JPH11269189A - Compound having immunomodulative activity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a compound expressed by a specific structural formula and useful as therapeutic agents for marrow suppression caused by the administration of antitumor agents and anticancer agents based on their immunopotentiative actions and radiation therapy, inflammatory diseases, immunodeficiency diseases and autoimmunodeficiency diseases such as chronic rheumatoid arthritis as an immunomodulator. SOLUTION: This compound is expressed by a structural formula: a monosaccharide → Gall → 1' Cer (C24, Sat.). The monsaccharide is bound to 3, 4 and 6 positions of Gal with glycoside bonds and preferably selected from the group comprising Fuc, Gal, and Rha. The compound is preferably expressed by the structural formula: Fuc β1 → 3Gal α1 → 1' Cer (C24, Sat.), Fuc β1 →4 (Fuc α1 → 3) Gal α1 → 1' Cer (C24, Sat.), Fuc β1 → 6 Gal α1 → 1' Cer (C24, Sat.), or the like. The compound is preferably administered in a daily dose of 0.1-100 mg for an adult.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a glycosphingolipid compound having an immunomodulatory activity, in particular, an immunostimulatory activity and an antitumor activity.

[0002]

2. Description of the Related Art With cancer always occupying the top of adult diseases, the search for compounds having immunostimulatory activity and antitumor activity has always been an issue.
Recently, it has been discovered that glycosphingolipids derived from marine animals have immunostimulatory activity and antitumor activity, and glycosphingolipids having higher activity have been synthesized with reference to the structure thereof (Japanese Patent Laid-Open No. 5-205). 59081 and JP-A-5-9193).

JP-A-5-59081 and JP-A-5-9193 disclose a glycosphingolipid in which ceramide is glycosidically bound to galactose as the best compound. Then, in order to improve the water solubility of the compound, a monosaccharide is added to the galactose portion (WO94 / 24142), but in such a case, no increase in activity has been observed.

[0004]

SUMMARY OF THE INVENTION A series of inventions in this field have a primary purpose of enhancing the activity of a compound, in which case the compound is designed to have a higher immunostimulatory activity and antitumor activity. Is required to be designed. The present inventors have found that the activity may be increased by regioselectively adding a monosaccharide, which was not found to increase the activity in the above literature, and completed the present invention. .

[0005] More specifically, according to the present invention, there are provided the following compounds and medicaments.

(1) Monosaccharide → Gal1 → 1′Cer (C2
4, Sat.).

(2) The compound according to (1), wherein the monosaccharide has a glycosidic bond at the 3-position of Gal.

(3) The compound according to (2), wherein the monosaccharide is selected from the group consisting of Fuc, Gal, and Rha.

(4) The compound according to (1), wherein the monosaccharide has a glycosidic bond at the 4-position of Gal.

(5) The compound according to (4), wherein the monosaccharide is selected from the group consisting of Fuc, Gal, and Rha.

(6) The compound according to (1), wherein the monosaccharide has a glycosidic bond at position 6 of Gal.

(7) The compound according to (6), wherein the monosaccharide is selected from the group consisting of Fuc, Gal, and Rha.

(8) Fucβ1 → 3Galα1 → 1 ′
A compound represented by the structural formula of Cer (C24, Sat.).

(9) Fucβ1 → 4 (Fucα1 →
3) A compound represented by the structural formula Galα1 → 1′Cer (C24, Sat.).

(10) Fucβ1 → 6Galα1 → 1
'A compound represented by the structural formula of Cer (C24, Sat.).

(11) Galβ1 → 6Galα1 → 1
'A compound represented by the structural formula of Cer (C24, Sat.).

(12) Rhaα1 → 6Galα1 → 1
'A compound represented by the structural formula of Cer (C24, Sat.).

(13) Rhaα1 → 6Galβ1 → 1
'A compound represented by the structural formula of Cer (C24, Sat.).

(14) Galβ1 → 6Galα1 → 1
'A compound represented by the structural formula of Cer (C24, Sat.).

(15) The compound according to any one of (1) to (14), or Rhaα1 → 6Galβ1 → 1
A medicament containing an effective amount of a compound represented by the structural formula of 'Cer (double bond between C24 and C4-C5).

(16) The medicament according to (15), which is an immunomodulator.

(17) The medicament according to (15), which is an immunostimulant.

(18) The medicament according to (15), which is an antitumor agent. In addition, (C24, Sat.) Having 24 carbon atoms indicates that the compound is a saturated compound.

[0024]

BEST MODE FOR CARRYING OUT THE INVENTION As shown in the experimental examples described below, the compound of the present invention exhibits a lymphocyte proliferation promoting action, that is, an immunostimulatory activity in a mouse lymphocyte blastogenesis reaction. It can be used as a therapeutic agent for myelosuppression caused by administration of antitumor agents and anticancer agents and radiation therapy, and as a therapeutic agent for various infectious diseases and immunodeficiencies. Further, since it acts on immunocompetent cells, it can be used as an immunomodulator, for example, as a therapeutic drug for autoimmune diseases such as rheumatoid arthritis.

The compound of the present invention as a medicament can be administered by any suitable route of administration, specifically, in the case of animals, intraperitoneal administration, subcutaneous administration, intravenous administration to a vein or artery, and local administration by injection. In the case of human, intravenous administration, intraarterial administration, local administration by injection, intraperitoneal / pleural cavity administration, oral administration, subcutaneous administration, intramuscular administration, sublingual administration, transdermal absorption or rectal administration Can be administered. When administering the compound of the present invention as a drug, depending on the administration method and administration purpose, injections, suspensions, tablets, granules,
It can be administered in the form of powders, capsules, ointments, creams and the like. To make these preparations, solvents,
Solubilizing agents, isotonic agents, preservatives, antioxidants, excipients, binders, lubricants, stabilizers and the like can be added. As the solvent, for example, water, physiological saline and the like, as the solubilizer, for example, ethanol, polysorbates, cremophor, and the like, and as the excipient, for example, lactose, starch, crystalline cellulose, mannitol, maltose, phosphorus Calcium hydrogen oxylate, light anhydrous silicic acid, calcium carbonate, etc., as a binder, for example, starch, polyvinylpyrrolidone,
Hydroxypropylcellulose, ethylcellulose, carboxymethylcellulose, gum arabic, etc., as disintegrants, for example, starch, carboxymethylcellulose calcium, etc., as lubricants, for example, magnesium stearate, talc, hardened oil, etc., as stabilizers For example, lactose, mannitol, maltose, polysorbates, macrogol, polyoxyethylene hydrogenated castor oil and the like. Also, if necessary, glycerin, dimethylacetamide, 70% sodium lactate, a surfactant, a basic substance (for example, sodium hydroxide, ethylenediamine, ethanolamine, sodium carbonate,
Arginine, meglumine, trisaminomethane). Using these components, injections, tablets, granules,
It can be manufactured into a dosage form such as a capsule. The dose of the compound of the present invention is determined in consideration of the results of animal experiments and various situations so that the total dose does not exceed a certain amount when administered once or repeatedly. The specific dosage depends on the method of administration, the condition of the patient or the treated animal, for example, age,
Needless to say, it will vary according to body weight, gender, sensitivity, diet (diet), administration time, concomitant drug, patient or the degree of the disease. Must be determined by a specialist's dosage determination test. Specifically, the dose is about 0.01 mg to 400 mg, preferably about 0.1 mg to 100 mg per adult day.

[0026]

EXAMPLES <Example 1> A solution of compound 1 (1.25 g, 5 mmol) in dimethylformamide (10 mL) was stirred at 0 ° C, and 60% sodium hydride (0.33 g, 8.3 mmol) was slowly added. After the generation of hydrogen gas is completed, benzyl bromide (0.59
mL, 7.5 mmol) and stirred at room temperature for 4.5 hours. After the reaction solution was quenched with methanol, the solvent was distilled off under reduced pressure, and the residue was extracted with chloroform. The organic layer was dried over magnesium sulfate after washing with saturated aqueous sodium hydrogen carbonate and saturated brine. The residue was purified by a silica gel column (toluene: ethyl acetate = 4: 1 to 1: 1) to give compound 2 (461 mg, 21%) and compound 3 (167 mg, 8%).
Compound 4 (246 mg, 11%) was obtained. Compound 2 (V. Pozsgay, Bioconjugate Chem. , 1996, 7,
45-55) Rf = 0.27 (toluene: ethyl acetate = 1: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.43 to 7.20 (5H, m, Arom.H),
4.843 (1H, d, J = 11.7Hz, CH2 Ph), 4.741 (1H, d, J =
11.7Hz, CH ₂ Ph), 4.333 (1H, d, J = 9.5Hz, H-1), 4.2
60 (1H, t, J = 5.8Hz, H-3), 4.207 (1H, dd, J = 2.2, 5.
5Hz, H-4), 3.461 (1H, dd, J = 6.3, 9.5Hz, H-2), 2.19
8 (3H, s, SMe), 1.449, 1.357 (6H, 2S, 2Me) Compound 3 Rf = 0.37 (toluene: ethyl acetate = 1: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.43 to 7.20 (5H, m, Arom.H),
4.645 (1H, d, J = 12.1Hz, CH ₂ Ph), 4.557 (1H, d, J =
12.1Hz, CH ₂ Ph), 4.225 (1H, dd, J 2.2, = 5.5Hz, H-
4), 4.165 (1H, d, J = 10.3Hz, H-1), 4.057 (1H, t, J =
5.9Hz, H-3), 3.576 (1H, dd, J = 7.3, 10.3Hz, H-2),
2.215 (3H, s, SMe), 1.515, 1.356 (6H, 2S, 2Me) Compound 4 Rf = 0.81 (toluene: ethyl acetate = 1: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.43 to 7.20 (10H, m, Arom.H),
4.843 (1H, d, J = 11.3Hz, CH ₂ Ph), 4.741 (1H, d, J =
11.3Hz, CH ₂ Ph), 4.629 (1H, d, J = 11.7Hz, CH ₂ Ph),
4.542 (1H, d, J = 11.7Hz, CH ₂ Ph), 4.323 (1H, d, J =
9.5Hz, H-1), 3.906 (1H, br-t, J = 5.1Hz, H-5), 3.451
(1H, dd, J = 6.2, 9.9Hz, H-2), 2.195 (3H, s, SMe),
1.438, 1.351 (6H, 2S, 2Me)

