -3-tetradecanoyloxytetradecanoyl] -α-D-glucopyranoside The compound obtained in Step 1 was treated with (R) -3-tetradecanoyloxy in the same manner as in Step 2 of Example 1. React with tetradecanoic acid to give the title compound as a colorless oil.

▲ [α] ²⁵ _D ▼ + 11.0 ° (c1.21, chloroform) NMR (CDCl ₃ ), δ (ppm): 0.90 (18H, t), 2.2 to 2.7 (12H, m), 4.50 ((d) 5.63 (1H, t) 7.2 to 7.5 (25H, m) [Step 3] 2-phosphonoxyethyl 2-deoxy-6
-0- {2-deoxy-3-0-[(R) -3-hydroxytetradecanoyl] -4-0-phosphono-2-
[(R) -3-Tetradecanoyloxytetradecanoylamino] -β-D-glucopyranosyl} -2-
[(R) -3-Hydroxytetradecanoylamino]-
3-0-[(R) -3-tetradecanoyloxytetradecanoyl] -α-D-glucopyranoside The compound obtained in Step 2 was catalytically reduced in the same manner as in Step 3 of Example 6 to give the title compound as a white powder. obtain.

Melting point 166.5 to 168.5 ° C (gradual coloration to form a candy) ▲ [α] ²⁵ _D ▼ ＋ 7.9 ° (c1.09, chloroform: methanol = 3: 1 (v / v) NMR (CDCl ₃ -CD ₃ OD), δ (ppm): 0.90 (18H, t), 1.26 (s) 2.2 to 2.7 (12H, m), 4.82 (d) 5.1 to 5.4 (m) Test Example BALB / c mice were treated with methylcholanthrene 2 × 10 ⁵ induced fibrosarcoma cells (MethA) were intradermally implanted into the flank of a syngeneic BALB / c mouse, and the triethylamine salt of the compound of the present invention was obtained on the 7th, 12th and 17th days after the implantation. Was dissolved or suspended in 0.1% triethylamine aqueous solution (v / v%) and adjusted to 500 μg / ml in the tail vein at 100 μg / mouse, and the effect of suppressing fibrosarcoma growth was observed 21 days later. It was judged.

Toxicity was determined by the number of dead mice / used mice 21 days after the above test.

 Table 1 shows the results.

Claims (1)

[Claims] 1. A general formula And a salt thereof, wherein Z represents an alkylene group having 1 to 9 carbon atoms. R represents a carboxyl group or a phosphonoxy group. R ¹ , R ² , R ³ and R ⁴ each independently represent a linear or branched acyl group having 2 to 60 carbon atoms, wherein the acyl group is a hydroxyl group or 2 to 30 carbon atoms.
It may have an acyloxy group. R ⁵ , R ⁶ and R ⁷ each independently represent a hydrogen atom or a phosphono group. ]