JPH06247995A - New sialyl(alpha2-6)lactotetraosylceramide - Google Patents

Abstract

PURPOSE:To obtain the subject new compound composed of sialyl (alpha 2-6) lactotetraosylceramide, having a strong binding activity against influenza virus A, B and capable of effectively removing these viruses for prevention of infec tion therewith. CONSTITUTION:An N-acetylneuraminic acid methyl ester of formula I (Ac is acetyl; Me is methyl) is reacted with a compound of formula II [SE is 2-(trimethylsilyl)ethyl; R is benzyl, etc.] in the presence of a dehydration agent and the hydroxyl groups are subsequently protected. The resultant compound is subjected to glycosylatio in the presence of a compound of formula III (R<1> is benzyl; R<12> is H; R<13> and R<14> are each benzylidene; R<15> is OSE) and dimethyl(methylthio)sulfonium triflate and a compound of formula IV (Bz is benzoyl) is subsequently reacted therewith, thus synthesizing the objective new compound of formula V (NeuAc is N-acetylneuramic acid residue; Gal is galactose residue; GlcNAc is N-acetylglucosamine residue; Glc is glucose residue; Cer is ceramide).

Description

Detailed Description of the Invention

[0001]

The present invention relates to the following formula (29) NeuAcα2-6Galβ1-3GlcNAc β1-3Galβ1-4Glcβ1-Cer (29) (wherein NeuAc is an N-acetylneuraminic acid residue,
Gal represents a galactose residue, GlcNAc represents an N-acetylglucosamine residue, Glc represents a glucose residue, and Cer represents a ceramide group), and relates to a novel sialyl (α2-6) lactotetraosylceramide.

[0002]

2. Description of the Related Art Influenza virus is a pathogen of serious respiratory infections that causes an explosive epidemic in a short period of time.
By making significant antigenic mutations, it escapes attack by host antibodies.

[0003] Influenza virus belongs to the family Orthomyxoviridae, has a spherical particle shape of 80 to 100 nm, and is a kind of so-called envelope virus having a lipid bilayer membrane derived from a host. Inside the envelope,
There are membrane proteins and ribonucleoproteins (consisting of RNP, one single-stranded RNA, nucleoprotein, and three RNA polymerases, forming eight segments). Influenza viruses are classified into A, B, and C types mainly due to the difference in the antigenicity of this nucleoprotein. A, B
The hemagglutinin (HA, hemagglutinin) and neuraminidase (NA) glycoproteins are prominent on the type I viral membrane, and a type of glycoprotein called HE (gp88, hemagglutinin-esterase) is present on the type C membrane. It is protruding.

[0004]

Infection of cells with influenza virus is carried out by adsorbing to the sialo glycoconjugate, which is a receptor sugar chain existing on the cell surface, via HA and then invading the cell by endocytosis. , The lysosomes and endosomes are taken in, and the pH in these granules is weakly acidic, and under these conditions, it is considered that the viral membrane and the onegella membrane are fused to release RNP into the cells. Among these influenza viruses, the A and B type viruses are particularly pathogenic, and in the A type, subtypes (HA: 1 to 14, NA: 1 to 9) occur in HA and NA, causing the pandemic. Therefore, the present invention provides a compound capable of effectively removing the virus for protection against such infections.

[0005]

[Means for Solving the Problems] The inventors of the present invention have diligently studied gangliosides which have a high binding activity (receptor activity) to influenza A and B viruses and have a removable sialoic acid. As a result, the inventors newly synthesized the following formula (29) NeuAcα2-6Galβ1-3GlcNAc β1-3Galβ1-4Glcβ1-Cer (29) (wherein NeuAc, Gal, GlcNAc, Glc, and Cer have the same meanings as described above). ), Sialyl (α2-6) lactotetraosylceramide, which is a ganglioside that binds to A and B HA of influenza virus very effectively.

The present invention has been completed based on the above findings, and has the following formula (29) NeuAcα2-6Galβ1-3GlcNAc β1-3Galβ1-4Glcβ1-Cer (29) (wherein NeuAc, Gal, GlcNAc, Glc, and Cer have the same meanings as above), and are sialyl (α2-6) lactotetraosylceramide.