Example 2 To Compound 2 (363 mg, 1.1 mmol) was added pyridine (10 mL), acetic anhydride (10 mL), and a catalytic amount of 4-dimethylaminopyridine, and the mixture was stirred at room temperature overnight. The solvent was azeotropically distilled with toluene, and the residue was purified with a silica gel column (toluene:
Ethyl acetate = 5: 3) Purified and compound 5 (405mg, 99%)
I got Rf = 0.69 (toluene: ethyl acetate = 5: 3) ¹ H-NMR (CDCl ₃ ) δ: 7.43 to 7.20 (5H, m, Arom.H),
4.840 (1H, d, J = 11.7Hz, CH ₂ Ph), 4.742 (1H, d, J =
11.7Hz, CH ₂ Ph), 4.249 (1H, t, J = 6.2Hz, H-3), 4.190
(1H, dd, J = 2.2, 5.5Hz, H-4), 3.928 (1H, ddd, J
= 2.2, 5.8, 6.6Hz, H-5), 3.467 (1H, dd, J = 6.6, 9.6
Hz, H-2), 2.190 (3H, s, SMe), 2.082 (3H, s, OAc), 1.
445, 1.352 (6H, 2S, 2Me)

Example 3 Compound 6 (1.02 g, 2.13 mmol)
Dissolve in dichloromethane (10 mL), 75% trifluoroacetic acid
(1 mL) and stirred at 0 ° C. to room temperature for 2 hours. 75% trifluoroacetic acid (1 mL) was added, and the mixture was further stirred at room temperature for 15 hours. To the reaction solution was added a saturated aqueous solution of sodium bicarbonate, extracted with chloroform, washed with saturated saline, and dried over magnesium sulfate. The solvent was distilled off, the residue was dissolved in pyridine (2 mL), acetic anhydride (2 mL) and a catalytic amount of 4-dimethylaminopyridine were added, and the mixture was stirred at room temperature for 12 hours. The mixture was neutralized with 2N hydrochloric acid under ice-cooling, extracted with chloroform, washed with brine, and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (toluene: ethyl acetate = 5: 1) to obtain Compound 7 (505 mg, 50%). Rf = 0.31 (toluene: ethyl acetate = 10: 1) ¹ H NMR (CDCl ₃ ) δ: 2.064 (3H, s, Ac), 2.152 (3
H, s, Ac), 2.232 (3H, s, SMe), 3.785 (1H, br
-t, J = 6.0Hz, H-2), 4.141 (1H, s, H-6), 4.1
55 (1H, s, H-6 '), 4.384 (1H, d, J = 9.0Hz, H
-1), 4.514 (1H, d, J = 11.0Hz, CH ₂ Ph), 4.760
(1H, d, J = 11.5Hz, CH ₂ Ph), 4.780 (1H, d, 1
0.0Hz, CH ₂ Ph), 4.806 (1H, d, 10.0Hz, CH ₂ Ph),
5.550 (1H, d, 1.5Hz, H-4), 7.2-7.4 (10H, m,
Arom.H)

Example 4 Compound 8t (170 mg, 0.30 mmo
l), compound 5 (150 mg, 0.39 mmol) and molecular sieve 4A (1.5 g) were suspended in dichloromethane (3.0 mL), stirred at room temperature under a stream of argon gas, cooled to 0 ° C, and methyltriflate (68 μl, 0.6 mmol) and stirred for 1 hour. The reaction solution was neutralized by adding triethylamine, diluted with ethyl acetate, filtered through celite, and washed sequentially with saturated aqueous sodium hydrogen carbonate and saturated brine. After the ethyl acetate layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (15: 1 toluene: ethyl acetate).
Compound 9α (171 mg, 63%) and compound 9β (87 mg, 32%) were obtained. Compound 8t : Y.ito, 7,359 (1988) Compound 9α Rf = 0.72 (toluene: ethyl acetate = 10:
1) ¹ H-NMR (CDCl ₃ ) δ: 5.402 (1H, dd, J = 8.4, 15.4 Hz,
4Cer), 5.116 (1H, dt, J = 8.4, 15.0Hz, 5Cer), 4.7
71 (1H, d, J = 3.3Hz, H-1), 4.714 (1H, d, J = 12.5H
z, CH ₂ Ph), 4.675 (1H, d, J = 12.8Hz, CH ₂ Ph), 2.005
(3H, s, Ac), 1.368, 1.314 (6H, 2s, CH ₃ ), 1.060 (9
H, s, t -Bu), 0.882 (3H, t, J = 6.6 Hz, CH ₃ ). Compound 9β Rf = 0.48 (toluene-AcOEt = 10: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.401 ( 1H, dd, J = 8.1, 15.4Hz,
4Cer), 5.156 (1H, dt, J = 7.7, 15.4Hz, 5Cer), 4.6
20 (2H, s, CH ₂ Ph), 4.164 (1H, d, J = 8.1Hz, H-1),
2.057 (3H, s, Ac), 1.327, 1.310 (6H, 2s, CH ₃ ), 1.0
63 (9H, s, t -Bu), 0.881 (3H, t, J = 6.6Hz, CH ₃ ).

Example 5 Compound 9a (168 mg, 0.19 mmol) was dissolved in toluene (6 mL) and water (3 mL), triphenylphosphine (99 mg, 0.38 mmol) was added, and the mixture was refluxed for 19 hours. The solvent was distilled off, and the residue was separated with Sephadex LH-20 (1: 1 methanol-
Column purification was performed using chloroform, and the amino compound (163
mg, 99%). Then, the amino compound (110 mg, 0.13
mmol) in 1,2-dichloroethane (3 mL), lignoceric acid (163 mg, 0.44 mmol), 2-chloro-1-methylpyridinium iodide (108 mg, 0.42 mmol), tri-n-butylamine ( 191 μL, 0.88 mmol) and stirred at room temperature for 1 hour.
After diluting the reaction solution with chloroform, it was washed successively with saturated aqueous sodium hydrogen carbonate and saturated saline. After the chloroform layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (5: 1 toluene: ethyl acetate) to obtain Compound 10 (121 mg, 78%). Rf = 0.51 (toluene: ethyl acetate = 5: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.550 (1H, d, J = 9.2 Hz, NH), 5.
361 (1H, dd, J = 7.7, 15.4Hz, 4Cer), 5.191 (1H, d
t, J = 7.7, 15.0Hz, 5Cer), 4.761 (1H, d, J = 3.3Hz,
H-1), 4.658 (1H, d, J = 12.5Hz, CH ₂ Ph), 4.576 (1
H, d, J = 12.5Hz, CH ₂ Ph), 2.028 (3H, s, Ac), 1.37
9, 1.314 (6H, 2s, 2CH ₃ ), 1.046 (9H, s, t -Bu), 0.881
(6H, t, J = 7.0Hz , 2CH 3).

Example 6 Compound 10 (60 mg, 49 μmol) was added to 1
: 1 Methanol: Dissolve in tetrahydrofuran (0.6 mL), add 1N aqueous sodium hydroxide solution (0.3 mL) and add 1
After stirring for one day, the reaction solution was directly applied to Sephadex LH-20 (1: 2
Column purification with chloroform: methanol)
Compound 11 (51 mg, 89%) was obtained. Rf = 0.32 (toluene: ethyl acetate = 4: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.544 (1H, d, J = 9.2 Hz, NH), 5.
365 (1H, dd, J = 7.0, 15.4Hz, 4Cer), 5.280 (1H, d
t, J 6.6, 15,7Hz, 5Cer), 4.785 (1H, d, J = 3.7Hz, H
-1), 4.713 (1H, d, J = 12.1Hz, CH ₂ Ph), 4.614 (1H,
d, J = 12.5Hz, CH ₂ Ph), 1.377, 1.324 (6H, 2s, CH ₃ ),
1.046 (9H, s, t -Bu), 0.880 (6H, t, J = 6.6Hz, 2C
H ₃ ).

Example 7 Compound 10 (60 mg, 49 μmol)
It was dissolved in 1,2-dichloroethane (3 mL), and 75% trifluoroacetic acid (0.5 mL) was added, followed by stirring at room temperature for 1 hour. The solvent was distilled off, and the residue was purified by silica gel column chromatography (3: 2 toluene: ethyl acetate) to give Compound 12 (10 mg, 1 mg).
7%) and compound 13 (34 mg, 73%). Compound 12 Rf = 0.12 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 6.298 (1H, d, J = 8.1 Hz, NH), 5.
705 (1H, dt, J = 7.4, 15.4Hz, 5Cer), 5.457 (1H, d
d, J = 5.5, 15.4Hz, 4Cer), 4.849 (1H, d, J = 3.7Hz,
H-1), 4.731 (1H, d, J = 11.7Hz, CH ₂ Ph), 4.654 (1
H, d, J = 11.7Hz, CH ₂ Ph), 2.082 (3H, s, Ac), 0.880
(6H, t, J = 7.0 Hz, 2CH ₃ ). Compound 13 Rf = 0.31 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.563 (1H, d, J = 8.8 Hz, NH), 5.
377 (1H, dd, J = 7.3, 15.4Hz, 4Cer), 5.268 (1H, d
t, J = 7.0, 15.4Hz, 5Cer), 4.821 (1H, d, J = 3.3Hz,
H-1), 4.56-4.51 (2H, 2br-d, CH ₂ Ph), 2.033 (3H, s,
Ac), 1.051 (9H, s, t -Bu), 0.881 (6H, t, J = 6.6H
z, 2CH ₃ ).

