JPH0625273A - Aminosugar derivative - Google Patents

Abstract

PURPOSE:To provide a novel aminosugar drivative useful for treating multi- organ incompetences. CONSTITUTION:A compound of formula I {R<1> is substituent of formula II [Z<1>, Z<2> are 1-20C alkylene, phenylene; Z<11> is (phenyl-substituted)1-20C alkyl, (1-20C alkyl-substituted)phenyl, etc.], as for the substituent of the formula, CO-Z<3>-H, Z<3> is the same as Z<1>; R<2> is group of formula III (Z<4>, Z<5> are the same as Z<1>; Z<12> is the same as Z<11>), H, etc.; Q<1>, Q<2> are carboxyl, phosphonoxy; Q<3> is H, carboxy, etc.; Y<1> is 1-10C alkylene, but Y<1> may have a substituent of formula: OCOR<11> [R<11> is --Z<13> (the same as Z<11>), etc.], etc.; (m), (n) are 0-20} and its salt. For example 2-carboxy-1-(carboxymethyl)ethyl-6-0-[3-carboxy-2R,3R-bis) tetradecanoyloxy)propanoyl]-2-deoxy-3-0-(N-dodecanoylglycidyl)-2- tetradecanoylamino-alpha-D-glycopyranoiside. The compound of formula I is obtained by reducing a compound of formula IV in the presence of a catalyst such as palladium black under a hydrogen gas atmosphere in a solvent.

Description

Detailed Description of the Invention

[0001]

[Industrial applications]

[0002]

2. Description of the Related Art Acute lung injury and multiple organ failure are diseases with a very high mortality rate, and researches on their pathophysiology, early diagnosis and treatment are actively pursued. These onsets are often secondary or concurrent with infectious diseases, and in this case endotoxin is said to play a central role. Endotoxin is known to activate phagocytic cells such as macrophages, and it is considered that various cytokines induced by activation are involved in pathological conditions.

Cytokines that are deeply involved in lung damage and multiple organ failure include tumor necrosis substances (TNF) and interleukins, which have been confirmed to cause acute lung damage in animal experimental systems.

[0004] At present, studies on monoclonal antibodies against endotoxin or TNF have been conducted as potential preventive and therapeutic agents, and their effectiveness has been confirmed in animal experimental model systems. However, a sufficient treatment method has not been established clinically.

The present inventor has tried to find a compound which is expected to have a superior therapeutic effect which is clinically applicable.
It was found that the compound represented by the formula I serves the purpose of suppressing the induction of TNF of human macrophages by endotoxin, and completed the present invention.

[0006]

The present invention is of general formula I

[0007]

[Chemical 2]

The present invention relates to a compound represented by and a salt thereof.
The symbols in the formula have the following definitions. R ¹ is a substituent group -CO-Z ¹ -N (Z
¹¹ ) -CO-Z ² -H or the substituent -CO-Z ³ -H. Representative examples include tetradecanoyl, dodecanoyl, decanoyl, N-dodecanoylglycyl, N-dodecanoyl sarcosyl, 6-octanoylaminohexanoyl, 8-hexanoylaminooctanoyl, 6-benzoylaminohexa Mention may be made of noyl, 8-benzoylaminooctanoyl, p-octanoylaminobenzoyl, 8-phenyloctanoyl, p-octylbenzoyl, N-dodecanoyl-N-dodecylglycyl. Total carbon number of Z ¹ and Z ² is 10-16
And the acyl group in which Z ³ has 9 to 15 carbon atoms are preferable examples.

R ² represents a substituent —CO—Z ⁴ —N (Z ¹² ) —CO—Z ⁵ —H, a substituent —CO—Z ⁶ —H or a hydrogen atom. As typical examples other than hydrogen atom, tetradecanoyl, dodecanoyl, decanoyl, N-dodecanoylglycyl, N-dodecanoylsarcosyl, 6-octanoylaminohexanoyl,
8-hexanoylaminooctanoyl, 6-benzoylaminohexanoyl, 8-benzoylaminooctanoyl, p-
Mention may be made of octanoylaminobenzoyl, 8-phenyloctanoyl, p-octylbenzoyl, N-dodecanoyl-N-dodecylglycyl.

Q ¹ means a carboxyl group or a phosphonoxy group. Q ² means a carboxyl group or a phosphonoxy group. Q ³ represents a hydrogen atom, a carboxyl group or a phosphonoxy group. m means an integer of 0 to 20. n means an integer of 0 to 20. Y ¹ has ¹ to 10 carbon atoms
10 alkylene groups, which may have one or more substituents —0COR ¹¹ and / or substituents —NHCOR ¹² . Ethylene or propylene is a preferred example as the alkylene. R ¹¹ is a substituent -Z ¹³ or a substituent
-Z ⁷ -N (Z ¹⁴ ) -CO-Z ⁸ -H means. A group in which the total number of carbon atoms of Z ⁷ and Z ⁸ is 9 to 15 is a preferable example. R ¹² means the substituent —Z ¹⁵ or the substituent —Z ⁹ —N (Z ¹⁶ ) —CO—Z ¹⁰ —H. Z ⁹ and Z ¹⁰
A group having a total carbon number of 9 to 15 is a preferable example.

Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ , Z ⁶ , Z ⁷ , Z ⁸ , Z ⁹ and Z ¹⁰ are each a combination of an alkylene group having 1 to 20 carbon atoms and a phenylene group or a combination thereof. Means one. For example, phenylene (-C ₆ H ₄ -), methylene (-CH ₂ -), ethylene (-CH ₂ CH ₂ -),
Tetramethylene _{(- (CH 2) 4 -} ), pentamethylene (- (CH _2)
5- ), hexamethylene (-(CH ₂ ) _6- ), heptamethylene (-(CH
_{2) 7} -), nonamethylene (- (CH _{2) 9} -), undecamethylene (-
(CH _{2) 11} -), dodecamethylene _{(- (CH 2) 12 -} ), tridecamethylene _{(- (CH 2) 13 -} ), or formula _{-CH 2 C 6 H 4 -,} - (CH 2) 7 C ₆ H ₄ -,
A group represented by —CH ₂ C ₆ H ₄ CH ₂ — may be mentioned.

Z ¹¹ , Z ¹² , Z ¹³ , Z ¹⁴ , Z ¹⁵ and Z ¹⁶ each have a carbon number of 1 to 1 which may be substituted by a phenyl group.
20 alkyl groups, for example methyl, ethyl, pentyl,
Heptyl, nonyl, undecyl, dodecyl, tridecyl, benzyl, 3-phenylpropyl, 5-phenylpentyl, 7-phenylheptyl, phenyl group which may be substituted by an alkyl group having 1 to 20 carbon atoms, for example, p-hexylphenyl , P-octylphenyl, p-decylphenyl,
An alkylene group having 1 to 20 carbon atoms which may include a phenylene group, for example, 7- (p-toluyl) heptyl, 3-
(p-Butylphenyl) propyl or a hydrogen atom.

Representative examples of the substituent-0COR ¹¹ include decanoyloxy, dodecanoyloxy, tetradecanoyloxy, 8-phenyloctanoyloxy, 6-benzoylaminohexanoyloxy, N-dodecanoylglycyloxy, N-dodecanoyl sarcosyloxy, 6-octanoylaminohexanoyloxy, 8-hexanoylaminooctanoyloxy, 6-benzoylaminohexanoyloxy, 8-benzoylaminooctanoyloxy, p-octanoylaminobenzoyloxy, Mention may be made of 8-phenyloctanoyloxy, p-octylbenzoyloxy, N-dodecanoyl-N-dodecylglycyloxy.

As typical examples of the substituent —NHCOR ¹² , dodecanoylamino, tetradecanoylamino, N-dodecanoylglycylamino, N-dodecanoylsarcosylamino,
6-octanoylaminohexanoylamino, 8-hexanoylaminooctanoylamino, 6-benzoylaminohexanoylamino, 8-benzoylaminooctanoylamino, p-octanoylaminobenzoylamino, 8-phenyloctanoylamino, p -Octylbenzoylamino, N-dodecanoyl-N-dodecylglycyl dodecanoylamino may be mentioned.

When a plurality of substituents -0COR ¹¹ and / or substituents -NHCOR ¹² are present in one compound, a plurality of moieties represented by R ¹¹ or R ¹² do not necessarily represent the same thing, but different groups. It may be a combination. For example, tetradecane and dodecane, tetradecane and dodecanoylaminomethyl, tetradecane and dodecane and decane, or two tetradecane and one dodecane may be freely combined.

The compound of the present invention is a salt with an organic amine such as triethylamine, pyridine, N-methylglucamine, tris (hydroxymethyl) aminomethane or a salt with an inorganic base such as ammonium, sodium, potassium, calcium or magnesium. Can also be

The compounds of the present invention will be illustrated below with more specific substituents and combinations thereof. In the present specification, examples of the substituents and the like may be expressed by using the following abbreviations and the like in the present specification, and even if not specifically exemplified here, various groups are represented by the same method. It can also be expressed.

The illustrated tetradecanoyl representation _{substituents: -CO (CH 2) 12 CH} 3: -C14 N- dodecanoyl _{glycyl: -COCH 2 NHCOCH (CH 2)} 10 CH 3: -GlyC12 4- carboxy - 2- (tetradecanoyl amino) _{butanoyl: -COCH (NHCO (CH 2)} 12 CH 3) CH 2 CH 2 COOH: -COCH (NHC14) CH 2 CH 2 COOH 3- phosphonoxy 2-tetradecanoylaminophenoxy: - _{COCH (NHCO (CH 2) 12} CH 3) CH 2 OPO (OH) 2: -COCH (NHC14) CH 2 OPO (OH) 2 8- benzoylamino _{octanoyl: -CO (CH 2) 7 NHCOC} 6 H 5: -C8NBz _{p-octanoyl-aminobenzoyl: -COC 6 H 4 NHCO (CH} 2) 6 CH 3: -BzNC8 6- octanoylamino _{hexanoyl: -CO (CH 2) 5 NHCO} (CH 2) 6 CH 3: - C6NC8 6-Benzoylaminohexanoyl: -CO (CH ₂ ) ₅ NHCOC ₆ H ₅ : -C6NBz N-Dodecanoyl sarcosyl: -COCH ₂ N (CH ₃ ) CO (CH ₂ ) ₁₀ CH ₃ : -SarC12

[0019]Examples of substituents -CO-Y¹-Q¹Example: -COCH₂CH₂CH (NHC14) COOH -COCH₂CH (OC14) COOH -COCH₂CH (OC8NBz) COOH -COCH (OC8NBz) CH (OC8NBz) COOH -COCH₂CH (NHC8NBz) CH₂COOH -COCH (NHSarC12) CH₂CH₂COOH -COCH (NHC14) CH₂CH₂COOH -COCH (NHC14) CH₂COOH -COCH (NHC6NBz) CH₂CH₂COOH -COCH (NHC8C ₆H _Five) CH₂CH₂COOH -COCH (NHBzNC8) CH₂CH₂COOH -COCH (NHC8NBz) CH₂COOH -COCH (NHC8NBz) CH₂CH₂COOH -COCH (NHC8NBz) CH (OGlyC12) COOH -COCH (NHC14) CH (OC14) COOH R¹And R²Example: -C14 -C12 -GlyC12 -BzNC8 -C6NC8 -SarC12 -C6NBz Q²And Q³Example: -OPO (OH)₂ -COOH HExamples of combinations of substituents on specific compounds:

[0020]

[Table 1]

[0021]

[Table 2]

The compound of the present invention can be produced by the method exemplified by the following reaction scheme.

[0023]

[Chemical 3] (In the formula, Q ¹⁰ represents a carboxyl group having a protecting group or a phosphonoxy group having a protecting group. Q ²⁰ represents a carboxyl group having a protecting group or a phosphonoxy group having a protecting group. Q ³⁰ represents a protecting group. Means a carboxyl group having a protective group, a phosphonoxy group having a protective group or a hydrogen atom, R ²⁰ is a protective group for a hydroxyl group, a substituent group -CO-Z ⁴ -N (Z ¹² )-
CO-Z ⁵ -H or the substituent -CO-Z ⁶ -H is meant. Y ¹ , Z ⁴ ,
Z ⁵ , Z ⁶ and Z ¹² are the same as above. ) The protecting groups in the 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 phosphonoxy 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.

As the protective group for the hydroxyl group, a halogen atom,
Examples thereof include a benzyl group and a benzyloxycarbonyl group which may have a substituent such as a nitro group and a lower alkoxy group, and a trichloroethoxycarbonyl group.

In order to form the compound of the formula I, the protecting group of the carboxyl group and / or the protecting group of the phosphonoxy group of the compound of the formula II, and further the protecting group of the hydroxyl group which may be present may be eliminated. In this reaction, compound II is subjected to catalytic reduction by treatment with tetrahydrofuran, methanol, ethanol, acetic acid, water or the like alone or in a mixed solvent under a hydrogen gas atmosphere using palladium black, palladium carbon or a platinum dioxide catalyst. Appropriate.

When compound II has a trichloroethoxycarbonyl group as a hydroxyl protecting group and this and other types of protecting groups coexist, the trichloroethoxycarbonyl group is first treated with zinc dust in acetic acid to be eliminated. It is common to then remove the other protecting group.

The produced target compound can be obtained by purifying it by silica gel column chromatography or the like, if necessary, and then appropriately desalting it by an electrodialysis method, an acid precipitation method, an ion exchange resin method or the like.

The compound of the present invention can also be obtained in the form of a salt by adding a necessary amount of a base and performing an appropriate method such as a precipitation method or a freeze-drying method. In addition, the compounds of the present invention have α-configuration and β-configuration with respect to the steric configuration at the 1-position of the sugar, but the α-configuration often exhibits more excellent effects.

The compound of formula II used as a starting material can be prepared as follows. A route

[0031]

[Chemical 4] The compound of formula II can be produced by condensing the 6-position primary hydroxyl group of the compound of formula 1 and the carboxyl group of the compound of formula 2 using an ester condensation reaction such as an acid chloride method or a carbodiimide method. In the carbodiimide method, in addition to a condensing agent such as dicyclohexylcarbodiimide, a catalyst such as 4-dimethylaminopyridine is added, or a reagent that produces an active ester such as 1-hydroxybenzotriazole is added to allow the reaction to proceed smoothly. You can Route B In addition to the above-mentioned route A, the following route is available for producing the compound II in which the substituent Y ¹ has a portion represented by —NHCOR ¹² .

[0032]

[Chemical 5]

(In the formula, Y ¹⁰ represents an alkylene group having at least one amino group having a protecting group, and may further have one or more substituents —0COR ¹¹ and / or substituents —NHCOR ^12. there .Y ²⁰ is the amino group having a protecting group of Y ^10, except that the protecting group is eliminated is the same as defined Y ¹⁰ .R ¹¹ and R ¹² is the same.) in other words, protected on the Compound II obtained by condensing Compound 2a having an amino group to Compound 1 in the same manner as A route
The a-protecting group of the amino group is eliminated by treating a with trifluoroacetic acid or zinc powder in acetic acid, and the resulting compound IIb is converted to a carboxylic acid represented by the formula R ¹² COOH by an acid chloride method or a carbodiimide. Law, Eintopf
Substituent-NHC
Compound II with OR ¹² is produced.

Examples of the amino group-protecting group include tertiary butoxycarbonyl group, trichloroethoxycarbonyl group and methoxybenzyloxycarbonyl group, which are commonly used in this field.