First, the following formula (29) NeuAcα2-6Galβ1-3GlcNAc β1-3Galβ1-4Glcβ1-Cer (29) in the present invention (wherein NeuAc, Gal, GlcNAc, Glc, and Cer have the same meanings as described above) Sialyl (α2-6) lactotetraosylceramide represented by the following general formula [VII]

[Chemical 1] (Wherein, R21 is _{-NHCO (CH 2) 16 Me,} R11,
R13, R14, R21, R22, R23, and R24 each have a structure represented by a hydrogen atom), and this sialyl (α2-6) lactotetraosylceramide (2
In obtaining 9), the reaction steps are exemplified below.

First step N-acetylneuraminic acid ────── → compound (3) Second step compound (3) + compound (2) ───── → compound (8) third step compound ( 8) ──────────── → compound (9) 4th step compound (9) ──────────── → compound (10) 5th step compound (10) ─────────── → Compound (11) 6th step Compound (11) + Compound (12) ─── → Compound (16) 7th step Compound (16) ─────── ──── → Compound (17) Eighth Step Compound (17) ──────────── → Compound (18) Ninth Step Compound (18) ──────────── → Compound (19) 10th step Compound (19) + Compound (25) ─── →→ Compound (26) 11th step Compound (26) ─────────── -> Compound (27) 12th step Compound (27) --------------------------------------------------------------------- → Compound (28) 13th step Compound (28) ---- ─────────-→ Compound ( 29)

Step 1 Compound (3) has the following general formula [I]:

[Chemical 2] (In the formula, Ac represents an acetyl group and SE represents a 2- (trimethylsilyl) ethyl group). A methyl α-triglucoside derivative of N-acetylneuraminic acid (J.Ca).
rbohydr. Chem. , 8, 265 (198
9)).

Step 2 Compound (8) is obtained by reacting compound (3) above with the following general formula [I
I]

[Chemical 3] (Wherein Bn represents a benzyl group) (2) (J. Carbohydr. Chem., 8 , 2
65 (1989)) and, for example, the compound (3) in an equimolar amount or more, preferably 1.5 times or more as compared with the compound (2), is used to remove a dehydrating agent such as molecular sieves in a solvent of dry acetonitrile. Dimethyl (methylthio) sulfonium that promotes glucosylation in the presence of
Triflate [dimethyl (methyl-th
io) sulfonium triflate (DMT
ST)] in the presence of the compound of formula (III)

[Chemical 4] (In the formula, R1 is -OSE, R2 is a hydrogen atom, and R3 is Bn.
And Bn and SE mean the same groups as described above).

Third Step The compound (9) is a dibenzoate derivative of the compound (8), and for example, benzoyl chloride is present in the presence of pyridine in dichloromethane in an amount of 2 times or more moles as compared with the compound (8), preferably. May be reacted using 2.5 times or more moles of the compound (9)
(In the formula, R1 is -OSE, R2 is a benzoyl group (B
z) and R3 represent Bn, and Bn and SE mean the same groups as described above).

Step 4 Compound (10) is an acetyl derivative of group R1 of compound (9), eg boron trifluoride eseleite in dry toluene.
The reaction may be performed by adding acetic anhydride in the presence of deetherate, and the compound (10) can be obtained by reacting the compound represented by the general formula [III] (wherein R 1 is —OAc, R 2 is Bz, R 2
3 represents Bn, and Bn, Ac and Bz mean the same groups as described above).

Fifth Step Compound (11) is a methylthio derivative of group R1 of compound (9), for example by adding an excess mole of (methylthio) trimethylsilane in the presence of boron trifluoride eseleite in dichloromethane. The compound (10) may be reacted with the compound of the general formula [III] (wherein R 1 is a methylthio group (SMe), R 2 is Bz, R 3
Represents Bn, and Bn and Bn mean the same groups as above)
It is represented by.

Step 6 The compound (16) is obtained by reacting the compound (11) with the following general formula [IV].