Example 8 Compound 13 (34 mg, 36 μmol),
Fucose donor 14 (14 mg, 46 μmol) and molecular sieve 4A (500 mg) were suspended in dichloromethane (2.0 mL),
After stirring at room temperature under a stream of argon gas, the mixture was cooled to -15 ° C, dibutyltin dichloride (28 mg, 93 μmol) and silver triflate (48 mg, 0.19 mmol) were added, and the mixture was stirred for 4.5 hours. The reaction solution was neutralized by adding triethylamine, diluted with ethyl acetate, filtered through celite, and washed sequentially with saturated aqueous sodium hydrogen carbonate and saturated brine. After drying the ethyl acetate layer with magnesium sulfate,
The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (4: 1 toluene: ethyl acetate).
Compound 15 (19 mg, 43%) and trisaccharide derivative 16 (15 mg, 29%) were obtained. Compound 15 Rf = 0.30 (toluene: ethyl acetate = 3: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.38-7.30 (5H, m, Arom.H), 5.754
(1H, d, J = 8.6Hz, NH), 5.678 (1H, dt, J = 8.0, 1
5.4Hz, 5Cer), 5.506 (1H, dd, J = 8.4, 15.4Hz, 4Ce
r), 5.160 (1H, dd, J = 8.1, 10.5Hz, H-2b), 5.141
(1H, d, J = 3.0Hz, H-4b), 4.947 (1H, d, J = 3.3Hz,
H-1a), 4.698 (1H, d, J = 12.0Hz, CH ₂ Ph), 4.643 (1
H, d, J = 12.0Hz, CH ₂ Ph), 4.391 (1H, d, J = 8.3Hz,
H-1b), 2.161, 2.085, 2.020, 1.981 (12H, 4s, 4Ac),
1.120 (3H, d, J = 6.5Hz, H-6b), 0.880 (6H, t, J =
. 7.0Hz, 2CH ₃₎ Compound 16 Rf = 0.52 (toluene: ethyl acetate ^{= 3: 1) 1 H-} NMR (CDCl 3) δ: 7.43-7.29 (5H, m, Arom.H), 5.863
(1H, d, J = 9.2Hz, NH), 5.596 (1H, dt, J = 8.0, 1
5.4Hz, 5Cer), 5.462 (1H, dd, J = 8.3, 15.4Hz, 4Ce
r), 5.256 (1H, dd, J = 8.1, 10.5Hz, H-2b or H-2c),
5.230 (1H, d, J = 3.3Hz, H-4b or H-4c), 5.144 (1H,
dd, J = 8.1, 10.3Hz, H-2b or H-2c), 5.085 (1H, d,
J = 3.3Hz, H-4b or H-4c), 5.033 (1H, dd, J = 3.3,
10.6Hz, H-3b or H-3c), 4.916 (1H, d, J = 3.3Hz, H-1
a), 4.904 (1H, dd, J = 3.7,10.6Hz, H-3b or H-3c),
4.837 (1H, d, J = 11.7Hz, CH ₂ Ph), 4.724 (1H, d, J =
8.1Hz, H-1b or H-1c), 4.637 (1H, d, J = 11.4Hz, C
H ₂ Ph), 4.364 (1H, d, J = 8.1Hz, H-1b or H-1c), 1.20
2 (3H, d, J = 6.6Hz, H-6b or H-6c), 1.155 (3H, d, J
= 6.6Hz, H-6b or H-6c), 0.880 (6H, t, J = 7.0Hz,
2CH ₃ ).

Example 9 Compound 15 (19 mg, 15 μmol) was dissolved in pyridine (3 mL), acetic anhydride (2 mL) and a catalytic amount of dimethylaminopyridine were added, and the mixture was stirred at room temperature for 1 day. After azeotropic distillation with toluene, the residue was purified by silica gel column chromatography (7: 1 toluene: acetone) to obtain Compound 17 (19 mg, 96%). Rf = 0.58 (toluene: acetone = 4: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.38-7.30 (5H, m, Arom.H), 5.659
(1H, d, J = 8.8Hz, NH), 5.627 (1H, dt, J = 8.0, 1
5.4Hz, 5Cer), 5.498 (1H, dd, J = 8.4, 15.4Hz, 4Ce
r), 5.428 (1H, d, J = 2.6Hz, H-4b), 5.331 (1H, dd,
J = 3.3, 10.3Hz, H-3b), 5.139 (1H, dd, J = 8.1, 1
0.3Hz, H-2b), 5.045 (1H, d, J = 3.0Hz, H-4a), 5.00
3 (1H, d, J = 3.3Hz, H-1a), 4.72-4.67 (2H, 2br-d,
CH ₂ Ph), 4.396 (1H, d, J = 8.1Hz, H-1b), 3.896 (1H,
dd, J = 3.3, 10.6Hz, H-2a), 2.145, 2.126, 2.044,
2.024, 1.988, 1.975 (18H, 6s, 6Ac), 1.052 (3H, d,
J = 6.2Hz, H-6b) , 0.880 (6H, t, J = 7.0Hz, 2CH 3).

Example 10 Compound 17 (19 mg, 15 μmol)
4: 1 = Dissolve in methanol: water (8 mL), add 20% palladium hydroxide-carbon (19 mg), replace with hydrogen gas, and
The catalytic reduction was performed for 19 hours. The reaction solution was filtered through celite, and the filtrate was distilled off. The residue was subjected to silica gel column chromatography (5:
Purification using 1 toluene: acetone) gave compound 18 (1
7 mg, 99%). Rf = 0.35 (toluene: acetone = 4: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.946 (1H, d, J = 8.8Hz, NH), 5.
414 (1H, d, J = 2.2Hz, H-4b), 5.211 (1H, d, J = 3.
3Hz, H-4a), 5.138 (1H, dd, J = 8.1, 10.3Hz, H-2b),
5.085 (1H, dd, J = 3.3, 10.6Hz, H-3b), 4.937 (1H,
d, J = 4.0Hz, H-1a), 4.546 (1H, d, J = 7.7Hz, H-1
b), 2.182, 2.130, 2.082, 2.052, 2.050, 1.988 (18H,
6s, 6Ac), 1.194 (3H, d, J = 6.2Hz, H-6b), 0.880
(6H, t, J = 7.0Hz, 2CH ₃ ).

Example 11 Compound 18 (17 mg, 15 μmol) was added to 1
: 1 Methanol: Dissolve in tetrahydrofuran (0.6 mL), add 1N aqueous sodium hydroxide solution (0.3 mL) and add 1
After stirring for one day, the reaction solution was directly subjected to column purification using Sephadex LH-20 (chloroform: methanol = 2: 1) to obtain Compound 19 (14 mg, 99%). Rf = 0.71 (chloroform: methanol = 2: 1) ¹ H-NMR (CD ₃ OD-CDCl ₃ ) δ: 4.886 (1H, d, J = 3.7 Hz, H
-1a), 4.314 (1H, br-d, J = 7.7Hz, H-1b), 0.894 (6
H, t, J = 7.0Hz, 2CH ₃ ).

Example 12 Compound 16 (15 mg, 10 μmol)
4: 1 = Dissolve in methanol: water (8 mL), add 20% palladium hydroxide-carbon (15 mg), replace with hydrogen gas, and
The catalytic reduction was performed for 19 hours. The reaction solution was filtered through celite, and the filtrate was distilled off. The residue was purified by silica gel column chromatography (3:
Purification using 1 toluene: acetone) gave compound 20 (1
0 mg, 70%). Rf = 0.24 (toluene: acetone = 3: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.875 (1H, d, J = 8.8Hz, NH), 5.
268 (1H, d, J = 2.6Hz, H-4b or H-4c), 5.214 (1H, d
d, J = 8.1, 10.6Hz, H-2b or H-2c), 5.208 (1H, d, J
= 3.7Hz, H-4b or H-4c), 5.136 (1H, dd, J = 8.1, 1
0.3Hz, H-2b orH-2c), 5.051 (1H, dd, J = 3.7, 10.3H
z, H-3b or H-3c), 4.998 (1H, dd, J = 3.7, 10.3Hz, H
-3b or H-3c), 4.934 (1H, d, J = 3.7Hz, H-1a), 4.59
6 (1H, d, J = 8.1Hz, H-1b or H-1c), 4.589 (1H, d, J
= 8.1Hz, H-1b or H-1c), 2.197, 2.181, 2.093, 2.08
6, 2.076, 2.005, 1.981 (21H, 7s, 7Ac), 1.232 (3H,
d, J = 6.7Hz, H-6b or H-6c), 1.169 (3H, d, J = 6.2
Hz, H-6b or H-6c), 0.880 (6H, t, J = 7.0Hz, 2CH ₃ ).

Example 13 Compound 20 (10 mg, 7.1 μmol)
Dissolve in 1: 1 methanol: tetrahydrofuran (0.6 mL), add 1N-aqueous sodium hydroxide solution (0.3 mL), stir at room temperature for 1 day, then directly react the reaction solution with Sephadex LH-20 (chloroform: methanol = 2: 1 ) To give Compound 21 (6.0 mg, 76%). Rf = 0.66 (chloroform: methanol = 2: 1) ¹ H-NMR (CD ₃ OD-CDCl ₃ ) δ: 4.958 (1H, d, J = 2.6 Hz, H
-1a), 4.362 (1H, d, J = 7.3Hz, H-1c), 4.343 (1H, d,
J = 8.1Hz, H-1b) , 0.894 (6H, t, J = 7.3Hz, 2CH 3).