The starting compound of formula 1 can be prepared by a method described in the literature (eg, T. Kusama et.al, Chem. Pharm. Bull., 38, 3366 (199).
0), T.Kusama et.al, Chem.Pharm.Bull., 39,3244 (199
1)) or a method according to it.

The raw material compound of formula 2 or compound 2a can be easily synthesized from a carboxylic acid derivative having an amino group and / or a hydroxyl group and / or a carboxyl group such as tartaric acid, glutamic acid and serine. For example,
For the amino group, tertiary butoxycarbonyl group or 2,2,2-
It can be synthesized by introducing a protecting group such as a trichloroethoxycarbonyl group or an acyl group represented by the formula R ¹² CO-.

The hydroxyl group can be synthesized by introducing an acyl group represented by the formula R ¹¹ CO- or a protected phosphonoxy group.

Further, in a compound having two carboxyl groups, a protecting group such as a benzyl group can be introduced into one of the compounds to obtain a desired raw material.

Although some of these compounds are commercially available,
The synthetic method was also illustrated in the reference example.

[0040]

【Example】

Example 1 2-Carboxy-1- (carboxymethyl) ethyl
6-O- [3-Carboxy-2R, 3R-bis (tetradecanoyloxy) propanoyl] -2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D -Production of glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [3-benzyloxycarbonyl-
2R, 3R-Bis (tetradecanoyloxy) propanoyl]-
2-Deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 252 mg 30
It was dissolved in ml of tetrahydrofuran, 50 mg of 10% palladium-carbon was suspended, and the mixture was vigorously stirred at room temperature under a hydrogen stream for 3 hours. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was subjected to thin layer chromatography (chloroform: methanol:
Water = 6: 4: 0.15 (v / v)) and treated with strong acid ion exchange resin Dowex 50W-X2 (H ⁺ type, Dow Chemical Co.). The solvent was distilled off under reduced pressure and the obtained residue was dissolved in dioxane and freeze-dried to obtain 108 mg of the title compound as a white powder. Unclear melting point

[Α] _D ^{twenty five} + 21.6 ° (c 0.5, chloroform
Mu: Methanol = 3: 1 (v / v)) IR (KBr) ν max (cm^-1) ； 3400,1750,1645,1545,1470,
1205.¹ H-NMR (CDCl₃-CD₃OD (1: 1) / TMS): δ = 0.89 (12H, t, J = 7H
z), 1.28 (76H, s), 1.5-1.7 (8H, m), 2.2-2.3 (4H, m), 2.4
-2.5 (4H, m), 2.68 (3H, m), 2.80 (1H, dd, J = 16Hz, 6Hz), 3.
90 and 3.96 (each 1H, AB type d, J = 18Hz), 3.97 (1H,
m), 4.17 (1H, dd, J = 11Hz, 3Hz), 4.35-4.5 (3H, m), 4.95 (1
H, d, J = 3Hz), 5.06 (1H, t, J = 10Hz), 5.78 (2H, br).

Example 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [4-carboxy-2R- (tetradecanoylamino) butanoyl] -2-deoxy-3-O- (N-dodecanoyl) Glycyl) -2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (Tetradecanoylamino) butanoyl] -2-deoxy
-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 293 mg was dissolved in 30 ml of tetrahydrofuran, 80 mg of 10% palladium-carbon was added, and the mixture was stirred under hydrogen flow at room temperature. Vigorously stirred for 2 hours. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was subjected to thin layer chromatography (chloroform: methanol: water = 6: 4: 0.6).
(developed at (v / v)) and treated with strong acid ion exchange resin Dowex 50W-X2 (H ⁺ type, manufactured by Dow Chemical Co.). The solvent was distilled off under reduced pressure and the obtained residue was dissolved in dioxane and freeze-dried to obtain 177 mg of the title compound as a white powder. Melting point is unclear, and it begins to become candy-like at 125-130 ℃.

[Α] _D ^{twenty five} +30.3 ° (c 0.5, chloroform
Mu: Methanol = 3: 1 (v / v)) IR (KBr) ν max (cm^-1); 3350,1730,1650,1545,1210.¹ H-NMR (CDCl₃-CD₃OD (1: 1) / TMS): δ = 0.89 (9H, t, J = 7H
z), 1.27 (56H, s), 1.55-1.7 (6H, m), 2.01 (1H, m), 2.15-
2.3 (7H, m), 2.44 (2H, t, J = 7Hz), 2.67 (3H, m), 2.80 (1H, d
d, J = 16Hz, 7Hz), 3.65 (1H, t, J = 10Hz), 3.90 and 3.97 (ea
ch 1H, AB type d, J = 18Hz), 4.00 (1H, m), 4.16 (1H, dd, J
= 11Hz, 3Hz), 4.35 (1H, dd, J = 12Hz, 5Hz), 4.44 (2H, m), 4.
52 (1H, dd, J = 8Hz, 6Hz), 4.99 (1H, d, J = 4Hz), 5.07 (1H, t, J
= 10Hz).

Example 3 2-Carboxy-1- (carboxymethyl) ethyl 2-deoxy-3-O- (N-dodecanoylglycyl) -6-O- [3-phosphonoxy-2R- (tetradecanoylamino) ) Propyl] -2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-6-O- [3-diphenylphosphonoxy-2R -(Tetradecanoylamino) propanoyl]
-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 259 mg was dissolved in 30 ml of tetrahydrofuran, 70 mg of 10% palladium carbon was added, and the mixture was stirred under hydrogen atmosphere at room temperature. Vigorously stirred for 2 hours. Subsequently, 140 mg of platinum dioxide was added to the reaction solution, and the mixture was vigorously stirred under a hydrogen stream at room temperature for 24 hours. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by thin layer chromatography (developing solvent; chloroform: methanol: water = 6: 4: 0.8) and strongly acidic ion exchange resin Dowex 50W-X2 (H ⁺
Mold, manufactured by Dow Chemical Co., Ltd.). The solvent was distilled off under reduced pressure and the obtained residue was dissolved in dioxane and freeze-dried to obtain 117 mg of the title compound as a white powder. Melting point unclear, 1
Colors brown at around 45 ° C.

[Α] _D ^{twenty five} +27.1 ° (c 0.5, chloroform
Mu: Methanol = 3: 1 (v / v)) IR (KBr) ν max (cm^-1); 3350, 1745, 1720, 1645, 155
0, 1210, 1030.¹ H-NMR (CDCl₃-CD₃OD (1: 1) / TMS): δ = 0.89 (9H, t, J = 7H
z), 1.27 (56H, s ~ m), 1.5-1.7 (6H, m), 2.2-2.3 (6H, m),
2.67 (3H, m), 2.80 (1H, dd, J = 16Hz, 7Hz), 3.62 (1H, t, J = 10
Hz), 3.90 (1H, AB type d, J = 18Hz), 3.95 (1H, AB type d,
J = 18Hz), 4.01 (1H, m), 4.15 (1H, dd, J = 11Hz, 4Hz), 4.23
(1H, m), 4.4-4.5 (4H, m), 4.80 (1H, m), 5.00 (1H, d, J = 4H
z), 5.07 (1H, t, J = 10Hz).

Reference Example 1 2-Benzyloxycarbonyl-1
-(Benzyloxycarbonylmethyl) ethyl 6-O- [3-
Benzyloxycarbonyl-2R, 3R-bis (tetradecanoyloxy) propanoyl] -2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 308 mg 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 5 ml of dried chloride Dissolve in methylene and add 238 mg of 2,3-bis-O-tetradecanoyl-L-
Tartaric acid monobenzyl ester and 4 mg of 4-dimethylaminopyridine were added. Once ice-cooled, 81 mg of dicyclohexylcarbodiimide and 50 mg of 1-hydroxybenzotriazole were added, and the mixture was stirred at room temperature for 3 hours. 1 in the reaction solution
After adding ml of methanol and stirring, the mixture was diluted with chloroform, and this was washed successively with 1N hydrochloric acid, 5% aqueous sodium hydrogen carbonate solution and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to a silica gel column (elution solvent; chloroform containing 5% acetone,
(Change to chloroform containing 1% methanol from the middle)
The title compound (294 mg) was obtained as a colorless oil by purification.

[Α] _D ^{twenty five} + 26.2 ° (c 1.4, chloroform
)¹ H-NMR (CDCl₃/ TMS): δ = 0.88 (12H, t, J = 6Hz), 1.25 (76
H, m), 1.5-1.7 (8H, m), 2.1-2.4 (8H, m), 2.60 (1H, dd, J = 1
6Hz, 7Hz), 2.68 (2H, m), 2.84 (1H, dd, J = 16Hz, 6Hz), 3.55
(1H, t, J = 10Hz), 3.85 (1H, dd, J = 18Hz, 5Hz), 3.88 (1H, m),
 4.10 (1H, dd, J = 17Hz, 6Hz), 4.20 (1H, td, J = 10Hz, 4Hz),
4.4 (3H, m), 4.88 (1H, d, J = 4Hz), 5.00 (1H, t, J = 10Hz), 5.
05-5.25 (6H, m), 5.73 and 5.80 (each 1H, d, J = 3Hz), 6.4
0 (1H, t, J = 5Hz), 6.61 (1H, d, J = 9Hz), 7.33 (15H, m).

Reference Example 2 2-Benzyloxycarbonyl-1
-(Benzyloxycarbonylmethyl) ethyl 6-O- [4-
Benzyloxycarbonyl-2R- (tetradecanoylamino) butanoyl] -2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 380 mg 2-benzyl Oxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside was dissolved in 6 ml of dry methylene chloride. , 143 mg N-tert-butoxycarbonyl-D-glutamic acid γ-benzyl ester and 5 mg 4-dimethylaminopyridine were added. After cooling with ice, 100 mg of dicyclohexylcarbodiimide was added, and the mixture was stirred at the same temperature for 45 minutes. After adding 1 ml of methanol to the reaction solution and stirring, the solvent was distilled off under reduced pressure. The obtained residue was purified by a silica gel column (elution solvent; chloroform containing 5% acetone, changed from halfway to chloroform containing 2% methanol).
Yield mg yellow oil.

320 mg of this oily substance was dissolved in 4 ml of dry methylene chloride, 4 ml of trifluoroacetic acid was added under ice cooling, and the mixture was stirred at the same temperature for 1 hour. The solvent was distilled off under reduced pressure, and the procedure of adding toluene to the residue and distilling off under reduced pressure was repeated to obtain an oily substance. Meanwhile, 86 mg of myristic acid and 61 mg of 1-hydroxybenzotriazole in 3 ml
Dissolve it in dry tetrahydrofuran at
g of dicyclohexylcarbodiimide was added, the mixture was returned to room temperature and stirred for 2 hours, and the precipitated crystals were removed by filtration. The filtrate and the solution obtained by dissolving the above oily substance in 6 ml of dry methylene chloride were mixed under ice-cooling, subsequently 52 μl of triethylamine was added, and the mixture was returned to room temperature and stirred for 17 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column (change to chloroform containing 5% acetone, then chloroform containing 1% methanol, and chloroform containing 3% methanol) to give 309 mg of the title compound. Was obtained as a waxy solid.

[Α] _D ^{twenty five} +24.5 ° (c 1.0, chloroform
)¹ H-NMR (CDCl₃/ TMS): δ = 0.88 (9H, t, J = 7Hz), 1.24 (56H,
m), 1.55-1.7 (6H, m), 2.02 (1H, m), 2.1-2.5 (9H, m), 2.5
9 (1H, dd, J = 17Hz, 7Hz), 2.67 (2H, m), 2.87 (1H, dd, J = 16H
z, 6Hz), 3.63 (1H, t, J = 10Hz), 3.86 (1H, d ~ br), 3.93 (1H,
m), 4.12 (1H, d ~ br), 4.22 (1H, m), 4.30 (1H, dd, J = 12Hz, 2
Hz), 4.40 (2H, m), 4.56 (1H, m), 4.89 (1H, d, J = 4Hz), 5.0
4 (1H, t, J = 10Hz), 5.12 (6H, m), 6.36 (1H, d, J = 7Hz), 6.42
(1H, br), 6.63 (1H, d, J = 9Hz), 7.34 (15H, m).

Reference Example 3 2-Benzyloxycarbonyl-1
-(Benzyloxycarbonylmethyl) ethyl 2-deoxy-6-O- [3-diphenylphosphonoxy-2R- (tetradecanoylamino) propanoyl] -3-O- (N-dodecanoylglycyl) -2- Tetradecanoylamino-α-D-glucopyranoside 436 mg 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoyl Amino-α-D-glucopyranoside was dissolved in 8 ml of dry methylene chloride and 203 mg of N-tert-butoxycarbonyl-O-diphenylphosphono-D-serine and 6 mg of 4-dimethylaminopyridine were added. The mixture was ice-cooled, 115 mg of dicyclohexylcarbodiimide was added, and the mixture was stirred at the same temperature for 30 minutes. After adding 1 ml of methanol to the reaction solution and stirring, the solvent was distilled off under reduced pressure. Acetonitrile was added to the residue, the insoluble was filtered off, the solvent was distilled off under reduced pressure again, and the resulting residue was purified by a silica gel column (elution solvent; chloroform containing 1% methanol) to give a yellow viscous liquid. A thick oil was obtained. 496 mg of this oil was dissolved in 5 ml of dry methylene chloride,
Under ice cooling, 3 ml of trifluoroacetic acid was added, and the mixture was stirred at the same temperature for 1 hour. The solvent was distilled off under reduced pressure, and the procedure of adding toluene to the residue and distilling off under reduced pressure was repeated to obtain an oily substance.

On the other hand, 124 mg of myristic acid and 88 mg of 1-
Hydroxybenzotriazole was dissolved in 3 ml of dry tetrahydrofuran, 119 mg of dicyclohexylcarbodiimide was added under ice cooling, the mixture was returned to room temperature and stirred for 2 hours, and the precipitated crystals were removed by filtration. This filtrate and 6 ml of a dry methylene chloride solution of the above oily substance were mixed under ice cooling, 75 μl of triethylamine was added, and the mixture was returned to room temperature.
Stir for 18 hours. The solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column (eluent: chloroform containing 5% acetone, changing from halfway to chloroform containing 1.5 methanol) to give 288 mg of the title compound as a pale yellow oil. I got it as a thing.

[Α] _D ^{twenty five} +20.4 ° (c 1.0, chloroform
)¹ H-NMR (CDCl₃/ TMS): δ = 0.88 (9H, m), 1.24 (56H, m), 1.
5-1.7 (6H, m), 2.1-2.3 (6H, m), 2.52-2.72 (3H, m), 2.86
(1H, dd, J = 16Hz, 6Hz), 3.54 (1H, t, J = 10Hz), 3.83 (1H, dd,
J = 18Hz, 5Hz), 3.93 (1H, m), 4.10 (1H, dd, J = 18Hz, 6Hz),
4.19 (1H, m), 4.26 (1H, dd, J = 12Hz, 2Hz), 4.35-4.5 (3H,
m), 4.64 (1H, m), 4.85 (2H, d, J = 4Hz and m), 5.02 (1H, t, J
= 10Hz), 5.12 (4H, m), 6.47 (1H, br), 6.58 (1H, d, J = 7Hz),
6.65 (1H, d, J = 9Hz), 7.1-7.4 (20H, m).