[Chemical 5] (In the formula, R11 is Bn, R12 is a hydrogen atom, R13 and R14 are benzylidene groups, R15 is OSE, and B is
n and SE mean the same groups as described above) (12) [Carbohydr. Res. , 200 , 2
69 (1990)] with, for example, the compound (11) in an equimolar amount or more, preferably 1.5 times or more as compared with the compound (12), in the presence of DMTST in dichloromethane. The compound (16) thus obtained is represented by the following general formula [V]

[Chemical 6] (Wherein R3 and R11 are Bn, R13 and R14
Is a benzylidene group, R15 is an OSE, R16 is a hydrogen atom, and Bn and SE are the same groups as described above).

Step 7 The compound (17) is the same as the group R3, R in the compound (16).
Acetyl derivatives of 11, R13 and R14,
For example, compound (16) is added to Pd in an acetic acid-ethanol solvent.
Hydrogenation in the presence of —C, followed by acetylation with acetic anhydride in the presence of pyridine, this compound (1
7) is the above general formula [V] (wherein R3, R11, R1
3 and R14 are acetyl groups, R15 is OSE, R16
Represents a hydrogen atom, and Bn and SE mean the same groups as described above).

Eighth step Compound (18) is an —OH form obtained by de-SE conversion of group R15 of compound (17) obtained above, and can be obtained, for example, by treating with trifluoroacetic acid in dichloromethane. This compound (18) has the general formula [V] above.
(In the formula, R3, R11, R13, and R14 are acetyl groups, R15 is an -OH group, R16 is a hydrogen atom, and B is
n and SE mean the same groups as described above).

Step 9 The compound (19) is the α of the compound (18) obtained above.
A trichloroacetimidate derivative, for example 1,8-diazabicyclo [5.4.
0] Undec-7-ene [1,8-diazabic
The compound (19) is obtained by treating with trichloroacetonitrile in the presence of yclo [5.4.0] undec-7-ene], and this compound (19) is represented by the above general formula [V] (in the formula, R3, R11, R13 and R14 is an acetyl group,
R15 and R16 work together = OC (= NH) CCl
₃ is shown).

Step 10 Compound (26) is the same as compound (19) obtained above.
The following formula [VI]

[Chemical 7] (In the formula, Bz means the same group as described above) (25) [(2S, 3R, 4E) -2-azido
-3-O-benzoyl-4-octadecene
-1,3-diol: Angew. Chem. Int.
Ed. Engl. , 25 , 725 (1986)], and may be reacted in the presence of boron trifluoride eseleite in dichloromethane, for example, and the compound (26) is represented by the following general formula [VII]

[Chemical 8] (In the formula, R11, R13, R14 and R23 represent an acetyl group, R22 represents Bz, R21 represents an azido group, and Bz represents the same group as described above).

Eleventh step The compound (27) is obtained by the selective reduction of the azido group of the group R21 of the compound (26) obtained above with hydrogen sulfide. For example, hydrogen sulfide is prepared in an aqueous 83% pyridine solution. Obtained by aeration,
This compound (27) is represented by the above general formula [VII] (in the formula, R
11, R13, R14 and R23 are acetyl groups, R2
2 represents Bz, R21 represents an amino group, and Bz means the same group as described above).

Step 12 Compound (28) is obtained, for example, from compound (2) obtained above.
This is obtained by reacting octadecanoic acid in the presence of a dehydrating condensing agent such as 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride in dichloromethane with the amino group R21 in 7). The compound (28) is represented by the above general formula [VII] (wherein R11,
R13, R14 and R23 are acetyl groups, R22 is B
z and R21 each represent —NHCO (CH ₂ ) ₁₆ Me, and Bz represents the same group as described above.

Step 13: The desired compound (29) is obtained by deprotecting the protected hydroxyl group of the compound (28) obtained above. For example, the compound (28) in methanol. Sodium methoxide
The compound (29) can be obtained by treating with general formula [VII] (wherein R21 is -N).
HCO (CH ₂ ) ₁₆ Me, R11, R13, R14, R2
Sialyl (α2-6) lactotetraosylceramide represented by 1, R22, R23, and R24 all represent hydrogen atoms is obtained.