<Example 14> Rhamnose donor 23 (235 mg,
0.73 mmol), galactose receptor 22 (245 mg, 0.61 mmol),
Molecular sieves 4A (1g), 1,2-dichloroethane (4m
L) under stirring at room temperature, methyl triflate (208m
L, 1.84 mmol) and stirred for 15 hours. The reaction solution was neutralized with triethylamine, diluted with chloroform, and filtered through celite. The filtrate was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, and the organic layer was dried over magnesium sulfate. The solvent was distilled off, and pyridine (15 mL), acetic anhydride (15 mL) and a catalytic amount of 4-dimethylaminopyridine were added to the residue, and the mixture was stirred at room temperature overnight. The residue obtained by azeotropic distillation of the reaction solution with toluene was purified by silica gel column (toluene: ethyl acetate = 5: 2) to give compound 24.
And a 5: 2 mixture of Compound 25 (290 mg, 66%). And the trisaccharide derivative 26 (51 mg, 9%) was obtained. Compound 23 : Andras Liptak, J. carbohydr. Chem., 7
(3), 1988, 687-699. Compound 24 and Compound 25 (5: 2 mixture) Rf = 0.60 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.39 to 7.17 (10H, m, Arom. H),
5.933 (1H, m, -OCH ₂ C H = CH ₂ ), 5.384 (0.72H, d, J = 3.
3Hz, H-4b ( 24 )), 4.964 (0.28H, dd, J = 3.3, 10.3Hz, H
-3b ( 25 )), 2.163, 2.068, 2.062, 1.963 (8.6H, 4S, 4A
c ( 24 )), 2.135, 2.043, 2.005, 1.979 (3.4H, 4S, 4Ac ( 2
5 )), 1.204 (2.1H, d, J = 6.2Hz, H-6b ( 24 )), 1.127
(0.9H, d, J = 6.2Hz, H-6b ( 25 )) Compound 26 Rf = 0.43 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 7.39 to 7.20 (10H, m , Arom. H),
5.930 (1H, m, -OCH ₂ C H = CH ₂ ), 5.383 (1H, dd, J = 3.3,
9.9Hz, H-3b or H-3c), 5.162 (1H, dd, J = 3.3, 9.9H
z, H-3c or H-3b), 5.108 (1H, t, J = 9.9Hz, H-4b or H
-4c), 4.998 (1H, t, J = 9.9Hz, H-4c or H-4b), 4.93
2 (1H, d, J = 10.6Hz, CH ₂ Ph), 4.652 (1H, d, J = 10.6H
z, CH ₂ Ph), 4.633 (1H, d, J = 11.7Hz, CH ₂ Ph), 4.536 (1
H, d, J = 11.7Hz, CH ₂ Ph), 4.413 (1H, d, J = 7.0Hz, H
-1a), 4.053 (1H, m, H-5b or H-5c), 3.975 (1H, m, H-5
c or H-5b), 2.183, 2.037, 2.024, 2.016, 2.003, 1.9
30 (18H, 6S, 6Ac), 1.188 (1H, d, J = 6.6Hz, H-6b or
H-6c), 1.089 (1H, d, J = 6.2Hz, H-6c or H-6b)

Example 15 Compoundtwenty fourWhentwenty fiveMixture (1.33g,
 1.86 mmol) in tetrahydrofuran (10 mL)
Iridium complex activated with elemental gas (90mg, 0.076mmo
l) in tetrahydrofuran (10 mL)
After stirring, add iodine (0.95 g, 3.74 mmol) and water (3 mL)
The mixture was further stirred at room temperature for 30 minutes. The reaction solution was chloroform (10
0 mL), 10% potassium iodide solution, saturated sodium bicarbonate
After washing sequentially with water and saturated saline, the organic layer was washed with magnesium sulfate.
Dried. Crude hemiacetal obtained by removing the solvent
Pyridine (20 mL), acetic anhydride (20 mL), catalytic amount of 4-diamine
Methylaminopyridine was added and the mixture was stirred at room temperature overnight. solvent
Is azeotroped with toluene, and the residue is separated on a silica gel column (tolue).
: Ethyl acetate = 4: 1) Purified pentaacetate
(1.22 g, 82%). This Pentaacete
(1.22 g, 1.70 mmol), 20% palladium hydroxide
Mixture of carbon (0.7g), methanol (32mL), water (8mL)
Was catalytically reduced at room temperature. The catalyst was filtered through celite, and the filtrate was filtered.
Pyridine (30 mL) was added to the residue obtained by azeotropic distillation with toluene, and anhydrous
Acetic acid (30 mL) and a catalytic amount of 4-dimethylaminopyridine
The mixture was stirred overnight at room temperature. The solvent is azeotroped with toluene,
The residue is subjected to a silica gel column (toluene: ethyl acetate = 1:
1) Purify the compound27(657mg, 62%), compound28
(142 mg, 13%). Compound27 Rf = 0.41 (toluene: ethyl acetate = 1: 1)¹ H-NMR (CDCl_Three) δ: 6.376 (0.5H, d, J = 3.7Hz, H-1
aα), 5.618 (0.5H, d, J = 8.4Hz, H-1aβ), 5.478 (0.5
H, d, J = 2.2Hz, H-4aα or H-4aβ), 5.405 (0.5H,
d, J = 2.2Hz, H-4aβ or H-4aα), 1.252 (1.5H, d, J
 = 6.2Hz, H-6bα or H-6bβ), 1.223 (1.5H, d, J =
6.2Hz, H-6bβ or H-6bα) compound28 Rf = 0.34 (toluene: ethyl acetate = 1: 1)¹ H-NMR (CDCl_Three) δ: 6.398 (0.5H, d, J = 3.7Hz, H-1
aα), 5.702 (0.5H, d, J = 8.4Hz, H-1aβ), 4.827 (0.5
H, d, J = 1.8Hz, H-1bβ or H-1bα), 4.798 (0.5H, d,
 J = 1.8Hz, H-1bα or H-1bβ), 1.218 (1.5H, d, J =
6.2Hz, H-6bβor H-6bα), 1.210 (1.5H, d, J = 6.2H
z, H-6bα or H-6bβ)

Example 16 Compound 27 (642 mg, 1.03 mmol
l), a mixture of hydrazineacetic acid (190 mg, 2.06 mmol) and dimethylformamide (4 mL) was stirred at room temperature for 1.5 hours.
The reaction solution was purified by Sephadex LH-20 (methanol) to obtain a hemiacetal compound. Of this hemiacetal body
A 1,2-dichloroethane (4 mL) solution was stirred at -5 ° C while trichloroacetonitrile (1 mL, 10 mmol), 1,8-diazabicyclo [5.4.0] undec-7-ene (308 µL, 2.
06 mmol) and stirred overnight at room temperature. The reaction solution was purified by a silica gel column (toluene: ethyl acetate = 4: 1 to 2: 1) to obtain Compound 29 (468 mg, 63%). Rf = 0.41 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 8.662 (1H, s, = NH), 6.609 (1H,
d, J = 3.7Hz, H-1a), 5.527 (1H, d, J = 3.7Hz, H-4
a), 5.278 (1H, dd, J = 3.7, 10.3Hz, H-2a), 5.140 (1H,
dd, J = 3.3, 10.3Hz, H-3b), 5.094 (1H, t, J = 10.3H
z, H-4b), 5.064 (1H, dd, J = 1.8, 2.9Hz, H-2b), 5.
035 (1H, d, J = 1.8Hz, H-1b), 4.400 (1H, t, J = 5.9H
z, H-5b), 4.297 (1H, dd, J = 3.3, 10.3Hz, H-3a), 4.2
09 (1H, dd, J = 5.5, 11.7Hz, H-6a), 4.050 (1H, dd, J =
7.0, 11.7Hz, H-6a '), 2.238, 2.135, 2.080, 2.065,
2.038, 1.994 (18H, 6s, 6Ac), 1.258 (3H, d, J = 6.2H
z, H-6b)

Example 17 Compound 28 (130 mg, 0.21 mmol
l), a mixture of hydrazineacetic acid (39 mg, 0.42 mmol) and dimethylformamide (1 mL) was stirred at room temperature for 1.5 hours. The reaction solution was purified by Sephadex LH-20 (methanol) to obtain a hemiacetal compound. Of this hemiacetal body
The 1,2-dichloroethane (4 mL) solution was stirred at -5 ° C. while trichloroacetonitrile (210 mL, 2.1 mmol), 1,8-diazabicyclo [5.4.0] undecouene (308 μL, 0.1 mL).
42 mmol) and stirred overnight at room temperature. The reaction solution was purified by a silica gel column (toluene: ethyl acetate = 4: 1 to 2: 1) to obtain Compound 30 (55 mg, 36%). Rf = 0.58 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 8.667 (1H, s, = NH), 6.635 (1H,
d, J = 3.7Hz, H-1a), 5.341 (1H, dd, J = 3.3, 9.9Hz, H
-3b), 5.101 (1H, t, J = 9.9Hz, H-4b), 4.805 (1H, d,
J = 2.2Hz, H-1b), 4.338 (1H, t, J = 6.2Hz, H-5a), 4.
264 (1H, br-s, H-4a), 4.216 (1H, dd, J = 6.6, 11.0Hz,
H-6a), 4.152 (1H, dd, J = 6.6, 11.0Hz, H-6a '), 2.15
3, 2.137, 2.075, 2.048, 2.028, 2.017 (18H, 6s, 6A
c), 1.221 (3H, d, J = 6.2Hz, H-6b)

Example 18 Compound 29 (250 mg, 346 μmol) and Compound 8t (130 mg, 230 μmol) were dissolved in dichloromethane (2 mL), and the mixture was stirred with Molecular Sieve 4A (500 mg) under a stream of argon gas. After cooling to 15 ° C., t -butyldimethylsilyl triflate (27 mL, 230 mmol) was added and the mixture was stirred for 30 minutes. The reaction solution was neutralized by adding triethylamine, diluted with chloroform, filtered through celite, and washed sequentially with saturated aqueous sodium hydrogen carbonate and saturated saline. After the chloroform layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by a silica gel column (3: 1 toluene: ethyl acetate) to obtain Compound 31 (35 mg, 14%). Rf = 0.56 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.200 (1H, dd, J = 8.1, 9.9Hz, H
-2a), 4.973 (1H, dd, J = 1.8, 3.3Hz, H-2b), 4.886
(1H, br-s, H-1b), 4.287 (1H, d, J = 8.1Hz, H-1a),
2.222, 2.130, 2.066, 2.053, 1.992, 1.944 (18H, 6s,
6Ac), 1.052 (9H, s, t -Bu), 0.883 (3H, t, J = 7.0H
z, CH ₃ ).