Reference Example 4 2,3-bis-O-tetradecanoyl-
L-tartaric acid monobenzyl ester 1.48 g of L-tartaric acid monobenzyl ester was dissolved in 20 ml of ethyl acetate, and 1.35 g of phenyl bromide and 0.
94 ml of triethylamine was added, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was washed successively with water, 1N hydrochloric acid, 5% aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue is a silica gel column (eluting solvent; chloroform: acetone =
19: 1 and changed from 9: 1 to 9: 1) to obtain 2.10 g of L-tartaric acid benzylphenacyl ester as a pale yellow oil.

[Α] _D ^{twenty five} + 1.3 ° (c 1.2, chloroform)¹ H-NMR (CDCl₃/ TMS): δ = 3.0 (2H, br), 4.81 (2H, m), 5.
30 (2H, s), 5.49 (2H, s), 7.2-8.0 (10H, m). 2.01 g of this compound was dissolved in 30 ml of dry methylene chloride.
Scarecrow, 3.33 g of tetradecanoic acid chloride under ice cooling, 1.09 m
l pyridine and 0.14 g 4-dimethylaminopyridine
Was added, and the mixture was stirred at the same temperature for 1 hour. Add 1 part of the reaction solution to water.
Wash successively with constant hydrochloric acid and saturated saline, anhydrous sodium sulfate
After drying in, the solvent was distilled off under reduced pressure. The residue is silica gel
Rum (elution solvent; hexane: ethyl acetate = 9: 1, halfway
Changed to 4: 1) and 2,3-bis-O-tetradecanoic acid
Le-L-tartaric acid benzylphenacyl ester wax
3.81 g of a white solid was obtained. Melting point: 51-52 ℃

[Α] _D ^{twenty five} + 12.0 ° (c 2.5, chloroform
M) IR (KBr) ν max (cm^-1); 1770, 1750, 1705, 1210, 11
50.¹ H-NMR (CDCl₃/ TMS): δ = 0.88 (6H, s-t), 1.25 (40H, s),
2.1-2.7 (4H, m), 5.19 (1H, AB type d, J = 16Hz), 5.21 (2
H, s-ABq), 5.57 (1H, AB type d, J = 16Hz), 5.87 (1H, d, J = 3
Hz), 5.93 (1H, d, J = 3Hz), 7.3-7.9 (10H, m). Dissolve 3.404 g of this compound in 40 ml of acetic acid to obtain 2.0 g of
Zinc powder was added and vigorously stirred at room temperature. 2 hours later 50 ° C
For 3 hours, adding 1 g of zinc powder 3 times
It was stirred. Insoluble matter is filtered off and washed with chloroform.
The filtrate was evaporated under reduced pressure. Toluene was added to the obtained residue.
After repeating the procedure of distilling off the solvent under reduced pressure, the residue is
It was diluted with loroform and washed with 1N hydrochloric acid. Anhydrous sulfuric acid
After drying over sodium, the solvent was distilled off under reduced pressure, and the obtained residue
Silica gel column (elution solvent; 2% methanol
Purify with chloroform containing, change from 10% to 10%),
2,3-Bis-O-tetradecanoyl-L-tartrate monobenzyl
2.88 g of ester was obtained as a colorless oil.

[Α] _D ^{twenty five} + 9.8 ° (c 1.9, chloroform)¹ H-NMR (CDCl₃/ TMS): δ = 0.88 (6H, t, J = 7Hz), 1.25 (40H,
s), 1.4-1.6 (4H, m), 2.1-2.4 (4H, m), 5.07 (1H, AB type
 d, J = 12Hz), 5.18 (1H, AB type d, J = 13Hz), 5.59 (1H, br),
 5.92 (1H, br), 7.27 (5H, m).

Reference Example 5 N-tertiary butoxycarbonyl-O-
Diphenylphosphono-D-serine 3.75 g of N-tertiary butoxycarbonyl-D-serine benzyl
Dissolve the ester in 30 ml of dry methylene chloride at room temperature
At 1.23 ml pyridine, 1.86 g 4-dimethylaminopyr
Gin, followed by 4.09 g of diphenylphosphorochloridate
In addition, the mixture was stirred at the same temperature for 3 hours. 1 reaction mixture
Wash with constant hydrochloric acid and saturated saline, and wash the organic layer with anhydrous sodium sulfate.
After drying over triumnium, the solvent was distilled off under reduced pressure. Residue obtained
Silica gel column (elution solvent; contains 2% acetone)
Chloroform), N-tert-butoxycarbonyl
-O-diphenylphosphono-D-serine benzyl ester 5.
38 g was obtained as a white solid. Melting point: 108-109 ℃ [α] _D ^{twenty five} -14.8 ° (c 1.2, chloroform) IR (KBr) ν m
ax (cm^-1): 3300,1750,1710,1590,1530,1490.¹ H-NMR (CDCl₃/ TMS): δ = 1.42 (9H, s), 4.5-4.7 (3H, m),
 5.07 (1H, AB type d, J = 12Hz), 5.16 (1H, AB type d, J = 12
Hz), 5.39 (1H, d, J = 8Hz), 7.1-7.4 (15H, m).

5.19 g of this compound was added to 40 ml of tetrahydride
Dissolve in lofran and add 200 mg of 10% palladium on carbon.
Then, the mixture was vigorously stirred under a hydrogen stream at room temperature for 2 hours. Filter the catalyst
The solvent of the filtrate was distilled off under reduced pressure. Residue in ethyl acetate
It was dissolved and extracted with a 5% aqueous sodium hydrogen carbonate solution. water
The layer was adjusted to pH 2-3 with an aqueous citric acid solution and washed with ethyl acetate.
It was extracted and washed with saturated saline. The organic layer is
After drying with thorium, the solvent was distilled off under reduced pressure to give the title compound.
4.11 g was obtained as a colorless oil. [Α] _D ^{twenty five} -32.3 ° (c 1.2, chloroform)¹ H-NMR (CDCl₃/ TMS): δ = 1.42 (9H, s), 4.56 (2H, m), 4.6
7 (1H, m), 5.54 (1H, d, J = 7Hz), 7.15-7.4 (10H, m).

Example 4 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [2R- (8-benzoylaminooctanoylamino) -4-benzoyloxycarbonylbutanoyl] -2 -Deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxy) was prepared in the same manner as in Step 1 of Example 2. Carbonylmethyl) ethyl
2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside obtained by condensing N-tertiary butoxycarbonyl-D-glutamic acid γ-benzyl ester 374 mg of 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl
6-O- [4-benzoyloxycarbonyl-2R- (tert-butoxycarbonylamino) butanoyl] -2-deoxy-3-O- (N-
Dodecanoylglycyl) -2-tetradecanoylamino-α-
D-Glucopyranoside was reacted with 117 mg of 8-benzoylaminooctanoic acid to give 312 mg of the title compound as a white waxy solid.

[Α] _D + 25.8 ° (c 1.1, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.87 (6H, t, J = 7Hz), 1.24 (44H,
m), 1.60 (8H, m), 2.01 (1H, m), 2.16 (5H, m), 2.24 (2H, t,
J = 7Hz), 2.44 (2H, m), 2.59 (1H, dd, J = 16Hz, 7Hz), 2.66 (2
H, m), 2.84 (1H, dd, J = 16Hz, 6Hz), 3.42 (2H, q, J = 7Hz),
3.64 (1H, t, J = 10Hz), 3.88 (1H, dd, J = 18Hz, 4Hz), 3.91 (1
H, m), 4.10 (1H, dd, J = 18Hz, 5Hz), 4.22 (2H, m), 4.40 (1H,
m), 4.47 (1H, dd, J = 12Hz, 5Hz), 4.52 (1H, m), 4.89 (1H,
d, J = 4Hz), 5.05 (1H, t, J = 10Hz), 5.1 (6H, m), 6.36 (1H, b
r), 6.42 (1H, br), 6.44 (1H, d, J = 7Hz), 6.57 (1H, d, J = 9H
z), 7.3-7.5 (18H, m), 7.77 (2H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [2R-
(8-Benzoylaminooctanoylamino) -4-carboxybutanoyl] -2-deoxy-3-O- (N-dodecanoylglycyl) -2-tetradecanoylamino-α-D-glucopyranoside In the above step 1, The obtained compound, 280 mg, was reduced in the same manner as in step 2 of Example 1 using 10% palladium carbon under a hydrogen stream, and similarly post-treated to obtain 140 mg of the title compound as a white powder.

[0063] _{[α] D + 30.1 ° (} c 0.6, chloroform - methanol (3: 1 (V / V ))). IR (KBr): 3320,1740,1640,1550,1205 cm -1 1 H- NMR (CDCl ₃ -CD ₃ OD (1: 1) / TMS): δ = 0.89 (6H, t, J = 7H
z), 1.20 (44H, s), 1.64 (8H, m), 2.02 (1H, m), 2.2-2.3 (7
H, m), 2.44 (2H, t, J = 7Hz), 2.67 (3H, m), 2.80 (1H, dd, J = 1
6Hz, 7Hz), 3.39 (2H, t, J = 7Hz), 3.64 (1H, t, J = 10Hz), 3.9
0 and 3.97 (each 1H, AB type d, J = 18Hz), 3.97 (1H, m),
4.16 (1H, dd, J = 11Hz, 4Hz), 4.34 (1H, dd, J = 12Hz, 5Hz), 4.
43 (2H, m), 4.52 (1H, dd, J = 8Hz, 6Hz), 4.99 (1H, d, J = 3Hz),
5.08 (1H, t, J = 10Hz), 7.4-7.5 (3H, m), 7.70 (2H, m).

Example 5 Step 1 2- (Diphenylphosphonoxy) ethyl 6-O- [4-benzyloxycarbonyl-2R- (tert-butoxycarbonylamino) butanoyl] -2-deoxy-3-O-tetradeca Noil-2-
Tetradecanoylamino-α-D-glucopyranoside 309 mg 2- (diphenylphosphonoxy) ethyl 2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino
-α-D-glucopyranoside and 137 mg of N-tert-butoxycarbonyl-D-glutamic acid γ-benzyl ester
It was dissolved in ml of dry methylene chloride, 4 mg of dimethylaminopyridine and 87 mg of dicyclohexylcarbodiimide were added under ice cooling, and the mixture was stirred for 45 minutes. After methanol was added to the reaction solution and stirred, the precipitated insoluble matter was removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent; chloroform containing 0.5% methanol) to give the title compound 2
97 mg was obtained as an oil.

[Α] _D + 27.2 ° (c 1.5, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, t, J = 7Hz), 1.25 (40H,
m), 1.43 (9H, s), 1.45-1.74 (m), 1.98 (1H, m), 2.04 (2H,
m), 2.18 (1H, m), 2.30 (2H, m), 2.48 (2H, m), 3.64 (2H,
m), 3.83 (1H, m), 3.90 (1H, m), 4.30 (3H, m), 4.40 (2H,
m), 4.48 (1H, m), 4.76 (1H, d, J = 3.5Hz), 5.07 (1H, t, J = 10
Hz), 5.12 (2H, m), 5.18 (1H, d, J = 7.5Hz), 6.41 (1H, d, J =
8.5Hz), 7.1-7.4 (15H, m).

Step 2 2- (Diphenylphosphonoxy) ethyl 6-O- (4-benzyloxycarbonyl-2R-tetradecanoylaminobutanoyl) -2-deoxy-3-O-tetradecanoyl-2-tetra Decanoylamino-α-D-glucopyranoside 280 mg of the compound obtained in the above step 1 was dissolved in 4 ml of dry methylene chloride, 4 ml of trifluoroacetic acid was added under ice cooling, and the mixture was stirred at the same temperature for 1.5 hours. The solvent was distilled off under reduced pressure, the residue was dissolved in chloroform, washed with water and a saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain an oily substance. On the other hand, 83 mg
Tetradecanoic acid and 49 mg 1-hydroxybenzotriazole were dissolved in 2 ml dry tetrahydrofuran,
Under ice cooling, 75 mg of dicyclohexylcarbodiimide was added, and the mixture was returned to room temperature and stirred for 2 hours or more. The reaction solution was added while insoluble matter precipitated in the oily matter was removed by filtration, and the mixture was stirred at room temperature for 17 hours. The residue obtained by evaporating the solvent under reduced pressure was purified by a silica gel column (developing solvent; chloroform containing 5% acetone) to give the title compound 217
Obtained mg as a white solid.

[Α] _D + 27.1 ° (c 1.4, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.28 (60H,
m), 1.94 (1H, m), 2.14-2.23 (3H, m), 2.33 (4H, m), 2.48
(2H, m), 3.67 (2H, m), 3.83 (1H, m), 3.89 (1H, m), 4.28 (2
H, m), 4.39 (2H, m), 4.49 (1H, dd, J = 12Hz, 4.5Hz), 4.55 (1
H, m), 4.76 (1H, d, J = 4Hz), 5.06 (1H, t, J = 10Hz), 5.12 (2
H, m), 6.34 (1H, d, J = 7.5Hz), 6.38 (1H, d, J = 10Hz), 7.2-
7.4 (15H, m).

Step 3 2-phosphonoxyethyl 6-O- (4-carboxy-2R-tetradecanoylaminobutanoyl) -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α -D-Glucopyranoside 205 mg of the compound obtained in the above step 2 was dissolved in a mixed solution of 30 ml of tetrahydrofuran and 1.5 ml of distilled water to give 60 mg.
Add 10% palladium on carbon at room temperature under a hydrogen atmosphere for 9
Stir for 0 minutes. Subsequently, 120 mg of platinum dioxide was added to this reaction liquid, and the mixture was further stirred at room temperature under a hydrogen atmosphere for 3 hours. The catalyst was removed by filtration, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol: water = 6: 4: 0.7). The obtained target product was tetrahydrofuran and water (9: 1).
It was dissolved in the mixed solvent of and was passed through a column packed with a strongly acidic ion exchange resin (manufactured by Dowex Co., 50W-X2, H type). The solvent was distilled off under reduced pressure and the obtained residue was suspended in dioxane and freeze-dried to obtain 112 mg of the title compound as a white powder. Melting point: 165-170 ° C (decomposition)

[0069] _{[α] D + 31.7 ° (} c 0.7, chloroform - methanol (3: 1 (V / V ))). IR (KBr): 3420, 1730, 1550, 1205 cm -1 1 H-NMR ( CDCl ₃ -CD ₃ OD (1: 1) / TMS): δ = 0.89 (9H, t, J = 7H
z), 1.28 (60H, bs), 1.59 (6H, m), 2.01 (1H, m), 2.17 (3H,
m), 2.27 (2H, m), 2.35 (2H, m), 2.43 (2H, m), 3.67 (2H,
m), 3.92 (2H, m), 4.19 (3H, m), 4.36 (1H, dd, J = 12Hz, 4.5H
z), 4.43 (1H, m), 4.49 (1H, dd, J = 8.5Hz, 6Hz), 4.80 (1H,
d, J = 3.5Hz), 5.16 (1H, dd, J = 10.5Hz, 9.5Hz).

Example 6 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (tert-Butoxycarbonylamino) butanoyl] -2-
Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl was prepared in the same manner as in Step 1 of Example 5.
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside and N-tertiary butoxycarbonyl-D-glutamic acid γ-benzyl ester were reacted to give the title compound as a colorless oil. I got it as a thing.