In these reactions, purification may be carried out by an appropriate simple purification means, for example, silica gel column chromatography or Sephadex LH-20 column chromatography. Furthermore, this sialyl (α
2-6) Lactotetraosylceramide (29) can be made into a salt. Examples of such a salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium and ammonium. Examples include salt. In addition, the sialyl (α2-6) lactotetraosylceramide (29) of the present invention may be used after being adsorbed and immobilized by an adsorbent such as silica gel or activated carbon,
Further, by utilizing a hydroxyl group in the ceramide molecule of sialyl (α2-6) lactotetraosylceramide (29), a publicly known cross-linking agent is appropriately used to carry out carboxyl group, amino group, imino group, hydroxyl group or its chemical Covalently immobilized with a polymer carrier having a reactive derivative, for example, carboxymethyl cellulose, carboxyethyl cellulose, aminated glass, amino group-containing polyacrylonitrile, polyglutamic acid, polylysine, polyethylene glycol, cellulose, agarose, dextran gel. May be used as a thing.

[0023]

The present invention will be described below with reference to examples.
The present invention is not limited thereby.

Example 1 2- (Trimethylsilyl) ethyl O- (methyl 5-
Acetamide-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosylonate)-(2 → 6) -3-
O-benzyl-β-D-galactopyranoside; Synthesis of compound (8) Compound (2) (1.0 g, 2.7 mmol: J. Car.
bohydr. Chem. , Vol. 8, p. 265
1989) and compound (3) (2.2 g, 4.37 mmo)
l: J. Carbohydr. Chem. , Vol.
8, p. 265, 1989) in 2.5 ml of anhydrous acetonitrile solution and molecular sieves 3A (MS-
3A, 2.0 g) was added and the mixture was stirred at room temperature for 16 hours, and then -4
Cooled to 0 ° C. 4. Dimethyl (methylthio) sulfonium triflate (DMTST) was added to the cooled reaction solution.
After adding 8 g (22.4 mmol), -15 ° C.
Vigorously stirred for 24 hours. After the reaction was completed, the precipitate was collected by filtration and washed with dichloromethane. The combined solution of the precipitate and the washing solution was first washed with a 1M sodium hydrogen carbonate solution, then dried over anhydrous sodium sulfate and concentrated, and then silica gel chromatography (200 g) was used to develop a solvent dichloromethane-
Elution and purification with methanol (30: 1) gave 1.03 g (yield 45%) of compound (8) as amorphous crystals. [Α] D-16.2 ° (c 1.1, chloroform); 1H NMR (CDCl3) Neu5Acun.
it δ 1.87 (s, 3H, AcN), 1.99,
2.00, 2.09, 2.11 (4s, 12H, 4Ac
O), 2.16 (dd, 1H, Jgem = 12.6H)
z, J3e, 4 = 4.8 Hz, H-3e), 3.79.
(S, 3H, MeO), 4.75 (m, 1H, H-
4), 5.29 (dd, 1H, J6, 7 = 2.0 Hz,
J7.8 = 8.1 Hz, H-7), and 5.33.
(M, 1H, H-8); Gal unit δ 0.9
8 (m, 2H, Me3SiCH2CH2), 4.27
(D, 1H, J1, 2 = 7.8 Hz, H-1), 4.6
7, 4.74 (2d, 2H, PhCH2O), and
7.02-7.46 (m, 5H, Ph); Anal. Calcd for C38H57NO18
Si (843.9): C, 54.08%, H, 6.81
%, N, 1.66%; Found: C, 53.87%,
H, 7.07%, N, 1.50%.