Example 19 Compound 31 (35 mg, 31 μmol) was dissolved in toluene (3 mL) and water (1 mL), triphenylphosphine (17 mg, 63 μmol) was added, and the mixture was refluxed for 19 hours. The residue was purified by column using Sephadex LH-20 (2: 1 methanol: chloroform), and the amino compound (35 m
g, 99%). Then, the amino compound (35 mg, 31 μmo
l) in 1,2-dichloroethane (1 mL) and lignoceric acid (39 mg, 110 μmol), 2-chloro-1-methylpyridinium iodide (27 mg, 110 μmol), tri- n -butylamine (4
(8 mL, 220 μmol) and stirred at room temperature for 1 hour. After diluting the reaction solution with chloroform, it was washed successively with saturated aqueous sodium hydrogen carbonate and saturated saline. After the chloroform layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue is Sephadex LH-2
0 (2: 1 chloroform: methanol) column purification,
Purification was performed sequentially on a silica gel column (2: 1 toluene: ethyl acetate) to give Compound 32 (23 mg, 50%). Rf = 0.40 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.509 (1H, d, J = 8.4 Hz, NH), 5.
385 (1H, d, J = 3.3Hz, H-4a), 5.186 (1H, dd, J =
7.7, 9.9Hz, H-2a), 5.004 (1H, br-dd, H-2b), 4.939
(1H, s, H-1b), 4.363 (1H, d, J = 8.1Hz, H-1a), 2.2
58, 2.134, 2.075, 2.066, 2.036, 1.997 (18H, 6s, 6A
c), 1.005 (9H, s, t -Bu), 0.881 (6H, t, J = 7.0Hz,
2CH ₃ ).

Example 20 Compound 32 (23 mg, 16 μmol)
1: 1 Dissolve in methanol: tetrahydrofuran (1 mL), add 1N aqueous sodium hydroxide solution (0.3 mL), and add
Stirred for days. The reaction solution was directly added to Sephadex LH-20 (1:
Column purification was performed using 2 chloroform: methanol) to obtain Compound 33 (16 mg, 99%). Compound 33 (16 mg,
16 μmol) in tetrahydrofuran (1 mL) and 1N-
After adding a tetrabutylammonium fluoride / tetrahydrofuran solution (550 μL) and stirring at 60 ° C. for 14 hours, the solvent was distilled off, and the residue was subjected to column purification using Sephadex LH-20 (2: 1 chloroform: methanol) to give Compound 34. (1
5 mg, 99%). Rf = 0.46 (chloroform: methanol = 5: 1) ¹ H-NMR data (CD ₃ OD-CDCl ₃ ) δ: 5.713 (1H, dt, J =
7.0, 15.4Hz, 5Cer), 5.474 (1H, dd, J = 7.3, 15.4Hz,
4Cer), 5.093 (1H, br-s, H-1b), 4.263 (1H, d, J =
7.7Hz, H-1a), 0.895 (6H, t, J = 7.3Hz, 2CH 3).

Example 21 Compound 7 (303 mg, 638 μmol),
Compound 8c (325 mg, 575 μmol) was added to dichloromethane (7 m
L), and methyl triflate (44 μL, 633 μmol)
Was added and stirred at 0 ° C. to room temperature overnight in the presence of MS4A (1 g). After neutralization with triethylamine, MS4A was filtered off and diluted with chloroform. The extract was washed successively with a saturated aqueous solution of sodium bicarbonate and saturated saline, and dried over magnesium sulfate. The solvent is distilled off, and the residue is subjected to silica gel column chromatography (toluene:
Purified with ethyl acetate = 20: 1) to give compound 35α (423 mg, 74
%) And compound 35β (59 mg, 10%) were obtained. Compound 35α Rf = 0.31 (toluene: ethyl acetate = 20:
1) ¹ H NMR (CDCl ₃ ) δ: 5.527 (1H, d, 3.3 Hz, H-4),
5.412 (1H, dd, 9.5, 10.5Hz, H-4Cer), 5.29 (1H
, m, H-5Cer), 4.877 (1H, d, 3.5Hz, H-1), 3.
772 (1H, dd, 3.7, 10.3Hz, H-2), 3.392 (1H, d
d, 3.3, 9.9Hz, H-3), 2.017 (3H, s, Ac), 2.0
07 (3H, s, Ac) , 0.880 (3H, t, 6.8Hz, C 12 H 24
Me ) Compound 35β Rf = 0.26 (toluene: ethyl acetate = 20:
1) ¹ H NMR (CDCl ₃ ) δ: 5.490 (1H, d, 2.2 Hz, H-4),
5.405 (1H, dd, 9.5, 10.5Hz, H-4Cer), 5.30 (1H
, m, H-5Cer), 2.319 (1H, d, 7.5Hz, H-1), 2.1
54 (3H, s, Ac), 2.061 (3H, s, Ac), 0.880 (3
_{H, t, 6.9Hz, C 12} H 24 Me)

Example 22 Compound 35α (249 mg, 251 μmo
l) in tetrahydrofuran: methanol (1: 1) mixed solvent
(10mL) and 1N-sodium hydroxide aqueous solution (1mL)
Was added and stirred at room temperature overnight. After evaporating the solvent, silica gel column chromatography (toluene: ethyl acetate = 3:
Purification by 1) yielded compound 36 (184 mg, 81%). Rf = 0.33 (toluene: ethyl acetate = 3: 1) ¹ H NMR (CDCl ₃ ) δ: 5.410 (1H, dd, 9.5, 11.0 Hz,
H-4Cer), 5.29 (1H, m, H-5Cer), 4.879 (1H, d
, 2.9Hz, H-1), 4.511 (1H, dd, 4.5, 9.0Hz, H
-3Cer), 4.062 (1H, br.s, H-4), 0.880 (3H, t,
7.0Hz, C ₁₂ H ₂₄ Me)

Example 23 Compound 35β (91 mg, 92 μmol)
To tetrahydrofuran: methanol (1: 1) mixed solvent
(5 mL), 1N-aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at room temperature overnight. After evaporating the solvent, silica gel column chromatography (toluene: ethyl acetate = 3: 1)
The compound 37 (76 mg, 92%) was obtained. Rf = 0.19 (toluene: ethyl acetate = 5: 1) ¹ H NMR (CDCl ₃ ) δ: 5.408 (1H, br-d, 10.1 Hz, H-
4Cer), 5.31 (1H, m, H-5Cer), 4.780 (1H, d, 11.
0Hz, CH ₂ Ph), 4.718 (1H, d, 12.0Hz, CH ₂ Ph), 4.
690 (1H, d, 12.0Hz, CH ₂ Ph), 4.633 (1H, d, J
= 11.0Hz, CH ₂ Ph), 4.288 (1H, d, J = 7.7Hz, H-
1), 3.978 (1H, d, J = 2.6Hz, H-4), 0.880 (3H,
_{t, J = 7.0Hz, C 12} H 24 Me), 3.978 (1H, d, J = 2.
6Hz, H-4)

Example 24 Compound 35α (163 mg, 164 μmo
l) was suspended in a mixed solvent of toluene (15 mL) and water (5 mL),
Add triphenylphosphine (86 mg, 328 μmol) and add 18
Heated to reflux for an hour. After the solvent was distilled off, the residue was subjected to silica gel column chromatography (toluene: ethyl acetate =
3: 1) to give compound 38 (149 mg, 94%). Rf = 0.44 (toluene: ethyl acetate = 4: 1) ¹ H NMR (CDCl ₃ ) δ: 5.542 (1H, d, J = 3.3 Hz, H-
4), 5.395 (1H, br-t, J = 10.3Hz, H-4Cer), 5.27
(1H, m, H-5Cer), 4.884 (1H, d, J = 3.7Hz, H
-1), 2.112 (3H, s, Ac), 2.014 (3H, s, Ac),
0.880 (3H, t, J = 6.7Hz, C 12 H 24 Me)