[Α] _D + 24.0 ° (c 0.4, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, J = 7.5Hz), 1.25 (br),
1.43 (9H, s), 1.5-1.7 (4H, m), 1.95 (m), 2.13 (3H, m),
2.31 (2H, m), 2.45 (2H, m), 2.65 (3H, m), 2.81 (1H, dd, J = 1
6.5Hz, 6Hz), 3.48 (1H, m), 3.64 (1H, m), 3.86 (1H, m),
4.35 (4H, m), 4.41 (1H, m), 4.49 (1H, m), 4.88 (1H, d, J = 3.
5Hz), 4.98 (1H, t, J = 10Hz), 5.11 (6H, m), 5.25 (1H, d, J =
7.5Hz), 6.25 (1H, d, J = 9.5Hz), 7.34 (15H, m).

Step 2 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [2R- (8-benzoylaminooctanoylamino) -4-benzyloxycarbonylbutanoyl] -2-deoxy- 3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above and 8-benzoylaminooctanoic acid were reacted in the same manner as in Step 2 of Example 5 to give the title compound. Was obtained as a white powder. Melting point: 104-107 ℃

[Α] _D + 22.4 ° (c 0.7, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, t, J = 7Hz), 1.25 (br),
1.50-1.75 (4H, m), 1.9-2.2 (6H, m), 2.31 (1H, m), 2.46
(1H, m), 2.62 (3H, m), 2.70 (1H, dd, J = 16Hz, 6Hz), 3.44 (2
H, m), 3.67 (1H, m), 3.87 (1H, m), 4.24 (2H, m), 4.41 (1H,
m), 4.50 (2H, m), 4.87 (1H, d, J = 3.5Hz), 5.00 (1H, t, J = 10H
z), 5.10 and 5.13 (total 6H, each s), 6.24 (1H, d, J = 10
Hz), 6.32 (1H, m), 6.46 (1H, d, J = 7.5Hz), 7.3-7.5 (18H,
m), 7.76 (2H, m).

Step 3 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [2R-
(8-Benzoylaminooctanoylamino) -4-carboxybutanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside Implement the compound obtained in step 2 above The reaction and post-treatment were carried out in the same manner as in Step 2 of Example 1 to obtain the title compound as a white powder.

[0075] [α] _D +40.0 DEG (c 0.1, methanol) IR (KBr):. 3350 , 1730, 1640, 1545 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.88 (6H, t, J = 7.5H
z), 1.25 (br), 1.5-1.7 (m), 2.02 (1H, m), 2.19 (3H, m),
2.26 (2H, m), 2.32 (2H, m), 2.45 (2H, t, J = 7.5Hz), 2.68 (3
H, m), 2.79 (1H, dd, J = 16.5Hz, 6Hz), 3.35 (2H, m), 3.63 (1
H, t, J = 9.5Hz), 3.97 (1H, m), 4.15 (1H, dd, J = 10.5Hz, 3.5H
z), 4.37 (2H, m), 4.44 (1H, m), 4.49 (1H, m), 4.97 (1H, d,
J = 3.5Hz), 5.07 (1H, t, J = 10.5Hz), 7.44 (2H, m), 7.50 (1
H, m), 7.80 (2H, m).

Example 7 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [2R- (6-benzoylaminohexanoylamino) -4-benzyloxycarbonylbutanoyl] -2 -Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 of Example 6 and 6-benzoylaminohexanoic acid were treated in the same manner as in Step 2 of Example 5. The reaction was carried out to give the title compound as a white powder. Melting point: 97-101 ℃

[Α] _D + 26.4 ° (c 0.9, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, m), 1.25 (br), 1.5-
1.8 (m), 1.9-2.5 (m), 2.62 (3H, m), 2.80 (1H, dd, J = 16Hz,
6Hz), 3.45 (2H, q, J = 6.5Hz), 3.66 (1H, t, J = 9.5Hz), 3.87
(1H, m), 4.18 (1H, m), 4.23 (1H, m), 4.40 (1H, m), 4.48 (2
H, m), 4.87 (1H, d, J = 3.5Hz), 5.01 (1H, t, J = 10Hz), 5.12
(6H, m), 6.26 (1H, d, J = 9.5Hz), 6.53 (1H, d, J = 7.5Hz), 6.
62 (1H, m), 7.3-7.5 (18H, m), 7.78 (2H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [2R-
(6-benzoylaminohexanoylamino) -4-carboxybutanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was carried out. The reaction was carried out in the same manner as in Step 2 of Example 1, and high performance liquid chromatography (used column; OD
S-type reverse phase column, developing solvent; methanol: water: acetic acid: triethylamine = 40: 1: 0.1: 0.15) and purified in the same manner to give the title compound as a white powder.

[0079] [α] _D +35.0 DEG (c 0.3, methanol) IR (KBr):. 3385 , 1730, 1645, 1540 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.88 (6H, m), 1.25
(br), 1.45 (2H, m), 1.57 (2H, m), 1.67 (2H, m), 2.02 (1H,
m), 2.18 (3H, m), 2.30 (4H, m), 2.45 (2H, t, J = 7.5Hz), 2.
68 (3H, m), 2.79 (1H, dd, J = 16.5Hz, 6Hz), 3.41 (2H, m), 3.
64 (1H, t, J = 9.5Hz), 3.97 (1H, m), 4.15 (1H, dd, J = 10.5H
z, 3.5Hz), 4.36 (2H, m), 4.44 (1H, m), 4.49 (1H, m), 4.97
(1H, d, J = 3.5Hz), 5.06 (1H, t, J = 10.5Hz), 7.44 (2H, m),
7.51 (1H, m), 7.81 (2H, m).

Example 8 Step 1 2-Methoxycarbonyl-1- (methoxycarbonylmethyl)
Ethyl 3,4,6-tri-O-acetyl-2- (8-benzoylaminooctanoylamino) -2-deoxy-α-D-glucopyranoside 1.096 g of 2-methoxycarbonyl-1- (methoxycarbonylmethyl) ethyl 3,4,6-tri-O-acetyl-2-deoxy
-2- (2,2,2-trichloroethoxycarbonylamino) -α-D
-Glucopyranoside was dissolved in 10 ml of acetic acid, and zinc powder was added little by little while stirring vigorously at room temperature until the raw material disappeared. The insoluble material was filtered off, and the residue was washed with chloroform, and the solvent of the filtrate was distilled off under reduced pressure. The operation of adding toluene to the residue and distilling off under reduced pressure was repeated, and the obtained residue was dissolved in chloroform and a 5% aqueous sodium hydrogencarbonate solution was
It was washed with saturated saline. After drying over anhydrous sodium sulfate,
The solvent was distilled off under reduced pressure to obtain an oily substance. 15 ml of this oil
Dissolved in dry methylene chloride, and 0.50 g of 8-benzoylaminooctanoic acid was added. Once ice-cooled, 0.39 g of dicyclohexylcarbodiimide and 20 mg of dimethylaminopyridine were added, and the mixture was returned to room temperature and stirred for 14 hours.
The precipitated insoluble material was removed by filtration, and the filtrate was diluted with 1N hydrochloric acid, 5
% Sodium hydrogencarbonate aqueous solution and saturated saline solution, and washed successively. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column (developing solvent; chloroform containing 5% acetone, changed from halfway to chloroform containing 2% methanol). Title compound 1.
162 g were obtained as a colorless viscous oil.

[Α] _D + 41.0 ° (c 1.5, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 1.36 (6H, m), 1.60 (2H, m), 1.7
0 (2H, m), 1.98 (3H, s), 2.02 (3H, s), 2.09 (3H, s), 2.20
(2H, m), 2.59 (1H, dd, J = 16Hz, 6.5Hz), 2.66 (2H, ABq), 2.
81 (1H, dd, J = 16Hz, 5.5Hz), 3.44 (2H, q, J = 7Hz), 3.69 (3H,
s), 3.72 (3H, s), 4.04 (1H, m), 4.10 (1H, dd, J = 12Hz, 2H
z), 4.20 (1H, dd, J = 12Hz, 4.5Hz), 4.35 (1H, td, J = 10Hz, 3.
5Hz), 4.41 (1H, m), 4.96 (1H, d, J = 4Hz), 5.09 (1H, t, J = 10
Hz), 5.14 (1H, t, J = 10Hz), 6.24 (1H, br), 6.34 (1H, d, J =
9Hz), 7.4-7.5 (3H, m), 7.76 (2H, m).

Step 2 2-Methoxycarbonyl-1- (methoxycarbonylmethyl)
Ethyl 2- (8-benzoylaminooctanoylamino) -2
-Deoxy-α-D-glucopyranoside 1.152 g of the compound of step 1 above was dissolved in 15 ml of dry methanol, and 18 mg of a sodium methoxide methanol solution prepared from metallic sodium was added under ice cooling, and the mixture was kept at the same temperature. Stir for 30 minutes. Non-aqueous strong acid ion exchange resin Amberlyst 15-E was added for neutralization, the resin was removed by filtration, and the solvent was distilled off under reduced pressure. The residue was treated with chloroform and hexane to solidify, and dried to obtain 827 mg of the title compound as a white solid. A part was recrystallized from a mixed solvent of hexane and chloroform. Melting point: 118-120 ° C

[0083] _{[α] D + 71.8 ° (} c 0.7, methanol) IR (KBr):. 3350,1740,1710,1645,1540,1030 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 1.36 (6H, m), 1.62 (4H, m), 2.3
1 (2H, t, J = 7Hz), 2.55 (1H, dd, J = 16Hz, 6Hz), 2.66 (2H,
m), 2.78 (1H, dd, J = 16Hz, 6.5Hz), 3.43 (2H, q, J = 7Hz), 3.
70 (3H, s), 3.73 (3H, s), 3.99 (1H, m), 4.43 (1H, m), 4.95
(1H, d, J = 4Hz), 6.34 (1H, br), 7.12 (1H, br), 7.4-7.5 (3
H, m), 7.75 (2H, m).

Step 3 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2- (8-benzoylaminooctanoylamino) -2-deoxy-α-D-glucopyranoside 616 mg of the compound obtained in Step 2 above Is dissolved in a mixed solution of 10 ml of tetrahydrofuran and 2 ml of water, and 3.17 ml of it is cooled with ice.
1N aqueous sodium hydroxide solution was added, and the mixture was stirred at the same temperature for 1 hour. Weakly acidic ion exchange resin MW for reaction liquid
C-1 was added for neutralization, the resin was removed by filtration and washed with ethanol. The solvent was distilled off under reduced pressure, and the procedure of adding ethanol and distilling off under reduced pressure was repeated, followed by vacuum drying in the presence of phosphorus pentoxide to obtain a yellow semisolid. This was dissolved in 8 ml of dried dimethylformamide, 0.88 ml of triethylamine and 0.75 ml of benzyl bromide were added, and the mixture was heated to 50-60 ° C and stirred for 1.5 hours. The solvent was evaporated under reduced pressure, the residue was dissolved in ethyl acetate, and washed with 1N hydrochloric acid, water and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column (developing solvent; chloroform containing 2% methanol, changed from the middle to 5%) to obtain 465 mg of the title compound. Obtained as a caramel-like colorless semi-solid.

[0085] _{[α] D + 16.1 ° (} c 1.0, chloroform) IR (KBr):. 3310,1735,1640,1540,1025 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 1.36 ( 6H, m), 1.61 (4H, m), 2.2
6 (2H, m), 2.58 (1H, dd, J = 16Hz, 6Hz), 2.66 (1H, dd, J = 16.5
Hz, 3.5Hz), 2.73 (1H, dd, J = 16.5Hz, 8.5Hz), 2.81 (1H, dd, J
= 16.5Hz, 6.5Hz), 3.42 (2H, m), 3.49 (1H, t, J = 9Hz), 3.59
(1H, t, J = 9.5Hz), 3.69 (2H, m), 3.81 (1H, m), 3.95 (1H, m),
4.45 (1H, m), 4.92 (1H, d, J = 3.5Hz), 5.13 (2H, s), 5.16
(2H, s), 6.19 (1H, br), 7.09 (1H, d, J = 7.5Hz), 7.3-7.5 (1
3H, m), 7.74 (2H, m).

Step 4 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2- (8-benzoylaminooctanoylamino) -2-deoxy-3-O-tetradecanoyl-α-D-glucopyranoside 571 mg of the compound obtained in step 3 was dissolved in 8 ml of dry methylene chloride, and 0.96 ml of 2,2-dimethoxypropane and 9 mg of camphorsulfonic acid were added at room temperature,
The mixture was stirred at room temperature for 4 hours. About 0.3% of triethylamine was added to the reaction mixture.
1 ml was added and stirred for neutralization, the reaction solution was washed with water and saturated saline and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained oily substance was dissolved in 10 ml of dry methylene chloride, 75 μl of pyridine, 5 mg of dimethylaminopyridine and 230 mg of tetradecanoic acid chloride were sequentially added under ice cooling, and the mixture was stirred at the same temperature for 3 hours. Furthermore, 0.31 ml of pyridine and 300 mg of acid chloride were added, and the mixture was returned to room temperature and stirred for 18 hours. The reaction mixture was washed successively with 1N hydrochloric acid, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained oily substance was
It was dissolved in 30 ml of 90% acetic acid aqueous solution, and heated and stirred at 90 ° C for 30 minutes. After cooling, the operation of distilling off the solvent under reduced pressure, adding toluene to the residue and distilling off the solvent under reduced pressure was repeated. The obtained residue was purified by a silica gel column (developing solvent; chloroform containing 5% acetone, changed from halfway to chloroform containing 2% methanol), solidified by adding hexane, and collected by filtration. Compound 633 mg was obtained as a white powder.

[Α] _D + 34.1 ° (c 1.3, chloroform) IR (KBr): 3340, 1735, 1650, 1635, 1540, 1150, 1030
^{. cm -1 1 H-NMR (} CDCl 3 / TMS): δ = 0.87 (3H, t, J = 7Hz), 1.24 (26H,
s), 1.62 (6H, m), 2.14 (2H, m), 2.32 (2H, m), 2.64 (3H,
m), 2.77 (1H, dd, J = 17Hz, 7Hz), 3.42 (2H, q, J = 6.5Hz), 3.
71 (4H, m), 4.23 (1H, td, J = 10Hz, 3.5Hz), 4.46 (1H, m), 4.
90 (1H, d, J = 3.5Hz), 4.96 (1H, dd, J = 10.5Hz, 9Hz), 5.10 (1
H, AB type d, J = 12Hz), 5.14 (2H, s), 5.15 (1H, AB type
d, J = 12Hz), 6.18 (1H, br), 6.33 (1H, d, J = 9Hz), 7.3-7.5
(13H, m), 7.75 (2H, m).

Step 5 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2- (8-benzoylaminooctanoylamino) -6-O- [4-benzyloxycarbonyl-2R- (tert
-Butoxycarbonylamino) butanoyl] -2-deoxy-
3-O-Tetradecanoyl-α-D-glucopyranoside The compound obtained in Step 4 above was reacted in the same manner as in Step 1 of Example 5 to give the title compound as a colorless viscous oil.

[Α] _D + 19.9 ° (c 0.9, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.87 (3H, t, J = 7Hz), 1.24 (26H,
s), 1.42 (9H, s), 1.60 (6H, m), 1.98 (1H, m), 2.13 (3H,
m), 2.30 (2H, m), 2.46 (2H, m), 2.64 (3H, m), 2.81 (1H, d
d, J = 16.5Hz, 6Hz), 3.42 (2H, q, J = 6.5Hz), 3.65 (1H, br),
3.86 (1H, m), 4.41 (1H, m), 4.88 (1H, d, J = 3.5Hz), 4.98
(1H, t, J = 10Hz), 5.11 (6H, m), 5.24 (1H, d ~ br), 6.16 (1H, b
r), 6.30 (1H, d, J = 9.5Hz), 7.3-7.5 (18H, m), 7.74 (2H,
m).