Example 2 2- (Trimethylsilyl) ethyl O- (methyl 5-
Acetamide-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosylonate)-(2 → 6) -2,
4-di-O-benzoyl-3-O-benzyl-β-D-
Galactopyranoside; Synthesis of compound (9) 5 ml of a dichloromethane solution containing compound (8) (395 mg, 0.47 mmol) was cooled to 0 ° C, 0.5 ml of pyridine and 0.16 ml of benzoyl chloride.
A solution obtained by mixing (1.33 mmol) was added with stirring, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, 1 ml of methanol was added, and the mixture was stirred at room temperature for 20 minutes, and extracted with dichloromethane. The extract was washed with 2M-hydrochloric acid solution, 1M-sodium hydrogen carbonate solution and water, dried over anhydrous sodium sulfate and concentrated. Using silica gel chromatography (40 g), developing solvent ethyl acetate-hexane (2:
The target compound (9) was obtained as amorphous crystals by elution and purification in 1) to obtain 301 mg (yield 61%). [Α] D + 39.0 ° (c 1.26, chloroform); 1H NMR (CDCl3) Neu5Ac un.
it δ 1.96 (s, 3H, AcN), 2.11
2.12, 2.18, 2.22 (4s, 12H, 4Ac
O), 2.64 (dd, 1H, Jgem = 12.8H)
z, J3e, 4 = 4.8 Hz, H-3e), 3.37.
(S, 3H, MeO), 4.41 (dd, 1H, J8,
9 = 2.6 Hz, Jgem = 12.5 Hz, H-9),
and 5.46 (m, 1H, H-8); Galun.
it δ 0.97 (m, 2H, Me3SiCH2CH
2), 3.88 (dd, 1H, J2, 3 = 9.9Hz,
J3,4 = 3.3 Hz, H-1), 4.61, 4.84
(2d, 2H, PhCH2O), 4.70 (d, 1H,
J1,2 = 8.1 Hz, H-1), 5.55 (dd, 1)
H, H-2), 6.02 (broad d, 1H, H-
4), and 7.12-8.26 (m, 15H, 3P.
h); Anal. Calcd for C52H65NO20
Si (1052.2): C, 59.36%, H, 6.2
3%, N, 1.33%: Found: C, 59.41
%, H, 6.43%, N, 1.30%.

Example 3 O- (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosiro )-(2 → 6) -1-O-acetyl-2,4-di-O
-Benzoyl-3-O-benzyl-β-D-galactopyranose; Synthesis of compound (10) Mixed solution of compound (9) (301 mg, 0.29 mmol) in toluene (3 ml) -acetic anhydride (0.4 ml) And boron trifluoride etherate 0.08m
1 was added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, 10 ml of dichloromethane was added, washed with 1M-sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate, concentrated, and eluted with ethyl acetate-hexane (4: 1) as a developing solvent using silica gel chromatography (40 g). 174 mg (61% yield) of the target compound (10) as amorphous crystals.
Obtained. [Α] D + 58.5 ° (c 1.0, chloroform); 1H NMR (CDCl3) Neu5Ac un
it δ 1.87 (s, 3H, AcN), 2.55
(Dd, 1H, Jgem = 13.0Hz, J3e, 4 =
4.6 Hz, H-3e), 3.29 (s, 3H, Me
O), and 5.38 (m, 1H, H-8); Gal
unit δ 4.29 (dd, 1H, J2, 3 = 1
2.5 Hz, J3, 4 = 2.6 Hz, H-3), 4.5
3, 4.77 (2d, 2H, PhCH2O), 5.58
(Dd, 1H, J1,2 = 8.4 Hz, H-2), 5.
87 (d, 1H, H-1), 5.96 (broad
d, 1H, H-4), and 7.03-8.16.
(M, 15H, 3Ph); O-acetylgroup
s δ 2.02, 2.03, 2.04, 2.07,
2.13 (5s, 15H, 5AcO); Anal. Calcd for C49H55NO21
(994.0): C, 59.21%, H, 5.58%,
N, 1.41%; Found: C, 59.08%, H,
5.58%, N, 1.41%.

Example 4 Methyl O- (methyl 5-acetamide-4,7,
8,9-Tetra-O-acetyl-3,5-dideoxy-
D-glycero-α-D-galacto-2-nonuropyranosylonate)-(2 → 6) -2,4-di-O-benzoyl-3-O-benzyl-1-thio-β-D-galacto Pyranoside; Synthesis of compound (11) 2 ml of dichloromethane
(10) (174 mg, 0.17 mm) dissolved in
ol) solution, (methylthio) trimethylsilane 5
2.6 mg (0.43 mmol) and boron trifluoride etherate 0.4 ml were added with stirring,
Stir at room temperature for 2 hours. After completion of the reaction, dichloromethane 3
After adding 0 ml, washing with 1M-sodium hydrogen carbonate solution, drying over anhydrous sodium sulfate and concentrating, and then eluting and purifying with silica gel chromatography (30 g) as a developing solvent dichloromethane-methanol (80: 1) to obtain the target. 150 mg (yield 87%) of compound (11) was obtained. [Α] D + 53.0 ° (c 0.96, chloroform); 1H NMR (CDCl3) Neu5Ac un
it δ 1.87 (s, 3H, AcN), 2.02
2.03, 2.09, 2.13 (4s, 12H, 4Ac
O), 2.55 (dd, 1H, Jgem = 13.0H)
z, J3e, 4 = 4.6 Hz, H-3e), 3.34.
(S, 3H, MeO), 4.79 (m, 1H, H-
4), and 5.38 (m, 1H, H-8); Gal
unit δ 2.29 (s, 3H, MeS), 4.
54, 4.79 (2d, 2H, PhCH2O), 4.5
5 (d, 1H, J1,2 = 9.9Hz, H-1), 5.
55 (t, 1H, J1, 2 = J2, 3 = 9.9Hz, H
-2), 5.97 (broad s, 1H, J3, 4 =
2.7 Hz, H-4), and 7.05-8.20
(M, 15H, 3Ph); Anal. Calcd for C45H55NO19
S (982.0): C, 58.71%, H, 5.65
%, N, 1.43%: Found; C, 58.71%,
H, 5.78%, N, 1.42%.