Example 25 Compound 38 (73 mg, 76 μmol) was added to 1,
Dissolve in 2-dichloroethane (2 mL) and lignoceric acid (98
mg, 0.27 mmol), 2-chloro-1-methylpyridinium iodide (65 mg, 0.25 mmol), tri- n -butylamine (115 mL,
(0.53 mmol) and stirred at room temperature for 1 hour. After diluting the reaction solution with chloroform, it was washed successively with saturated aqueous sodium hydrogen carbonate and saturated saline. After drying the chloroform layer with magnesium sulfate,
The solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column (10: 1 toluene: ethyl acetate) to give Compound 39 (81 mg, 8
1%). Rf = 0.80 (toluene: ethyl acetate = 4: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.592 (1H, d, J = 9.5 Hz, NH), 5.
533 (1H, d, J = 3.3Hz, H-4), 5.348 (1H, br-dd, 4Ce
r), 5.226 (1H, br-dt, 5Cer), 4.860 (1H, d, J = 3.3H
z, H-1), 4.782 (1H, d, J = 11.7Hz, CH ₂ Ph), 4.712
(1H, d, J = 11.0Hz, CH ₂ Ph), 4.603 (1H, d, J = 11.1
Hz, CH ₂ Ph), 4.488 (1H, d, J = 11.4Hz, CH ₂ Ph), 2.10
3, 2.033 (6H, 2s, 2Ac), 1.047 (9H, s, t -Bu), 0.879
(9H, t, J = 7.0Hz, 2CH ₃ )

Example 26 Compound 39 (60 mg, 46 μmol)
1: 1 Methanol: Dissolved in tetrahydrofuran (1.5 mL), 1N-aqueous sodium hydroxide solution (0.5 mL) was added, and the mixture was stirred at room temperature for 1 day.The reaction solution was directly added to Sephadex LH-20 (1:
Column purification was performed using 2 chloroform: methanol) to obtain Compound 40 (8 mg, 88%). Rf = 0.70 (toluene: ethyl acetate = 2: 3) ¹ H-NMR (CDCl ₃ ) δ: 5.628 (1H, d, J = 8.8Hz, NH),
5.354 (1H, br-dd, 4Cer), 5.282 (1H, br-dt, 5Cer),
4.840 (1H, d, J = 3.7Hz, H-1), 4.780 (1H, d, J = 1
2.1Hz, CH ₂ Ph), 4.749 (1H, d, J = 11.4Hz, CH ₂ Ph),
4.664 (1H, d, J = 11.4Hz, CH ₂ Ph), 4.636 (1H, d, J =
12.1Hz, CH ₂ Ph), 1.048 (9H, s, t -Bu), 0.880 (9H, t,
J = 6.8Hz, 2CH ₃ )

Example 27 Compound 40 (35 mg, 28 μmol),
Fucose donor 41 (19 mg, 38 μmol) in dichloromethane
(2.0 mL), and the mixture was stirred at room temperature with a molecular sieve 4A (500 mg) under a stream of argon gas, cooled to 0 ° C., silver triflate (12 mg, 47 μmol) was added, and the mixture was stirred for 4 hours. The reaction solution was neutralized by adding triethylamine, diluted with ethyl acetate, filtered through celite, and washed sequentially with saturated aqueous sodium hydrogen carbonate and saturated brine. After the ethyl acetate layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (4: 1 toluene: ethyl acetate) to obtain Compound 42 (37 mg, 80%). Rf = 0.62 (toluene: ethyl acetate = 2: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.580 (1H, br-d, H-4b), 5.474 (1
H, dd, J = 3.3, 10.6Hz, H-3b), 5.232 (1H, m, 5Ce
r), 4.782 (1H, d, J = 2.9Hz, H-1a), 4.734 (1H, d,
J = 7.7Hz, H-1b), 4.679 (1H, d, J = 11.8Hz, CH ₂ P
h), 4.592-4.527 (3H, m, CH ₂ Ph), 1.045 (9H, s, t -B
u), 0.879 (9H, t, J = 7.0Hz, 2CH ₃ )

Example 28 Compound 42 (37 mg, 22 μmol)
4: 1 = Dissolve in methanol: water (6 mL), add 20% palladium hydroxide-carbon (37 mg), replace with hydrogen gas, and
The catalytic reduction was performed for 19 hours. The reaction solution was filtered through celite, and the filtrate was distilled off. The residue was dissolved in 1: 1 methanol: tetrahydrofuran (0.6 mL), 1N-aqueous sodium hydroxide solution (0.3 mL) was added, and the mixture was stirred at room temperature for 1 day. Then, the reaction solution was directly added to Sephadex LH-20 (1: 2 chloroform: Column purification was performed using methanol H) to obtain Compound 43 (25 mg, 96%). Compound 43 (25 mg, 21 μmol) in tetrahydrofuran
(1 mL), add 1N-tetrabutylammonium fluoride / tetrahydrofuran solution (1 mL), and add
After stirring for 4 hours, the solvent was distilled off, and the residue was separated with Sephadex LH-20.
Column purification was performed using (2: 1 CHCl ₃ -MeOH). continue,
Dissolve in pyridine (3 mL), add acetic anhydride (2 mL) and catalytic amount of dimethylaminopyridine, stir at room temperature for 1 day, azeotropically evaporate the reaction mixture with toluene, and elute the residue with silica gel column chromatography (20: 1 chloroform : Methanol) to obtain Compound 44 (19 mg, 73%). Compound 44 (19 mg, 15
μmol) in 1: 1 methanol: tetrahydrofuran (0.
6 mL), add 1N-aqueous sodium hydroxide solution (0.3 mL), stir at room temperature for 1 day, and directly transfer the reaction solution to Sephadex L
Column purification was performed using H-20 (1: 2 chloroform: methanol) to obtain Compound 45 (12 mg, 61%). Rf = 0.38 (chloroform: methanol = 25: 1) ¹ H-NMR (CD ₃ OD-CDCl ₃ ) δ: 4.841 (1H, d, J = 3.7 Hz, H
-1a), 4.239 (1H, d, J = 7.3Hz, H-1b), 0.896 (6H, t,
J = 6.7Hz, 2CH ₃ ).

Example 29 Compound 40 (15 mg, 12 μmol),
Galactose donor 46 (12 mg, 16 μmol) was dissolved in dichloromethane (2.5 mL) and molecular sieve 4A (500 mg) was stirred at room temperature under an argon gas stream at room temperature, cooled to 0 ° C, and silver triflate (6.3 mg, 25 μmol), and
Stir for 4 hours. The reaction solution was neutralized by adding triethylamine, diluted with ethyl acetate, filtered through celite, and saturated aqueous sodium hydrogen carbonate.
Washed sequentially with saturated saline. After the ethyl acetate layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure. Silica gel column chromatography of the residue (6: 1 toluene: ethyl acetate)
Was performed to obtain Compound 47 (15 mg, 70%). Rf = 0.64 (toluene: ethyl acetate = 4: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.957 (1H, d, J = 2.9 Hz, H-4b),
5.761 (1H, dd, J = 8.1, 10.3Hz, H-2b), 5.593 (1H,
dd, J = 3.3, 10.3Hz, H-3b), 4.967 (1H, d, J = 8.1H
z, H-1b), 4.662 (1H, d, J = 3.3Hz, H-1a), 3.941 (1
H, br-s, H-4a), 3.760 (1H, dd, J = 3.7, 10.9Hz, H-
3a), 3.630 (1H, dd, J = 3.3, 9.9Hz, H-2a), 2.412,
2.378, 2.291, 2.260 (12H, 4s, 4CH ₃ ), 1.059 (9H, s,
t -Bu), 0.878 (6H, t, J = 7.0Hz, 2CH ₃ ).

Example 30 Compound 47 (15 mg, 8.4 μmol)
4: 1 = Dissolved in methanol: water (10 mL), added with 20% palladium hydroxide-carbon (15 mg), replaced with hydrogen gas and subjected to catalytic reduction at room temperature for 6 hours. The reaction solution was filtered through celite,
The filtrate was distilled off. The residue was dissolved in 1: 1 methanol: tetrahydrofuran (0.6 mL), 1N-sodium hydroxide solution (0.3 mL) was added, the mixture was stirred at room temperature for 1 day, and the reaction solution was directly added to Sephadex LH-20 (1: 2 chloroform: Purification by column with methanol) gave Compound 48 (11 mg, qu.).
Compound 48 (11 mg, 8.4 μmol) was added to tetrahydrofuran (1
1N-tetrabutylammonium fluoride / tetrahydrofuran solution (1 mL) and added at 60 ° C.
After stirring for an hour, the solvent was distilled off, and the residue was separated with Sephadex LH-20.
Column purification was performed using (2: 1 chloroform-methanol). Subsequently, it was dissolved in pyridine (3 mL) and acetic anhydride (2 m
L), a catalytic amount of dimethylaminopyridine was added, the mixture was stirred at room temperature for 1 day, the reaction solution was azeotropically distilled with toluene, and the residue was purified by Sephadex LH-20 (1: 2 CHCl ₃ -MeOH) to obtain a compound. 49 (7 mg, 63%) was obtained. Compound 49 (7 mg, 5.3 μmol)
After dissolving in 1: 1 methanol: tetrahydrofuran (0.6 mL), adding 1N-aqueous sodium hydroxide solution (0.3 mL) and stirring at room temperature for 1 day, the reaction solution was directly added to Sephadex LH-20 (1: 2
Column purification with chloroform: methanol)
Compound 50 (3.6 mg, 70%) was obtained. Rf = 0.39 (chloroform: methanol = 3: 1) ¹ H-NMR (CD ₃ OD-CDCl ₃ ) δ: 4.842 (1H, d, J = 3.3 Hz, H
-1a), 4.292 (1H, d, J = 7.7Hz, H-1b), 0.897 (6H, t,
J = 6.6Hz, 2CH ₃ ).