Step 6 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2- (8-benzoylaminooctanoylamino) -6-O- (4-benzyloxycarbonyl-2R-tetradecanoylaminobutane Noyl) -2-deoxy-3-O-tetradecanoyl-α-D-glucopyranoside The compound obtained in Step 5 above was reacted with tetradecanoic acid in the same manner as in Step 2 of Example 5 to give the title compound as a white wax. Obtained as a solid in the form of.

[Α] _D + 23.2 ° (c 0.9, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.87 (6H, m), 1.24 (46H, m), 1.
59 (8H, m), 2.04 (1H, m), 2.15 (5H, m), 2.31 (2H, m), 2.47
(2H, m), 2.64 (3H, m), 2.80 (1H, dd, J = 16Hz, 6Hz), 3.42 (2
H, q, J = 7Hz), 3.67 (1H, m), 3.87 (1H, m), 4.21 (2H, m),
4.41 (1H, m), 4.51 (2H, m), 4.89 (1H, d, J = 4Hz), 4.99 (1
H, t, J = 10Hz), 5.11 (6H, m), 6.16 (1H, br), 6.29 (1H, d, J =
9.5Hz), 6.36 (1H, d, J = 7.5Hz), 7.3-7.5 (18H, m), 7.74 (2
H, m).

Step 7 2-Carboxy-1- (carboxymethyl) ethyl 2- (8-benzoylaminooctanoylamino) -6-O- (4-carboxy-2R-tetradecanoylaminobutanoyl) -2-deoxy
-3-O-Tetradecanoyl-α-D-glucopyranoside The compound obtained in Step 6 above was reacted and worked up in the same manner as Step 2 of Example 1 to give the title compound as a white powder.

[0093] _{[α] D + 39.5 ° (} c 0.5, methanol) IR (KBr):. 3340,1730,1635,1545 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.89 (6H, m), 1.27
(46H, m), 1.60 (8H, m), 2.02 (1H, m), 2.15-2.4 (7H, m),
2.45 (2H, t, J = 7.5Hz), 2.66 (3H, m), 2.79 (1H, dd, J = 16Hz,
6.5Hz), 3.39 (2H, t, J = 7Hz), 3.66 (1H, t, J = 9.5Hz), 3.97
(1H, m), 4.15 (1H, dd, J = 11Hz, 3.5Hz), 4.38 (2H, m), 4.44
(1H, m), 4.49 (1H, dd, J = 8.5Hz, 6Hz), 4.97 (1H, d, J = 3.5H
z), 5.06 (1H, t, J = 10Hz), 7.46 (3H, m), 7.79 (2H, m).

Example 9 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2S- (tert-Butoxycarbonylamino) butanoyl] -2-
Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl was prepared in the same manner as in Step 1 of Example 5.
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside and N-tertiary butoxycarbonyl-L-glutamic acid γ-benzyl ester were reacted to give the title compound as a colorless oil. I got it as a thing.

[Α] _D + 22.7 ° (c 1.0, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, J = 7Hz), 1.25 (40H, b
r), 1.44 (9H, s), 1.61 (4H, m), 1.93 (1H, m), 2.10 (3H,
m), 2.31 (2H, m), 2.42 (2H, m), 2.66 (3H, m), 2.80 (1H, d
d, J = 16.5Hz, 6Hz), 3.63 (1H, m), 3.88 (1H, m), 4.26 (2H,
m), 4.4 (3H, m), 4.89 (1H, d, J = 3.5Hz), 5.00 (1H, t, J = 10H
z), 5.11 (6H, m), 5.20 (1H, d, J = 7.5Hz), 6.25 (1H, d, J = 9.
5Hz), 7.3-7.4 (15H, m).

Step 2 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (4-benzyloxycarbonyl-
2S-tetradecanoylaminobutanoyl) -2-deoxy-3-
O-tetradecanoyl-2-tetradecanoylamino-α-D-
Glucopyranoside The compound obtained in Step 1 above was reacted with tetradecanoic acid in the same manner as in Step 2 of Example 5 to obtain the title compound as a white waxy solid.

[Α] _D + 27.3 ° (c 1.9, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 6.5Hz), 1.25 (60
H, s), 1.59 (6H, m), 1.92 (1H, m), 2.13 (3H, m), 2.31 (4H,
m), 2.42 (2H, m), 2.66 (3H, m), 2.79 (1H, dd, J = 16.5Hz, 6H
z), 3.61 (1H, m), 3.88 (1H, m), 4.26 (2H, m), 4.36 (2H,
m), 4.61 (1H, m), 4.89 (1H, d, J = 3.5Hz), 5.01 (1H, m), 5.
1 (6H, m), 6.27 (1H, d, J = 9.5Hz), 6.34 (1H, d, J = 7Hz), 7.3
-7.4 (15H, m).

Step 3 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (4-
Carboxy-2S-tetradecanoylaminobutanoyl) -2-
Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in the above Step 2 was reacted in the same manner as in Step 2 of Example 1 and subjected to silica gel thin layer chromatography (developing solvent). Chloroform: methanol: 50% ammonium acetate aqueous solution = 6: 4: 0.5) and purified in the same manner to give the title compound as a white powder.

[0099] _{[α] D + 24.1 ° (} c 0.6, methanol) IR (KBr):. 3300 , 1660, 1470, 1170, 1055 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1 ) / TMS): δ = 0.89 (9H, t, J = 7H
z), 1.28 (60H, m), 1.60 (6H, m), 2.02 (1H, m), 2.20 (3H,
m), 2.23-2.39 (4H, m), 2.43 (2H, m), 2.65-2.71 (3H, m),
2.77 (1H, dd, J = 16Hz, 7Hz), 3.54 (1H, t, J = 10Hz), 3.99 (1
H, m), 4.13 (1H, dd, J = 11Hz, 4Hz), 4.30 (1H, dd, J = 12Hz, 5
Hz), 4.42-4.47 (2H, m), 4.52 (1H, dd, J = 9Hz, 5Hz), 4.97
(1H, d, J = 4Hz), 5.07 (1H, t, J = 10Hz).

Example 10 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 3-O-benzyloxycarbonyl-2-
Deoxy-2-tetradecanoylamino-α-D-glucopyranoside 2.32 g of 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside (15 ml) Dissolve it in dry methylene chloride, and add 2.04 ml of 2, 2-
Dimethoxypropane and 38 mg of camphorsulfonic acid were added, and the mixture was stirred at room temperature for 15 hours. Further, 20 mg of camphorsulfonic acid and 2.04 ml of 2,2-dimethoxypropane were added, and stirring was continued for 8 hours. Anhydrous potassium carbonate was added to the reaction solution, and the mixture was stirred and neutralized. The reaction solution was washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The yellow oil obtained was dissolved in 20 ml of dry methylene chloride and 0.40 ml of pyridine at room temperature,
0.61 g of N, N-dimethylaminopyridine and 0.71 ml of benzyloxycarbonyl chloride were sequentially added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was washed successively with 1N hydrochloric acid, water and saturated brine, and dried over anhydrous sodium sulfate.
The solvent was distilled off under reduced pressure, and the obtained yellow oily substance was added to 50 ml of 9
Dissolve in 0% acetic acid aqueous solution and heat with stirring at 90 ° C for 30 minutes.
After cooling, the operation of distilling off the solvent under reduced pressure, adding toluene to the residue and distilling off the solvent under reduced pressure was repeated. The obtained residue was purified by a silica gel column (developing solvent; chloroform containing 5% acetone and later changed to chloroform containing 2% methanol) to obtain a pale yellow oily substance. Hexane was added to this to crystallize and then collected by filtration to give the title compound 2.4.
2 g was obtained as a white solid. This solid could be recrystallized from hexane. Melting point: 80-82 ℃

[0102] _{[α] D + 46.5 ° (} c 0.8, chloroform) IR (KBr):. 3350 , 1750, 1730, 1650, 1275, 1260 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (3H, t, J = 7Hz), 1.22 (20H,
s), 1.52 (2H, m), 2.0-2.1 (2H, m), 2.64 (3H, m), 2.77 (1
H, dd, J = 16Hz, 6Hz), 3.75 (4H, m), 4.26 (1H, td, J = 10Hz, 3H
z), 4.46 (1H, m), 4.82 (1H, dd, J = 11Hz, 8Hz), 4.92 (1H, d,
J = 4Hz), 5.10 (1H, AB type d, J = 12Hz), 5.13 (4H, s), 5.1
4 (1H, AB type d, J = 12Hz), 6.31 (1H, d, J = 9Hz), 7.3-7.4
(15H, m).

Step 2 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 3-O-benzyloxycarbonyl-6-O
-[3-Benzyloxycarbonyl-2R, 3R-bis (tetradecanoyloxy) propanoyl] -2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was prepared as in Example 1. Reaction with 2,3-bis-O-tetradecanoyl-L-tartaric acid monobenzyl ester as in Step 1 gave the title compound as a colorless viscous oil.

[Α] _D + 27.8 ° (c 1.0, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (60H,
m), 1.54 (6H, m), 2.04 (2H, m), 2.11 (1H, m), 2.26 (1H,
m), 2.39 (2H, m), 2.65 (3H, m), 2.77 (1H, dd, J = 16Hz, 6H
z), 3.60 (1H, td, J = 9.5Hz, 5Hz), 3.85 (1H, m), 4.20 (1H, d
d, J = 12Hz, 2Hz), 4.28 (1H, m), 4.42 (1H, m), 4.49 (1H, dd,
J = 12Hz, 4Hz), 4.79 (1H, dd, J = 10.5Hz, 9.5Hz), 4.90 (1H,
d, J = 3.5Hz), 5.14 (8H, m), 5.70 (1H, d, J = 3Hz), 5.76 (1H,
d, J = 3Hz), 6.23 (1H, t, J = 10Hz), 7.3-7.4 (20H, m).

Step 3 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [3-
Carboxy-2R, 3R-bis (tetradecanoyloxy) propanoyl] -2-deoxy-2-tetradecanoylamino-α
-D-Glucopyranoside The compound obtained in Step 2 above was reacted and worked up in the same manner as in Step 2 of Example 1 to obtain the title compound as a white powder.

[0105] _{[α] D + 40.7 ° (} c 0.5, methanol) IR (KBr):. 3450,1740,1220,1150 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.89 (12H, t, J = 6.5
Hz), 1.27 (60H, s), 1.64 (6H, m), 2.28 (2H, m), 2.44 (4H,
m), 2.66 (3H, m), 2.78 (1H, dd, J = 16Hz, 6.5Hz), 3.41 (1H,
t, J = 9.5 Hz), 3.56 (1H, t, J = 10Hz), 3.86 (1H, m), 3.96 (1
H, dd, J = 10.5Hz, 3.5Hz), 4.39 (2H, m), 4.46 (1H, d, J = 11H
z), 4.94 (1H, d, J = 3.5Hz), 5.78 (2H, s) .1H-NMR (CD
Cl3 / TMS): δ = 0.88 (3H, t, J = 7Hz), 1.22 (20H, s), 1.52 (2
H, m), 2.0-2.1 (2H, m), 2.64 (3H, m), 2.77 (1H, dd, J = 16H
z, 6Hz), 3.75 (4H, m), 4.26 (1H, td, J = 10Hz, 3Hz), 4.46 (1
H, m), 4.82 (1H, dd, J = 11Hz, 8Hz), 4.92 (1H, d, J = 4Hz), 5.
10 (1H, AB type d, J = 12Hz), 5.13 (4H, s), 5.14 (1H, AB t
ype d, J = 12Hz), 6.31 (1H, d, J = 9Hz), 7.3-7.4 (15H, m).

Step 2 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 3-O-benzyloxycarbonyl-6-O
-[3-Benzyloxycarbonyl-2R, 3R-bis (tetradecanoyloxy) propanoyl] -2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was prepared as in Example 1. Reaction with 2,3-bis-O-tetradecanoyl-L-tartaric acid monobenzyl ester as in Step 1 gave the title compound as a colorless viscous oil.

[Α] _D + 27.8 ° (c 1.0, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (60H,
m), 1.54 (6H, m), 2.04 (2H, m), 2.11 (1H, m), 2.26 (1H,
m), 2.39 (2H, m), 2.65 (3H, m), 2.77 (1H, dd, J = 16Hz, 6H
z), 3.60 (1H, td, J = 9.5Hz, 5Hz), 3.85 (1H, m), 4.20 (1H, d
d, J = 12Hz, 2Hz), 4.28 (1H, m), 4.42 (1H, m), 4.49 (1H, dd,
J = 12Hz, 4Hz), 4.79 (1H, dd, J = 10.5Hz, 9.5Hz), 4.90 (1H, d,
J = 3.5Hz), 5.14 (8H, m), 5.70 (1H, d, J = 3Hz), 5.76 (1H, d,
J = 3Hz), 6.23 (1H, t, J = 10Hz), 7.3-7.4 (20H, m).

Step 3 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [3-
Carboxy-2R, 3R-bis (tetradecanoyloxy) propanoyl] -2-deoxy-2-tetradecanoylamino-α
-D-Glucopyranoside The compound obtained in Step 2 above was reacted and worked up in the same manner as in Step 2 of Example 1 to obtain the title compound as a white powder.

. [0109] _{[α] D +40 7 ° (} c 0.5, methanol) IR (KBr):. 3450,1740,1220,1150 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.89 (12H, t, J = 6.5
Hz), 1.27 (60H, s), 1.64 (6H, m), 2.28 (2H, m), 2.44 (4H,
m), 2.66 (3H, m), 2.78 (1H, dd, J = 16Hz, 6.5Hz), 3.41 (1H,
t, J = 9.5 Hz), 3.56 (1H, t, J = 10Hz), 3.86 (1H, m), 3.96 (1
H, dd, J = 10.5Hz, 3.5Hz), 4.39 (2H, m), 4.46 (1H, d, J = 11H
z), 4.94 (1H, d, J = 3.5Hz), 5.78 (2H, s).

Example 11 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 3-O- (8-benzoylaminooctanoyl) -2-deoxy-2-tetradecanoylamino-α-D -Glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl as in Step 4 of Example 8
2-Deoxy-2-tetradecanoylamino-α-D-glucopyranoside was isopropylidened, and then reacted with 8-benzoylaminooctanoic acid, and then the isopropylidene group was removed to give the title compound as a colorless oil. Obtained.

[Α] _D + 33.6 ° (c 0.5, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.87 (3H, t, J = 7.5Hz), 1.23 (b
r), 1.36 (br), 1.62 (br), 2.12 (2H, m), 2.32 (2H, m), 2.
58-2.82 (4H, m), 3.43 (2H, q, J = 7.5Hz), 3.7-3.8 (4H, m),
4.23 (1H, td, J = 9.5Hz, 4Hz), 4.45 (1H, m), 4.90 (1H, d, J = 4
Hz), 5.01 (1H, m), 5.13 (4H, m), 6.31 (2H, m), 7.3-7.8 (15
H, m).

Step 2 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 3-O- (8-benzoylaminooctanoyl) -6-O- [4-benzyloxycarbonyl-2R- (tert-butoxy Carbonylamino) butanoyl] -2-deoxy-2-
Tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was treated in the same manner as in Step 1 of Example 5 to give N-tert-butoxycarbonyl-D-glutamic acid γ-
Reaction with benzyl ester gave the title compound as a colorless oil.

[Α] _D + 22.2 ° (c 0.5, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (3H, J = 7.5Hz), 1.25 (br),
1.43 (9H, s), 1.5-1.7 (4H, m), 1.95 (1H, m), 2.13 (2H,
m), 2.32 (2H, m), 2.44 (2H, m), 2.65 (3H, m), 2.81 (1H, d
d, J = 16.5Hz, 6Hz), 3.44 (2H, m), 3.65 (1H, m), 3.87 (1H,
m), 4.24 (3H, m), 4.42 (2H, m), 4.86 (1H, d, J = 3.5Hz), 5.
00 (1H, t, J = 10Hz), 5.13 (6H, m), 5.27 (1H, d ~ br), 6.28 (2
H, m), 7.3-7.5 (18H, m), 7.75 (2H, m).

Step 3 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 3-O- (8-benzoylaminooctanoyl) -6-O- (4-benzyloxycarbonyl-2R-tetradecanoylamino Butanoyl) -2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 above and tetradecanoic acid were reacted in the same manner as in Step 2 of Example 5 to give the title compound as a white powder. Obtained. Melting point: 84-86 ℃

[Α] _D + 25.3 ° (c 0.9, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, m), 1.25 (br), 1.50-
1.65 (4H, m), 2.0-2.5 (m), 2.62 (3H, m), 2.82 (1H, dd, J = 1
6Hz, 6Hz), 3.43 (2H, q, J = 7Hz), 3.68 (1H, m), 3.88 (1H,
m), 4.23 (2H, m), 4.40 (1H, m), 4.46 (1H, m), 4.53 (1H,
m), 4.87 (1H, d, J = 3.5Hz), 5.02 (1H, t, J = 10Hz), 5.12 (6
H, m), 6.27 (1H, d, J = 9.5Hz), 6.37 (1H, m), 6.42 (1H, d, J =
7.5Hz), 7.3-7.5 (18H, m), 7.76 (2H, m).

Step 4 2-Carboxy-1- (carboxymethyl) ethyl 3-O- (8-
Benzoylaminooctanoyl) -6-O- (4-carboxy-2R
-Tetradecanoylaminobutanoyl) -2-deoxy-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 3 above was reacted, purified and post-treated in the same manner as in Step 2 of Example 7. The title compound was obtained as a white powder.

[0117] [α] _D +45.2 ° (c0.3, methanol) IR (KBr):. 3355 , 1730, 1635, 1580 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.88 (6H, m), 1.25
(br), 1.5-1.7 (m), 2.02 (1H, m), 2.15-2.40 (m), 2.45 (2
H, t, J = 7.5Hz), 2.68 (3H, m), 2.79 (1H, dd, J = 16.5Hz, 6H
z), 3.39 (2H, m), 3.64 (1H, t, J = 9.5Hz), 3.97 (1H, m), 4.
15 (1H, dd, J = 10.5Hz, 3.5Hz), 4.37 (2H, m), 4.44 (1H, m),
4.50 (1H, m), 4.97 (1H, d, J = 2.5Hz), 5.06 (1H, t, J = 10.5H
z), 7.44 (2H, m), 7.50 (1H, m), 7.80 (2H, m).

Example 12 Step 1 2-Methoxycarbonyl-1- (methoxycarbonylmethyl)
Ethyl 3,4,6-tri-O-acetyl-2-deoxy-2-tetradecanoylamino-β-D-glucopyranoside 2-methoxycarbonyl-1- (methoxycarbonylmethyl)
Ethyl 3,4,6-tri-O-acetyl-2-deoxy-2- (2,2,2-
Trichloroethoxycarbonylamino) -β-D-glucopyranoside was reacted with tetradecanoic acid as in Step 1 of Example 8 to give the title compound as a white waxy solid.

[0119] [alpha] _D -3.1 ° (c 1.9, chloroform) IR (KBr):. 3560 , 3330, 1745, 1660 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (3H, t , J = 7Hz), 1.25 (br),
1.54 (2H, m), 2.00 (3H, s), 2.02 (3H, s), 2.07 (2H, m),
2.08 (3H, s), 2.5-2.65 (3H, m), 2.92 (1H, dd, J = 16.5Hz, 5H
z), 3.67 (3H, s), 3.68 (3H, s), 4.00 (1H, q, J = 9Hz), 4.10
(1H, dd, J = 11Hz, 2.5Hz), 4.24 (1H, dd, J = 11Hz, 5Hz), 4.40
(1H, m), 4.47 (1H, m), 4.77 (1H, d, J = 9Hz), 5.05 (1H, t, J =
9.5Hz), 5.12 (1H, t, J = 9.5Hz), 5.62 (1H, d, J = 9Hz).

Step 2 2-Methoxycarbonyl-1- (methoxycarbonylmethyl)
Ethyl 2-deoxy-2-tetradecanoylamino-β-D-
Glucopyranoside The compound obtained in Step 1 above was reacted in the same manner as in Step 2 of Example 8 to give the title compound as a white powder.

¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (3H, t, J = 7H
z), 1.25 (br), 1.63 (2H, m), 2.2-2.35 (2H, m), 2.49-2.7
7 (5H, m), 2.81 (1H, dd, J = 15.5Hz, 7Hz), 3.38-3.57 (4H,
m), 3.73 (3H, s), 3.74 (3H, s), 3.92 (1H, dd, J = 12Hz.2.5H
z), 4.45 (1H, m), 4.58 (1H, d, J = 8.5Hz), 6.90 (1H, br).

Step 3 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-2-tetradecanoylamino-β-D-glucopyranoside The compound obtained in Step 2 above was processed in Step 3 of Example 8. The reaction was performed in the same manner as in (1) to give the title compound as a white waxy solid.

[0123] _{[α] D -23.9 ° (c} 1.0, chloroform) IR (KBr):. 3430 , 3320, 1740, 1655, 1550 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (3H , t, J = 7Hz), 1.25 (br),
1.61 (2H, m), 2.21 (2H, m), 2.56 (1H, dd, J = 16Hz, 5.5Hz),
2.65 (1H, dd, J = 16Hz, 3.5Hz), 2.74 (1H, m), 2.82 (1H, dd,
J = 16.5Hz, 6.5Hz), 3.25-3.45 (4H, m), 3.59 (1H, m), 3.83
(1H, dd, J = 12Hz, 3.5Hz), 4.00 (1H, q, J = 9Hz), 4.20 (2H,
m), 5.08-5.24 (4H, m), 6.84 (1H, m), 7.35 (10H, m).

Step 4 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2-deoxy-3-O-tetradecanoyl-
2-Tetradecanoylamino-β-D-glucopyranoside The compound obtained in Step 3 above was reacted in the same manner as in Step 4 of Example 8 to give the title compound as a white powder.

[0125] _{[α] D -18.9 ° (c} 1.3, chloroform) IR (KBr):. 3340 , 1750, 1730, 1670 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (3H, t , J = 7Hz), 1.25 (br),
1.50 (2H, m), 1.57 (2H, m), 1.99 (2H, m), 2.32 (3H, m),
2.51 (1H, dd, J = 15.5Hz, 6Hz), 2.56 (1H, dd, J = 16.5Hz, 3.5H
z), 2.65 (1H, dd, J = 16.5Hz, 9.5Hz), 2.79 (1H, dd, J = 15.5H)
z, 7Hz), 3.34 (1H, m), 3.49 (1H, t, J = 9.5Hz), 3.59 (1H,
m), 3.87 (2H, m), 4.51 (1H, m), 4.53 (1H, d, J = 8.5Hz), 4.
80 (1H, dd, J = 10.5Hz, 8.5Hz), 5.02 (1H, AB type d, J = 12H
z), 5.13 (1H, AB type d, J = 12.5Hz), 5.14 (1H, AB type
d, J = 12.5Hz), 5.22 (1H, AB type d, J = 12Hz), 5.38 (1H, d,
J = 9Hz), 7.3-7.4 (10H, m).

Step 5 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (tert-Butoxycarbonylamino) butanoyl] -2-
Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranoside The compound obtained in Step 4 above was reacted in the same manner as in Step 1 of Example 5 to give the title compound as a colorless wax. Got as.

[0127] _{[α] D -10.3 ° (c} 0.6, chloroform) IR (KBr):. 3360 , 1730, 1670, 1535 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (6H, t , J = 7Hz), 1.25 (br),
1.42 (9H, s), 1.45-1.6 (4H, m), 1.98 (3H, m), 2.14 (1H,
m), 2.31 (2H, m), 2.4-2.6 (3H, m), 2.87 (1H, dd, J = 16.5H
z, 5Hz), 3.48 (1H, m), 3.63 (1H, m), 3.88 (1H, m), 4.26 (2
H, m), 4.41 (1H, m), 4.49 (1H, m), 4.53 (1H, d, J = 8.5Hz),
4.83 (1H, t, J = 10Hz), 5.01 (1H, AB type d, J = 12Hz), 5.10
(4H, m), 5.20 (1H, AB type d, J = 12Hz), 5.30 (1H, d, J = 9H
z), 7.34 (15H, m).

Step 6 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (4-benzyloxycarbonyl-
2R-tetradecanoylaminobutanoyl) -2-deoxy-3-
O-tetradecanoyl-2-tetradecanoylamino-β-D-
Glucopyranoside The compound obtained in Step 5 above was reacted with tetradecanoic acid in the same manner as in Step 2 of Example 5 to give the title compound as a white powder. Melting point: 107-109 ℃

[0129] _{[α] D -8.8 ° (c} 0.6, chloroform) IR (KBr):. 3340 , 1740, 1670, 1625, 1550 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (9H , t, J = 7Hz), 1.25 (br),
1.5-1.75 (6H, m), 1.9-2.6 (m), 2.87 (1H, dd, J = 16Hz, 5H
z), 3.40 (1H, m), 3.64 (1H, t, J = 9.5Hz), 3.89 (1H, m), 4.
29 (1H, m), 4.4-4.5 (3H, m), 4.52 (1H, d, J = 8.5Hz), 4.83
(1H, t, J = 10Hz), 5.01 (1H, AB type d, J = 12Hz), 5.11 (4H,
m), 5.20 (1H, AB type d, J = 12Hz), 5.32 (1H, d, J = 9Hz),
6.47 (1H, d, J = 7Hz), 7.34 (15H, m).

Step 7 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (4-
Carboxy-2R-tetradecanoylaminobutanoyl) -2-
Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-β-D-glucopyranoside The compound obtained in Step 6 above was reacted, purified and post-treated in the same manner as in Step 3 of Example 9 to give the title compound. Was obtained as a white powder. Melting point: 204-205 ℃ (decomposition)

[0131] _{[α] D -7.0 ° (c} 0.2, methanol) IR (KBr):. 3380,1730,1660,1620,1550 cm -1 1 H-NMR (DMSO-d6 / TMS): δ = 0.86 ( 9H, t, J = 7Hz), 1.24 (b
r), 1.35-1.5 (m), 1.62-2.02 (m), 2.08-2.31 (m), 2.42-
2.5 (m), 2.59 (1H, dd, J = 16.5Hz.6.5Hz), 3.55 (1H, m), 3.
78 (1H, m), 3.83 (1H, m), 4.13 (1H, m), 4.26 (1H, m), 4.31
(2H, m), 4.60 (1H, d, J = 8Hz), 4.87 (1H, t, J = 10.5Hz), 5.
33 (1H, d), 12.09 (3H, s).

Example 13 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (4-Octanoylaminobenzoylamino) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in step 1 of example 6 was carried out. Reacting with p-octanoylaminobenzoic acid as in Step 2 of Example 5,
The title compound was obtained as a white powder.

[0133] _{[α] D + 24.5 ° (} c 0.9, chloroform) IR (KBr):. 3320 , 1740, 1660, 1620 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (9H, m), 1.25 (br), 1.9-
2.65 (m), 2.78 (1H, dd, J = 16.5Hz, 6.5Hz), 3.68 (1H, m),
3.88 (1H, m), 4.21 (2H, m), 4.40 (1H, m), 4.53 (1H, m), 4.
67 (1H, m), 4.87 (1H, d, J = 3.5Hz), 4.98 (1H, t, J = 10Hz),
5.10 (6H, m), 6.27 (1H, d, J = 9.5Hz), 7.3-7.4 (19H, m), 7.
61 (1H, d, J = 8.5Hz), 7.77 (1H, d, J = 8.5Hz).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [4-
Carboxy-2R- (4-octanoylaminobenzoylamino) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-
Tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was reacted, purified and post-treated in the same manner as in Step 2 of Example 7 to obtain the title compound as a white powder. It did not show a clear melting point and was colored brown near 195 ° C.

[0135] _{[α] D + 30.1 ° (} c 0.3, methanol) IR (KBr):. 3320 , 1730, 1660, 1525 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.90 (9H, m), 1.28
(br), 1.60 (4H, m), 1.72 (2H, m), 2.2-2.4 (m), 2.5-2.65
(m), 2.75 (1H, dd, J = 17.5Hz, 6Hz), 3.64 (1H, t, J = 9.5Hz),
3.98 (1H, m), 4.14 (1H, dd, J = 11Hz, 3.5Hz), 4.40 (3H, m),
4.96 (1H, d, J = 3.5Hz), 5.06 (1H, t, J = 10.5Hz), 7.69 (2H,
d, J = 9Hz), 7.84 (2H, d, J = 9Hz).

Example 14 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (4-Octanoylaminophenylacetamido) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in step 1 of example 6 was carried out. It was reacted with p-octanoylaminophenylacetic acid in the same manner as in Step 2 of Example 5 to obtain the title compound as a white waxy solid.

[0137] _{[α] D + 20.5 ° (} c 0.8, chloroform) IR (KBr):. 3310 , 1740, 1650, 1630, 1610 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 ( 9H, t, J = 7Hz), 1.25 (br),
1.55-1.75 (m), 1.95-2.45 (m), 2.67 (1H, m), 2.76 (1H, d
d, J = 16Hz, 6.5Hz), 3.45 (2H, q, J = 6.5Hz), 3.50 (3H, m),
3.84 (1H, m), 4.02 (1H, m), 4.19 (1H, m), 4.43 (1H, m), 4.
47 (1H, m), 4.54 (1H, m), 4.92 (1H, d, J = 4Hz), 5.01 (1H, t,
J = 10Hz), 5.03-5.16 (6H, m), 6.12 (1H, d, J = 9Hz), 6.39 (1
H, d, J = 9Hz), 6.62 (1H, m), 7.20 (2H, d, J = 9Hz), 7.34 (15
H, m), 7.67 (2H, d, J = 9Hz), 8.51 (1H, s).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [4-
Carboxy-2R- (4-octanoylaminophenylacetamido) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was used as an example. The reaction, purification, and post-treatment were performed in the same manner as in Step 2 of 7 to obtain the title compound as a white powder. Melting point: 165-173 ° C (decomposition)

[0139] _{[α] D + 39.6 ° (} c 0.3, methanol) IR (KBr):. 3300 , 1730, 1660, 1535 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.88 (9H, m), 1.27
(br), 1.57 (4H, m), 1.71 (2H, m), 2.02 (1H, m), 2.20 (3H,
m), 2.35 (6H, m), 2.61 (1H, dd, J = 16Hz, 6Hz), 2.65 (2H, d,
J = 6Hz), 2.76 (1H, dd, J = 16Hz, 6Hz), 3.55 (2H, s), 3.60 (1
H, t, J = 9.5Hz), 3.95 (1H, m), 4.14 (1H, dd, J = 11Hz, 3.5H
z), 4.36 (2H, m), 4.41 (1H, m), 4.50 (1H, m), 4.95 (1H, d, J
= 3.5Hz), 5.06 (1H, t, J = 10.5Hz), 7.25 (2H, d, J = 8.5Hz),
7.54 (2H, d, J = 8.5Hz).