Example 31 Compound 36 (178 mg, 196 μmol),
Rhamnose donor 23 (94 mg, 294 μmol) was dissolved in dichloromethane (5 mL), and methyl triflate (32 μL, 294 μmol) was dissolved.
mol), and the mixture was stirred at 0 ° C. to room temperature for 20 hours in the presence of MS4A (1 g). Methyl triflate (32 μL) was added, and the mixture was stirred for 5 hours. After neutralization with triethylamine, MS4A was filtered off and diluted with chloroform. The extract was washed successively with a saturated aqueous solution of sodium bicarbonate and saturated saline, and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (toluene: ethyl acetate = 5: 1) and LH-20 (chloroform: methanol = 1: 1) to obtain Compound 51 (93 mg, 40%). Rf = 0.24 (toluene: ethyl acetate = 5: 1) ¹ H-NMR (CDCl ₃ ) δ: 4.836 (1H, d, J = 3.5 Hz, H-1)
b), 4.043 (1H, br-s, H-4b), 2.139 (3H, s, Ac)
, 2.055 (3H, s, Ac), 1.984 (3H, s, Ac), 1.1
99 (3H, d, J = 6.2Hz, H-6a), 0.880 (3H, t, J
_{= 6.9Hz, C 12 H 24 Me} )

Example 32 Compound 51 (93 mg, 79 μmol) was dissolved in pyridine (5 mL), acetic anhydride (5 mL) was added, and the mixture was stirred for 12 hours in the presence of a catalytic amount of 4-dimethylaminopyridine. After evaporating the solvent, the residue was purified by silica gel column chromatography (toluene: ethyl acetate = 10: 1) to obtain Compound 52 (86 mg, 90%). Rf = 0.26 (toluene: ethyl acetate = 10: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.585 (1H, d, J = 2.6 Hz, H-
4b), 4.885 (1H, d, J = 3.7Hz, H-1b), 4.067 (1H
, br-t, J = 6.4Hz, H-5b), 3.952 (1H, dd, J =
3.3, 10.3Hz, H-3b), 2.135 (3H, s, Ac), 2.063
(3H, s, Ac), 1.972 (3H, s, Ac), 1.190 (3H,
d, 6.2Hz, H-6a), 0.880 (3H, t, 7.0Hz, C ₁₂ H ₂₄ M
e )

Example 33 Compound 52 (86 mg, 71 μmol) was suspended in a mixed solvent of toluene (7.5 mL) and water (2.5 mL), and triphenylphosphine (37 mg, 141 μmol) was added, followed by heating under reflux for 24 hours. After the solvent was distilled off, the residue was subjected to silica gel column chromatography (toluene: ethyl acetate = 3:
Purification by 1) yielded compound 53 (74 mg, 88%). Rf = 0.44 (toluene: ethyl acetate = 1: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.588 (1H, d, J = 2.6 Hz, H-4)
b), 4.893 (1H, d, J = 3.7Hz, H-1b), 2.138 (3H,
s, Ac), 2.115 (3H, s, Ac), 2.066 (3H, s, A
c), 1.973 (3H, s, Ac), 1.191 (3H, d, J = 6.2
Hz, H-6a) 0.881 ( 3H, t, J = 7.0Hz, C 12 H 24 Me)

Example 34 Compound 53 (74 mg, 62 μmol)
Dissolve in 1,2-dichloroethane (3 mL) and add lignoceric acid
(68.3 mg, 185 μmol), 2-chloro-1-methylpyridinium iodide (95 mg, 185 μmol), n -butylamine (69 mg
, 370 μmol) and stirred at room temperature for 20 hours. The reaction solution was diluted with chloroform, washed sequentially with a saturated aqueous solution of sodium bicarbonate and saturated saline, and dried over magnesium sulfate. After the solvent was distilled off, the residue was subjected to silica gel column chromatography.
(Toluene: ethyl acetate = 10: 1) to give compound 54 (77
mg, 82%). Rf = 0.23 (toluene: ethyl acetate = 5: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.952 (1H, d, J = 8.8 Hz, N
H), 5.498 (1H, br-s, H-4b), 4.882 (1H, d, J =
3.3Hz, H-1b), 2.132 (3H, s, Ac), 2.106 (3H,
s, Ac), 2.051 (3H, s, Ac), 1.981 (3H, s, A
c), 0.880 (6H, t , J = 6.6Hz, C 12 H 24 Me, C 22 H 44 M
e )

Example 35 Compound 54 (77 mg, 50 μmol) was dissolved in tetrahydrofuran (10 mL), and 1N-tetrabutylammonium fluoride / tetrahydrofuran solution
(5 mL) and stirred at 65 ° C. for 4 hours. After distilling off the solvent,
Pyridine (5 mL) and acetic anhydride (5 mL) were added, and the mixture was stirred for 15 hours in the presence of a catalytic amount of 4-dimethylaminopyridine. The solvent was distilled off, the residue was dissolved in chloroform, washed with saturated saline and dried over magnesium sulfate. After distilling off the solvent,
The residue was purified by silica gel column chromatography (toluene: ethyl acetate = 10: 1) to give Compound 55 (46 mg, 69).
%). Rf = 0.27 (toluene: ethyl acetate = 3: 1) ¹ H-NMR (CDCl ₃ ) δ: 6.370 (1H, d, J = 9.5 Hz, N
H), 5.456 (1H, d, J = 3.3Hz, H-4b), 5.434 (1H,
t, J = 10.3Hz, H-3Cer), 4.870 (1H, d, J = 3.7Hz
, H-1b), 2.125 (3H, s, Ac), 2.100 (3H, s, A
c), 2.056 (3H, s, Ac), 2.014 (3H, s, Ac),
1.988 (3H, s, Ac) 0.878 (6H, t, J = 6.9Hz, C
₁₂ H ₂₄ Me , C ₂₂ H ₄₄ Me )

Example 36 Compound 55 (46 mg, 34 μmol) was dissolved in a mixed solvent of ethyl acetate (5 mL) and methanol (5 mL), and 20% palladium hydroxide-carbon (46 mg) was added. And stirred at room temperature for 2 hours. After filtering off 20% palladium hydroxide-carbon, the solvent was distilled off, and the residue was purified by silica gel column chromatography (chloroform: methanol = 10: 1) to obtain Compound 56 (34 mg, 84%). Rf = 0.41 (chloroform: methanol = 20: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.336 (1H, d, J = 2.9 Hz, H-
4b), 4.886 (1H, d, J = 4.0Hz, H-1b), 2.143 (3H,
s, Ac), 2.139 (3H, s, Ac), 2.080 (3H, s, A
c), 2.061 (3H, s, Ac), 1.992 (3H, s, Ac),
0.880 (6H, t, J = 6.7Hz, C 12 H 24 Me, C 22 H 44 Me)

Example 37 Compound 56 (23 mg, 20 μmol) was dissolved in a mixed solvent of tetrahydrofuran (2 mL) and methanol (2 mL), a 1N aqueous sodium hydroxide solution (2 mL) was added, and the mixture was stirred at room temperature for 24 hours. . The solvent was distilled off, and the residue was purified by silica gel column chromatography (chloroform: methanol = 5: 1) and LH-20 (chloroform: methanol = 1: 1) to obtain Compound 57 (14 mg, 75%). ¹ H-NMR (CD ₃ OD: CDCl ₃ = 1: 1) δ: 4.865 (1H, d, J =
3.7Hz, H-1b), 4.770 (1H, br-s, H-1a), 0.889 (6H
, t, J = 6.9Hz, C ₁₂ H ₂₄ Me , C ₂₂ H ₄₄ Me )

Example 38 Compound 37 (77 mg, 84 μmol),
Rhamnose donor 23 (41 mg, 126 μmol) was dissolved in dichloromethane (5 mL), and methyl triflate (14 μL, 127
μmol), and the mixture was stirred at 0 ° C. to room temperature for 48 hours in the presence of MS4A (1 g). After neutralization with triethylamine, MS4A was filtered off and diluted with chloroform. The extract was washed successively with a saturated aqueous solution of sodium bicarbonate and saturated saline, and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (toluene: ethyl acetate = 5: 1) to give Compound 58 (45 mg, 45 mg).
%). Rf = 0.33 (toluene: ethyl acetate = 5: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.404 (1H, br-t, J = 9.5Hz,
H-4Cer), 5.3 (1H, m, H-5Cer), 4.770 (1H, br-s,
H-1a), 4.281 (1H, d, J = 7.7Hz, H-1b), 3.992
(1H, br-s, H-4b), 2.152 (3H, s, Ac), 2.064
(3H, s, Ac), 1.997 (3H, s, Ac), 1.212 (3H, d
, J = 6.2Hz, H-6a), 0.881 (1H, t, J = 7.0Hz,
C ₁₂ H ₂₄ Me )

Example 39 Compound 58 (45 mg, 38 μmol) was dissolved in pyridine (5 mL), acetic anhydride (5 mL) was added, and the mixture was stirred for 12 hours in the presence of a catalytic amount of 4-dimethylaminopyridine. After evaporating the solvent, the residue was purified by silica gel column chromatography (toluene: ethyl acetate = 5: 1),
Compound 59 (45 mg, 96%) was obtained. Rf = 0.38 (toluene: ethyl acetate = 5: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.559 (1H, d, J = 2.2 Hz, H-
4b), 5.398 (1H, dd, J = 9.2, 11.0Hz, H-4Cer),
4.742 (1H, br-s, H-1a), 4.329 (1H, d, J = 7.3H
z, H-1b), 2.154 (3H, s, Ac), 2.147 (3H, s,
Ac), 2.073 (3H, s, Ac), 1.990 (3H, s, Ac) 1.2
00 (3H, d, J = 6.2Hz, H-6a), 0.880 (3H, t, J =
6.9Hz, C ₁₂ H ₂₄ Me)