Example 15 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (4-benzyloxycarbonyl-
2R-tetradecanoylaminobutanoyl) -2-deoxy-3-
O-tetradecanoyl-2-tetradecanoylamino-α-D-
Glucopyranoside The compound obtained in Step 1 of Example 6 was reacted with tetradecanoic acid in the same manner as in Step 2 of Example 5 to obtain the title compound as a white waxy solid.

[Α] _D + 18.1 ° (c 0.9, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (60H,
m), 1.59 (4H, m), 1.67 (2H, m), 1.93 (1H, m), 1.98-2.21
(5H, m), 2.30 (2H, m), 2.44 (2H, m), 2.62 (3H, m), 2.81 (1
H, dd, J = 16Hz, 6Hz), 3.67 (1H, t, J = 10Hz), 3.88 (1H, m),
4.24 (2H, m), 4.41 (1H, m), 4.51 (2H, m), 4.89 (1H, d, J = 3.
5Hz), 4.99 (1H, t, J = 10Hz), 5.12 (4H, m), 6.24 (1H, d, J = 9
Hz), 6.35 (1H, d, J = 7Hz), 7.2-7.4 (15H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (4-
Carboxy-2R-tetradecanoylaminobutanoyl) -2-
Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was reacted, purified and post-treated in the same manner as in Step 3 of Example 9 to give the title compound. Was obtained as a white powder.

[0143] _{[α] D + 41.3 ° (} c 0.6, methanol) IR (KBr):. 3290 , 1730, 1060 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS) : δ = 0.90 (9H, t, J = 7H
z), 1.29 (60H, s), 1.55-1.62 (6H, m), 1.98 (1H, m), 2.20
(3H, m), 2.25 (2H, m), 2.31 (2H, m), 2.43 (2H, m), 2.70 (3
H, m), 2.76 (1H, dd, J = 15Hz, 7Hz), 3.62 (1H, t, J = 10Hz),
3.97 (1H, m), 4.12 (1H, dd, J = 11Hz, 4Hz), 4.32 (1H, dd, J =
12Hz, 4Hz), 4.42 (1H, m), 4.43 (1H, m), 4.48 (1H, dd, J = 9H
z, 6Hz), 4.99 (1H, d, J = 3.5Hz), 5.06 (1H, dd, J = 11Hz, 9H
z).

Example 16 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 2- (8-benzoylaminooctanoylamino) -6-O- [4-benzyloxycarbonyl-2R- (N -Dodecanoyl-N-dodecylglycylamino) butanoyl] -2
-Deoxy-3-O-tetradecanoyl-α-D-glucopyranoside The compound obtained in Step 5 of Example 8 was reacted with N-dodecyl-N-dodecanoylglycine in the same manner as in Step 2 of Example 5. , The title compound was obtained as a colorless oil.

[Α] _D + 21.6 ° (c 1.3, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.87 (9H, t, J = 7Hz), 1.25 (60H,
m), 1.60 (10H, m), 2.03 (1H, m), 2.15 (3H, m), 2.30 (2H,
m), 2.36 (2H, m), 2.43 (2H, m), 2.62 (3H, m), 2.81 (1H, d
d, J = 16Hz, 6Hz), 3.31 (2H, m), 3.42 (2H, q, J = 6.5Hz), 3.
69 (1H, m), 3.88 (1H, m), 3.91 and 3.97 (each 1H, AB typ
ed, J = 12Hz), 4.25 (2H, m), 4.41 (2H, m), 4.48 (1H, m),
4.88 (1H, d, J = 3.5Hz), 5.00 (1H, t, J = 10Hz), 5.10 (6H,
m), 6.18 (1H, br), 6.28 (1H, d, J = 9.5Hz), 7.14 (1H, d, J =
7.5 Hz), 7.3-7.5 (18H, m), 7.75 (2H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 2- (8-benzoylaminooctanoylamino) -6-O- [4-carboxy-2R- (N-dodecanoyl-N-dodecylglycylamino) ) Butanoyl] -2-deoxy-3-O-tetradecanoyl-α-D-glucopyranoside The compound obtained in the above Step 1 was reacted, purified and post-treated in the same manner as in Step 3 of Example 9 to give the title compound as a white compound. Obtained as a powder.

[0147] _{[α] D + 36.0 ° (} c 0.4, methanol) IR (KBr):. 3320,1740,1700,1665,1645,1545 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1 : 1) / TMS): δ = 0.88 (9H, m), 1.27
(60H, m), 1.59 (10H, m), 2.03 (1H, m), 2.19 (3H, m), 2.31
(2H, m), 2.43 (4H, m), 2.66 (3H, m), 2.79 (1H, dd, J = 16Hz,
6.5Hz), 3.39 (4H, m), 3.63 (1H, t, J = 9.5Hz), 3.98 (1H,
m), 3.99 and 4.06 (each 1H, AB type d, J = 16Hz), 4.15
(1H, dd, J = 10.5Hz, 4Hz), 4.35 (1H, dd, J = 11.5Hz, 4.5Hz),
4.43 (2H, m), 4.53 (1H, dd, J = 8.5Hz, 5.5Hz), 4.97 (1H, d,
J = 4Hz), 5.07 (1H, t, J = 10Hz), 7.46 (3H, m), 7.79 (2H,
m).

Example 17 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (8-Phenyloctanoylamino) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 of Example 6 was used as Example. It was reacted with 8-phenyloctanoic acid in the same manner as in Step 2 of 5 to obtain the title compound as a white powder. Melting point: 68-70 ° C

[0149] _{[α] D + 25.3 ° (} c 2.2, chloroform) IR (KBr):. 3530 , 3320, 1735, 1650 cm -1 1 H-NMR (CDCl 3 / TMS): δ = 0.88 (6H, t, J = 7Hz), 1.25 (br),
1.55-1.70 (m), 1.9-2.7 (m), 2.81 (1H, dd, J = 16.5Hz, 6.5
Hz), 3.68 (1H, m), 3.89 (1H, m), 4.25 (2H, m), 4.42 (1H,
m), 4.46 (1H, m), 4.60 (1H, m), 4.63 (1H, m), 4.90 (1H, d,
J = 3.5Hz), 5.00 (1H, t, J = 10Hz), 5.12 (6H, m), 6.26 (1H,
d, J = 9.5Hz), 6.37 (1H, d, J = 7Hz), 7.15-7.4 (20H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [4-
Carboxy-2R- (8-phenyloctanoylamino) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was used in Example 7 The reaction, purification, and post-treatment were performed in the same manner as in Step 2 of 1. to give the title compound as a white powder. It did not show a clear melting point and was colored brown around 135 ° C.

[0151] _{[α] D + 41.0 ° (} c 0.4, methanol) IR (KBr):. 3300 , 1740, 1650, 1545 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.89 (6H, t, J = 7H
z), 1.28 (br), 1.60 (m), 2.03 (1H, m), 2.15-2.40 (m), 2.
43 (2H, t, J = 7.5Hz), 2.60 (2H, t, J = 7.5Hz), 2.66 (3H, m),
2.78 (1H, dd, J = 17.5Hz, 6Hz), 3.61 (1H, t, J = 9.5Hz), 3.99
(1H, m), 4.15 (1H, dd, J = 11Hz, 3.5Hz), 4.32-4.50 (4H, m),
4.97 (1H, d, J = 3.5Hz), 5.07 (1H, t, J = 10.5Hz), 7.15-7.2
8 (5H, m).

Example 18 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [4-benzyloxycarbonyl-
2R- (4-octylbenzoylamino) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino
-α-D-Glucopyranoside The compound obtained in Step 1 of Example 6 was reacted with p-octylbenzoic acid in the same manner as in Step 2 of Example 5 to obtain the title compound as a colorless oil.

[Α] _D + 12.9 ° (c 0.5, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (br),
1.55-1.7 (m), 1.95-2.35 (m), 2.5-2.65 (m), 2.67 (1H,
m), 2.79 (1H, dd, J = 16Hz, 6.5Hz), 3.72 (1H, m), 3.89 (1H,
m), 4.27 (2H, m), 4.43 (1H, m), 4.55 (1H, dd, J = 12Hz, 4H
z), 4.68 (1H, m), 4.90 (1H, d, J = 4Hz), 5.00 (1H, t, J = 10H
z), 5.11 (6H, m), 6.24 (1H, d, J = 9.5Hz), 7.22 (2H, d, J = 9H
z), 7.34 (15H, m), 7.70 (2H, d, J = 9Hz).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- [4-
Carboxy-2R- (4-octylbenzoylamino) butanoyl] -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was used in Example 7. Reaction, purification, and post-treatment were carried out in the same manner as in Step 2 to obtain the title compound as a white powder. It did not show a clear melting point and was colored brown near 173 ° C.

[0155] _{[α] D + 37.9 ° (} c 0.4, methanol) IR (KBr):. 1730 , 1640, 1540 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS) : δ = 0.88 (9H, t), 1.27
(br), 1.60 (m), 2.15-2.35 (m), 2.53 (2H, t, J = 7.5Hz),
2.57-2.70 (m), 2.75 (1H, dd, J = 16Hz, 6Hz), 3.65 (1H, t, J =
9.5Hz), 3.97 (1H, m), 4.14 (1H, dd, J = 11Hz, 3.5Hz), 4.41
(3H, m), 4.96 (1H, d, J = 3.5Hz), 5.06 (1H, t, J = 10.5Hz),
7.28 (2H, d, J = 8.5Hz), 7.78 (2H, d, J = 8.5Hz).

Example 19 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (3-benzyloxycarbonyl-
3S-tetradecanoylaminopropanoyl) -2-deoxy-
3-O-tetradecanoyl-2-tetradecanoylamino-α-D
-Glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl in the same manner as in Step 1 of Example 5.
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside and N-tetradecanoyl-L
-Aspartic acid α-benzyl ester was reacted to give the title compound as a colorless oil.

[Α] _D + 31.1 ° (c 0.8, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7.5Hz), 1.25 (60
H, s), 1.58 (6H, m), 2.12 (2H, m), 2.20 (2H, m), 2.31 (2H,
m), 2.63 (3H, m), 2.74 (1H, dd, J = 16Hz, 8Hz), 2.79 (1H, d
d, J = 16Hz, 6Hz), 2.90 (1H, dd, J = 15Hz, 4Hz), 3.74 (1H, m),
3.84 (1H, m), 4.18 (1H, dd, J = 12Hz, 2Hz), 4.27 (2H, m), 4.
40 (1H, m), 4.91 (1H, d, J = 3Hz), 5.01 (2H, m), 5.12 (4H,
m), 5.17 and 5.23 (each 1H, AB type d, J = 12Hz), 6.24
(1H, d, J = 9Hz), 6.38 (1H, d, J = 9Hz), 7.36 (15H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (3-
Carboxy-3S-tetradecanoylaminopropanoyl)-
2-Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The title compound was obtained by reacting, purifying, and post-treating the compound obtained in the above Step 1 in the same manner as in Step 3 of Example 9. The compound was obtained as a white powder.

[0159] [α] _D +35.6 ° (C0.6, methanol) IR (KBr):. 3430 , 1730, 1180 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS ): δ = 0.89 (9H, t, J = 6H
z), 1.28 (60H, s), 1.50-1.68 (6H, m), 2.23 (4H, m), 2.32
(2H, m), 2.66 (3H, m), 2.77 (1H, dd, J = 14Hz, 6Hz), 2.95 (2
H, m), 3.62 (1H, t, J = 10Hz), 3.96 (1H, m), 4.15 (1H, m),
4.32 (1H, dd, J = 12Hz, 4Hz), 4.42 (2H, m), 4.83 (1H, m), 4.
99 (1H, d, J = 3Hz), 5.07 (1H, t, J = 10Hz).

Example 20 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (3-benzyloxycarbonyl-
3S-tetradecanoyloxypropanoyl) -2-deoxy-
3-O-tetradecanoyl-2-tetradecanoylamino-α-D
-Glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl in the same manner as in Step 1 of Example 5.
2-Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside and O-tetradecanoyl-L
-The malic acid α-benzyl ester was reacted to give the title compound as a colorless oil.

[Α] _D + 15.9 ° (c 1.2, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (60H,
s), 2.12 (2H, m), 2.30 (2H, m), 2.36 (2H, m), 2.66 (3H,
m), 2.79 (1H, dd, J = 16Hz, 6Hz), 2.81 (2H, m), 3.58 (1H,
m), 3.83 (1H, m), 4.24 (2H, m), 4.36 (1H, dd, J = 12Hz, 4H
z), 4.42 (1H, m), 4.89 (1H, d, J = 4Hz), 4.98 (1H, t, J = 10H
z), 5.00 (4H, m), 5.15 and 5.21 (each 1H, AB type d, J =
12Hz), 5.54 (1H, dd, J = 8Hz, 5Hz), 6.24 (1H, d, J = 9Hz),
7.34 (15H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (3-
Carboxy-3S-tetradecanoyloxypropanoyl)-
2-Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The title compound was obtained by reacting, purifying, and post-treating the compound obtained in the above Step 1 in the same manner as in Step 3 of Example 9. The compound was obtained as a white powder.

[0163] [α] _D +27.8 ° (C0.6, methanol) IR (KBr):. 3390 , 1740, 1170 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS ): δ = 0.90 (9H, t, J = 6H
z), 1.29 (60H, s), 1.50-1.68 (6H, m), 2.20 (2H, t, J = 7H
z), 2.31 (2H, m), 2.40 (2H, t, J = 7Hz), 2.67 (3H, m), 2.77
(2H, dd, J = 16Hz, 6Hz), 2.93 (1H, dd, J = 17Hz, 8Hz), 3.00 (1
H, dd, J = 17Hz, 4Hz), 3.55 (1H, t, J = 10Hz), 3.96 (1H, m),
4.11 (1H, dd, J = 10Hz, 3Hz), 4.33 (1H, m), 4.41 (2H, m), 4.
99 (1H, d, J = 3Hz), 5.06 (1H, t, J = 10Hz), 5.42 (1H, m).

Example 21 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [3-benzyloxycarbonyl-
2S- (tert-Butoxycarbonylamino) propanoyl] -2
-Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl was prepared in the same manner as in Step 1 of Example 5.
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside and N-tertiary butoxycarbonyl-L-aspartic acid β-benzyl ester were reacted to give the title compound as a colorless compound. Obtained as an oil.

[Α] _D + 27.5 ° (c 0.8, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.86 (6H, t, J = 6Hz), 1.24 (40H,
br), 1.44 (9H, s), 1.56 (4H, m), 2.12 (2H, m), 2.29 (2H,
m), 2.63 (3H, m), 2.79 (1H, m), 2.88 (1H, m), 3.05 (1H, d
d, J = 17Hz, 4Hz), 3.55 (1H, m), 3.85 (1H, m), 4.22 (2H,
m), 4.40 (1H, m), 4.47 (1H, dd, J = 12Hz, 4Hz), 4.58 (1H,
m), 4.83 (1H, d, J = 4Hz), 4.98 (1H, t, J = 10Hz), 5.13 (6H,
m), 5.51 (1H, d, J = 7.5Hz), 6.22 (1H, d, J = 9.5Hz), 7.3-7.
4 (15H, m).

Step 2 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (3-benzyloxycarbonyl-
2S-tetradecanoylaminopropanoyl) -2-deoxy-
3-O-tetradecanoyl-2-tetradecanoylamino-α-D
-Glucopyranoside The compound obtained in Step 1 above was reacted with tetradecanoic acid in the same manner as in Step 2 of Example 5 to obtain the title compound as a white wax-like solid.

[Α] _D + 28.8 ° (c 0.7, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (60H,
br), 1.56 (6H, m), 2.04-2.22 (4H, m), 2.27 (2H, m), 2.6
2 (3H, m), 2.77 (1H, dd, J = 16Hz, 6Hz), 2.90 (1H, dd, J = 17H
z, 4Hz), 3.06 (1H, dd, J = 17Hz, 4Hz), 3.55 (1H, t, J = 10Hz),
3.85 (1H, m), 4.21 (1H, td, J = 10Hz, 4Hz), 4.27 (1H, dd, J =
12Hz, 2Hz), 4.40 (1H, m), 4.44 (1H, dd, J = 12Hz, 4Hz), 4.8
2 (1H, d, J = 4Hz), 4.86 (1H, m), 5.00 (1H, t, J = 10Hz), 5.14
(6H, m), 6.28 (1H, d, J = 9Hz), 6.52 (1H, d, J = 8Hz), 7.3-7.
4 (15H, m).

Step 3 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (3-
Carboxy-2S-tetradecanoylaminopropanoyl)-
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in the above Step 2 was reacted, purified and post-treated in the same manner as in Step 3 of Example 9, The title compound was obtained as a white powder.

[0169] _{[α] D + 29.4 ° (} c 0.5, methanol) IR (KBr):. 1730 , 1220 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.90 (9H, m), 1.29
(60H, br), 1.60 (6H, m), 2.18-2.38 (6H, m), 2.61-2.77 (4
H, m), 2.83 (1H, dd, J = 17Hz, 7Hz), 2.88 (1H, dd, J = 17Hz, 5H
z), 3.56 (1H, t, J = 10Hz), 3.95 (1H, m), 4.10 (1H, dd, J = 10
Hz, 3Hz), 4.32 (1H, dd, J = 12Hz, 4Hz), 4.42 (2H, m), 4.83
(1H, m), 4.98 (1H, d, J = 3Hz), 5.06 (1H, t, J = 10Hz).

Example 22 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- [3-benzyloxycarbonyl-
2R- (tert-Butoxycarbonylamino) propanoyl] -2
-Deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl was prepared in the same manner as in Step 1 of Example 5.
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside and N-tertiary butoxycarbonyl-D-aspartic acid β-benzyl ester were reacted to give the title compound as a colorless compound. Obtained as an oil.

[Α] _D + 22.3 ° (c 1.2, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, t, J = 6.5Hz), 1.24 (40
H, br), 1.44 (9H, s), 2.30 (2H, m), 2.63 (3H, m), 2.79 (1
H, m), 2.85 (1H, m), 3.00 (1H, dd, J = 17Hz, 4Hz), 3.58 (1H,
m), 3.84 (1H, m), 4.21 (1H, m), 4.24 (2H, m), 4.51 (1H,
m), 4.58 (1H, m), 4.88 (1H, d, J = 4Hz), 4.98 (1H, J = 9.5H
z), 5.11 (6H, m), 5.52 (1H, d, J = 7.5Hz), 6.24 (1H, d, J = 9.
5Hz), 7.3-7.4 (15H, m).

Step 2 2-benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- (3-benzyloxycarbonyl-
2R-tetradecanoylaminopropanoyl) -2-deoxy-
3-O-tetradecanoyl-2-tetradecanoylamino-α-D
-Glucopyranoside The compound obtained in Step 1 above was reacted with tetradecanoic acid in the same manner as in Step 2 of Example 5 to obtain the title compound as a white wax-like solid.

[Α] _D + 19.3 ° (c 0.6, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (9H, t, J = 7Hz), 1.25 (60H,
br), 1.58 (6H, m), 2.09-2.19 (4H, m), 2.32 (2H, m), 2.6
0 (3H, m), 2.79 (1H, m), 2.89 (1H, dd, J = 16Hz, 4Hz), 3.04
(1H, dd, J = 16Hz, 5Hz), 3.55 (1H, m), 3.84 (1H, m), 4.20
(1H, m), 4.25 (1H, m), 4.42 (1H, m), 4.53 (1H, dd, J = 12Hz,
4Hz), 4.83 (1H, m), 4.87 (1H, d, J = 3.5Hz), 4.98 (1H, t, J =
10Hz), 5.11 (6H, m), 6.23 (1H, d, J = 9Hz), 6.44 (1H, d, J = 8
Hz), 7.3-7.4 (15H, m).

Step 3 2-Carboxy-1- (carboxymethyl) ethyl 6-O- (3-
Carboxy-2R-tetradecanoylaminopropanoyl)-
2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 2 above was reacted, purified and post-treated in the same manner as in Step 3 of Example 9 to give The title compound was obtained as a white powder.

[0175] _{[α] D + 46.1 ° (} c 0.6, methanol) IR (KBr):. 3360 , 1740, 1180 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS) : δ = 0.90 (9H, t, J = 7H
z), 1.29 (60H, br), 1.59 (6H, m), 2.20 (2H, m), 2.25 (2H,
m), 2.31 (2H, m), 2.66 (3H, m), 2.74 (1H, dd, J = 16Hz, 7H
z), 2.84 (1H, dd, J = 17Hz, 7Hz), 2.88 (1H, dd, J = 17Hz, 5H
z), 3.59 (1H, t, J = 10Hz), 3.96 (1H, dt, J = 10Hz, 3Hz), 4.1
1 (1H, dd, J = 11Hz, 3Hz), 4.34-4.46 (3H, m), 4.79 (1H, t, J =
6Hz), 4.97 (1H, d, J = 3Hz), 5.06 (1H, dd, J = 11Hz, 9Hz).

Example 23 Step 1 2-Benzyloxycarbonyl-1- (benzyloxycarbonylmethyl) ethyl 6-O- {4-benzyloxycarbonyl-
2R- [6- (4-Ethylphenyl) hexanoylamino] butanoyl} -2-deoxy-3-O-tetradecanoyl-2-tetradecanoylamino-α-D-glucopyranoside Obtained in Step 1 of Example 6 This compound was reacted with 6- (4-ethylphenyl) hexanoic acid in the same manner as in Step 2 of Example 5 to give the title compound as a colorless oil.

[Α] _D + 23.1 ° (c 0.5, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (6H, t, J = 7Hz), 1.25 (br),
1.60 (m), 2.0-2.7 (m), 2.80 (1H, dd, J = 16Hz, 6.5Hz), 3.
74 (1H, m), 3.88 (1H, m), 4.23 (2H, m), 4.41 (1H, m), 4.48
(1H, m), 4.52 (1H, m), 4.88 (1H, d, J = 4Hz), 4.99 (1H, t, J =
10Hz), 5.10 (6H, m), 6.25 (1H, d, J = 9.5Hz), 6.37 (1H, d, J
= 7Hz), 7.1-7.4 (19H, m).

Step 2 2-Carboxy-1- (carboxymethyl) ethyl 6-O- {4-
Carboxy-2R- [6- (4-ethylphenyl) hexanoylamino] butanoyl} -2-deoxy-3-O-tetradecanoyl-
2-Tetradecanoylamino-α-D-glucopyranoside The compound obtained in Step 1 above was reacted, purified and post-treated in the same manner as in Step 2 of Example 7 to obtain the title compound as a white powder. It did not show a clear melting point and was colored brown near 147 ° C.

[0179] _{[α] D + 44.3 ° (} c 0.5, methanol) IR (KBr):. 3380 , 1735, 1650, 1545 cm -1 1 H-NMR (CDCl 3 -CD 3 OD (1: 1) / TMS): δ = 0.88 (6H, t), 1.27
(br), 1.60 (m), 2.0-2.35 (m), 2.43 (2H, t, J = 7.5Hz), 2.
55-2.67 (m), 2.77 (1H, dd, J = 16Hz, 6Hz), 3.63 (1H, t, J = 9.
5Hz), 3.97 (1H, m), 4.15 (1H, dd, J = 11Hz, 3.5Hz), 4.37
(m), 4.43 (1H, m), 4.47 (1H, m), 4.96 (1H, d, J = 3.5Hz), 5.
07 (1H, t, J = 10.5Hz), 7.09 (4H, s).

Reference Example 3 N-Tetradecanoyl-L-aspartic acid α-benzyl ester 447 mg of L-aspartic acid α-benzyl ester
It was suspended in ml of water, and 1.34 g of sodium hydrogen carbonate was added and dissolved. Under ice cooling, 1.09 ml of tetradecanoic acid chloride was added, and the mixture was returned to room temperature and stirred for 4 hours. In addition, 0.
81 ml of tetradecanoic acid chloride was added, and the mixture was stirred at room temperature for 10 hours. Hydrochloric acid was added to acidify the reaction solution, which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column (developing solvent; chloroform containing 2% methanol). Further, recrystallization from a mixed solvent of ether and hexane gave 432 mg of the title compound. Melting point: 78-80 ° C

[Α] _D + 23.6 ° (c 0.6, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (3H, t, J = 7Hz), 1.24 (20H,
s), 1.59 (2H, m), 2.22 (2H, t, J = 7Hz), 2.85 (1H, dd, J = 7H
z, 4Hz), 3.07 (1H, dd, J = 7Hz, 4Hz), 4.92 (1H, m), 5.17

(1H, d, J = 12Hz), 5.20 (1H, d, J = 13Hz), 6.62
(1H, d, J = 8Hz), 7.3-7.37 (5H, m). Reference Example 4 O-tetradecanoyl-L-malic acid α-benzyl ester L-malic acid α-benzyl was prepared in the same manner as in Reference Example 1. Phenacyl esterification of the ester followed by reaction with tetradecanoic acid chloride and finally removal of the phenacyl group gave the title compound as a colorless oil.

[Α] _D −16.5 ° (c 1.0, chloroform) ¹ H-NMR (CDCl ₃ / TMS): δ = 0.88 (3H, t, J = 7Hz), 1.25 (20H,
m), 1.60 (2H, m), 2.36 (2H, m), 2.92 (2H, d, J = 6Hz), 5.16
and 5.21 (each 1H, AB type d, J = 12Hz), 5.52 (1H, t, J = 6
Hz), 7.3-7.4 (5H, m).

Test Example Monocytes (5.0 ×) isolated from a healthy subject and isolated from blood to which heparin was added using a specific gravity separation liquid.
10 ⁴ cells / well) were used. Monocytes are 0, 1, 10 and
100 ng / ml LPS (E. coli 0127: B8 DIFCO) and 0.5,
The cells were cultured for 4 hours in RPMI-1640 medium supplemented with 10% fetal bovine serum (0.5 ml / well) supplemented with 5 and 50 ng / ml of the test compound. The TNF activity in the culture supernatant was measured by a cytotoxicity test for L929 cells. The results are shown in Table 3.

[0185]

[Table 3]

From these results, it was confirmed that the compound of the present invention used in the test suppressed the induction of TNF by endotoxin (LPS) in an extremely small amount.

The compounds of the present invention have low toxicity. For example, when the compounds of Examples 1 to 3 were intravenously administered to mice through the tail vein, no abnormality was observed at 200 μg per mouse.

The compound of the present invention is useful as a prophylactic / therapeutic agent for multiple organ failure, and particularly, it can be expected to have an excellent effect in the prevention / treatment of endotoxin-induced multiple organ failure syndrome. The standard dose is 0.1 to 30 mg / day for adults, given intravenously, but the dose may be adjusted according to the patient's condition. Subcutaneous administration and oral administration are also possible. The compound of the present invention can be made into various preparations, for example, injection preparations, by a usual preparation technique using isotonic agents, stabilizers and other additives.

Claims (7)

[Claims] 1. The general formula I: And a salt thereof. The symbols in the formula have the following definitions. R ¹ represents a substituent —CO—Z ¹ —N (Z ¹¹ ) —CO—Z ² —H or a substituent —CO—Z ³ —H. R ² is a substituent group -CO-Z ⁴ -N (Z ¹² ) -CO-
Z ⁵ -H means a substituent -CO-Z ⁶ -H or a hydrogen atom. Q ¹ means a carboxyl group or a phosphonoxy group. Q ² means a carboxyl group or a phosphonoxy group. Q ³ represents a hydrogen atom, a carboxyl group or a phosphonoxy group. Y ¹ means an alkylene group having 1 to 10 carbon atoms, which may have one or more substituents —0COR ¹¹ and / or substituents —NHCOR ¹² . m means an integer of 0 to 20. n means an integer of 0 to 20. R ¹¹ represents the substituent —Z ¹³ or the substituent —Z ⁷ —N (Z ¹⁴ ) —CO—Z ⁸ —H. R ¹² is a substituent group -Z ¹⁵ or a substituent group -Z ⁹ -N (Z ¹⁶ ) -CO-Z ¹⁰
-H means. Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ , Z ⁶ , Z ⁷ , Z ⁸ , Z ⁹ and Z ¹⁰
Means a combination of an alkylene group having 1 to 20 carbon atoms and a phenylene group, or one of them. Z ¹¹ , Z ¹² , Z ¹³ ,
Z ¹⁴ , Z ¹⁵ and Z ¹⁶ are each an alkyl group having 1 to 20 carbon atoms which may be substituted by a phenyl group, and a carbon number
1 to 20 carbon atoms which may contain a phenyl group and a phenylene group which may be substituted by an alkyl group 1 to 20 carbon atoms
It means 20 alkylene groups or hydrogen atoms. 2. Q ¹ , Q ² and Q ³ are carboxyl groups, R ¹ is a tetradecanoyl group, R ² is an N-dodecanoylglycyl group, and m and n are 1. Item 1 compound 3. Q ¹ , Q ² and Q ³ are carboxyl groups, R ¹ is a tetradecanoyl group, R ² is an N-dodecanoylglycyl group, and Y ¹ is tetradecanoyloxy. A carboxyalkyl group having a group and / or a tetradecanoylamino group in the side chain, and m and n are 1; 4. Q ¹ , Q ² and Q ³ are carboxyl groups, R ¹ is a tetradecanoyl group, R ² is an N-dodecanoylglycyl group, and Y ¹ is tetradecanoyloxy. Group and / or a phosphonoxyalkyl group having a tetradecanoylamino group in the side chain thereof, and m and n are 1; 5. Q ¹ , Q ² and Q ³ are carboxyl groups, R ¹ is a benzoylaminoalkyl group, R ² is an N-dodecanoylglycyl group, and m and n are 1. Item 1 compound 6. Q ¹ , Q ² and Q ³ are carboxyl groups, R ¹ is an N-dodecanoylsarcosyl group, R ² is an N-dodecanoylglycyl group, and m and n are 1 The compound of claim 1 which is 7. Q ¹ is a carboxyl group, Q ² is a phosphonoxy group, Q ³ is a hydrogen atom, m 1 is 1,
The compound according to claim 1, wherein n is 0, R ¹ and R ² are tetradecanoyl groups, and Y ¹ is an ethylene group or a propylene group having a tetradecanoylamino group and / or a tetradecanoyloxy group.