Example 40 Compound 59 (45 mg, 36 μmol) was suspended in a mixed solvent of toluene (7.5 mL) and water (2.5 mL).
Add triphenylphosphine (19.2 mg, 73 mmol) and add 18
Heated to reflux for an hour. After evaporating the solvent, the residue was purified by silica gel column chromatography (chloroform: methanol = 3: 1) to obtain Compound 60 (42 mg, 97%). Rf = 0.30 (toluene: ethyl acetate = 1: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.557 (1H, br-s, H-4b), 2.15
7 (3H, s, Ac), 2.144 (3H, s, Ac), 2.072
(3H, s, Ac), 1.985 (3H, s, Ac), 1.200 (3H,
d, J = 6.2Hz, H-6a), 0.880 (3H, t, J = 6.7Hz
, C ₁₂ H ₂₄ Me )

Example 41 Compound 60 (44 mg, 37 μmol) 1,
Dissolve in 2-dichloroethane (3 mL) and add lignoceric acid (4
1 mg, 74 μmol), 2-chloro-1-methylpyridinium iodide (28 mg, 74 μmol), n -butylamine (19 mg, 148
μmol) and stirred at room temperature for 18 hours. The reaction solution was diluted with chloroform, washed sequentially with a saturated aqueous solution of sodium bicarbonate and saturated saline, and dried over magnesium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography (toluene: ethyl acetate = 3: 1) to obtain compound 61 (33 mg, 5 mg).
8%). Rf = 0.36 (toluene: ethyl acetate = 3: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.662 (1H, d, J = 9.2 Hz, N
H), 5.584 (1H, d, J = 2.2Hz, H-4b), 4.755 (1H,
s, H-1a), 4.404 (1H, d, J = 7.0 Hz, H-1b),
2.175 (3H, s, Ac), 2.148 (3H, s, Ac), 2.075
(3H, s, Ac), 1.993 (3H, s, Ac), 1.206 (3H, s, Ac)
d, J = 6.2Hz, H-6a), 0.880 (6H, t, J = 6.8Hz,
C ₁₂ H ₂₄ Me , C ₂₂ H ₄₄ Me ),

Example 42 Compound 61 (33 mg, 21 μmol) was dissolved in tetrahydrofuran (5 mL), and 1N-tetrabutylammonium fluoride / tetrahydrofuran solution was dissolved.
(2.5 mL), and the mixture was stirred at 70 ° C. for 15 hours. After evaporating the solvent, pyridine (5 mL) and acetic anhydride (5 mL) were added, and a catalytic amount of
The mixture was stirred for 12 hours in the presence of DMAP. The solvent is distilled off and the residue is subjected to silica gel column chromatography (toluene: ethyl acetate
= 3: 1) and LH-20 (chloroform: methanol = 1: 1) to obtain Compound 62 (25 mg, 88%). Rf = 0.25 (toluene: ethyl acetate = 3: 1) ¹ H-NMR (CDCl ₃ ) δ: 5.954 (1H, d, J = 9.2 Hz, N
H), 5.517 (1H, br-s, H-4b), 2.151 (3H, s, Ac)
, 2.071 (3H, s, Ac), 2.042 (3H, s, Ac), 2.0
27 (3H, s, Ac), 1.997 (3H, s, Ac), 0.880 (6H
, T, J = 6.8Hz, C 12 H 24 Me, C 22 H 44 Me)

Example 43 Compound 62 (25 mg, 19 μmol) was dissolved in a mixed solvent of ethyl acetate (2 mL) and methanol (2 mL), and 20% palladium hydroxide-carbon (25 mg) was added. Stirred at room temperature for 3 hours. The solvent was distilled off, and the residue was purified by silica gel column chromatography (chloroform: methanol = 10: 1). This was dissolved in a mixed solvent of tetrahydrofuran (2 mL) and methanol (2 mL), and a 1N aqueous sodium hydroxide solution (2 mL) was added.
Stirred for hours. The solvent was distilled off, and LH-20 (chloroform:
Purification with methanol = 1: 1) gave Compound 63 (8.5 mg, 47%). ¹ H-NMR (CD ₃ OD: CDCl ₃ = 1: 1) δ: 4.224 (1H, d, J =
7.3Hz, H-1b), 0.891 (6H, t, J = 6.8Hz, C 12 H 24 Me
, C ₂₂ H ₄₄ Me )

<Promotion of lymphocyte proliferation in mouse lymphocyte blastogenesis> BALB / c mouse (female, 8 to 1
Lymphocytes collected from the spleen of a 0-week-old (Japan SLC) according to a conventional method were prepared at 3 × 10 6 cells / ml using 10% FCS-RPMI1640 as a medium. Using a flat-bottom 96-well plate, 10 μl of a sample prepared at 10 μM with physiological saline was added to 100 μl of the cell suspension,
After culturing for 3 days at 37 ° C and 5% CO ₂ ,
Cell proliferation was measured by MTT assay. The results are shown in Table 1. Each compound showed a remarkable lymphocyte proliferation promoting effect. <Anti-tumor activity against B16 mouse melanoma cells in the abdominal cavity> B16 mouse melanoma cells 8 × in the abdominal cavity of BDF1 mice (female, 6 weeks old, Japan SLC)
105 cells / mouse were implanted (implantation day 0), and on days 1, 5 and 9 after implantation, a dose of 1 m
g / kg of a sample prepared with a mouse weight of 2
0.2 ml per 0 g was intraperitoneally administered, and the number of days until death was measured. The experiment was performed using 6 to 9 mice per group, and the control group was administered with physiological saline. The results are shown in Table 2. Each compound showed significant antitumor activity.

[0070]

[Table 1]

[0071]

[Table 2] Compound Nos. 19 , 21 , 45 , 50 , 57 , 63 and 6
The compound of the present invention represented by No. 4 is useful in that it has immunostimulatory activity and antitumor activity. 1) Immunostimulatory activity As shown in the above experimental examples, the compound of the present invention exhibited lymphocyte proliferation promoting activity, ie, immunostimulatory activity, in mouse lymphocyte blastogenesis. 2) Antitumor activity The compound of the present invention exhibited antitumor activity against B16 mouse melanoma cells in the abdominal cavity as shown in the above experimental examples. 3) Immunomodulators, especially immunostimulators and antitumor agents As described above, it was revealed that the compounds of the present invention exhibit immunostimulatory activity and antitumor activity. Therefore, the compound of the present invention can be used as an immunostimulant or an antitumor agent. Since the compound of the present invention has immunostimulatory activity, it can be used as a therapeutic drug for bone marrow suppression caused by administration of an anticancer drug or radiation therapy, and a therapeutic drug for various infectious diseases and immunodeficiencies. Further, since it acts on immunocompetent cells, it can be used as an immunomodulator, for example, as a therapeutic drug for autoimmune diseases such as rheumatoid arthritis.

[Brief description of the drawings]

FIG. 1 is a flow chart showing a production process of an example compound according to the present invention.

FIG. 2 is a flow chart showing a production process of an example compound according to the present invention.

FIG. 3 is a flow chart showing a production process of an example compound according to the present invention.

FIG. 4 is a flow chart showing a process for producing an example compound according to the present invention.

FIG. 5 is a flow chart showing a process for producing an example compound according to the present invention.

FIG. 6 is a flow chart showing a process for producing an example compound according to the present invention.

FIG. 7 is a flow chart showing a process for producing an example compound according to the present invention.

FIG. 8 is a flow chart showing a process for producing an example compound according to the present invention.

FIG. 9 is a flowchart showing the steps for producing the compound of the example according to the present invention.

FIG. 10 is a flowchart showing the steps for producing the compound of the example according to the present invention.

FIG. 11 is a flowchart showing the steps for producing the compound of the example according to the present invention.

Continued on the front page (72) Isao Suda, Inventor 1780 Kitano, Tokorozawa-shi, Saitama Nisshin Foods Co., Ltd.

Claims (18)

[Claims] 1. Monosaccharide → Gal1 → 1′Cer (C24, Sat.)
A compound represented by the structural formula: 2. The compound according to claim 1, wherein the monosaccharide has a glycosidic bond at the 3-position of Gal. 3. The monosaccharide comprises Fuc, Gal, and Rh.
The compound according to claim 2, which is selected from the group consisting of a. 4. The compound according to claim 1, wherein the monosaccharide has a glycosidic bond at the 4-position of Gal. 5. The monosaccharide comprises Fuc, Gal, and Rh.
The compound according to claim 4, which is selected from the group consisting of a. 6. The compound according to claim 1, wherein the monosaccharide has a glycosidic bond at position 6 of Gal. 7. The monosaccharide is composed of Fuc, Gal, and Rh.
The compound according to claim 6, which is selected from the group consisting of: a. 8. Fucβ1 → 3Galα1 → 1′Cer
A compound represented by the structural formula (C24, Sat.). 9. Fucβ1 → 4 (Fucα1 → 3) Ga
A compound represented by a structural formula of lα1 → 1′Cer (C24, Sat.). 10. Fucβ1 → 6Galα1 → 1′Ce
A compound represented by the structural formula r (C24, Sat.). 11. Galβ1 → 6Galα1 → 1′Ce
A compound represented by the structural formula r (C24, Sat.). 12. Rhaα1 → 6Galα1 → 1′Ce
A compound represented by the structural formula r (C24, Sat.). 13. Rhaα1 → 6Galβ1 → 1′Ce
A compound represented by the structural formula r (C24, Sat.). 14. Galβ1 → 6Galα1 → 1′Ce
A compound represented by the structural formula r (C24, Sat.). 15. The compound according to any one of claims 1 to 14, or Rhaα1 → 6Galβ1 → 1 ′.
A medicament containing an effective amount of a compound represented by the structural formula of Cer (double bond between C24 and C4-C5). 16. The medicament according to claim 15, which is an immunomodulator. 17. The medicament according to claim 15, which is an immunostimulant. 18. The medicament according to claim 15, which is an antitumor agent.