Example 5 2- (Trimethylsilyl) ethyl O- (methyl 5-
Acetamide-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosylonate)-(2 → 6) -O-
(2,4-di-O-benzoyl-3-O-benzyl-β
-D-galactopyranosyl)-(1 → 3) -O- (2-
Acetamide-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(1 → 3) -O-
(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1 → 4) -2,3,6-tri-O-benzyl-β-D-glucopyranoside; Compound (16 ) Compound (12) (38.4 mg, 0.03 mmol: C
arbohydr. Res. , Vol. 200, p26
9, 1990) and compound (11) (60 mg, 0.06)
The powder of Molecular Sieves 4A (MS-4A, 700 mg) was added to a solution of 7 ml of dichloromethane containing (mmol), and the mixture was stirred at room temperature for 5 hours. The solution was cooled to 0 ° C., dimethyl (methylthio) sulfonium triflate (DMTST, 260 mg, 1.0 mmol) was added, and the reaction was carried out for 14 hours while maintaining 0 ° C. Then, the precipitate in the reaction solution was collected, washed and extracted with dichloromethane, the dichloromethane solution was washed with water, and dried over anhydrous sodium sulfate. The dichloromethane solution was concentrated and the residue was eluted with ethyl acetate-hexane (4: 1) as a developing solvent using a silica gel column (50 g) to obtain the target compound (16).
Was obtained in 39 mg (58% yield). 1H NMR (CDCl3) δ 1.00 (m, 2H,
Me3SiCH2CH2), 1.68, 1.87 (2
s, 6H, 2AcN), 1.87-2.09 (4s, 1
2H, 4AcO), 2.58 (dd, 1H, Jgem =
12.5Hz, J3e-eq, 4e = 4.4Hz, H-
3e-eq), 3.06 (s, 3H, MeO), 4.3
4 (d, 1H, J1b, 2b = 7.3 Hz, H-1
b), 4.63 (d, 1HJ1d, 2d = 7.9 Hz,
H-1d), 5.39 (m, 1H, H-8e), 6.9.
3-8.16 (m, 50H, 10Ph); Anal. Calcd for C121H138N2
O35Si (2208.5); C, 68.81%, H,
6.30%, N, 1.27%: Found; C, 68.
65%, H, 6.49%, N, 1.26%.

Example 6 2- (Trimethylsilyl) ethyl O- (methyl 5-
Acetamide-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosylonate)-(2 → 6) -O-
(3-O-acetyl-2,4-di-O-benzoyl-β
-D-galactopyranosyl)-(1 → 3) -O- (2-
Acetamide-4,6-di-O-acetyl-2-deoxy-β-D-glucopyranosyl)-(1 → 3) -O-
(2,4,6-tri-O-acetyl-β-D-galactopyranosyl)-(1 → 4) -2,3,6-tri-O-acetyl-β-D-glucopyranoside; Compound (17) Synthesis of compound (16) (64) in 60 ml of 80% aqueous acetic acid solution
(7 mg, 0.29 mmol) was heated and stirred at 60 ° C. for 24 hours, and after the reaction, the solution was concentrated. This residue was hydrogenated with 1.2 g of 10% palladium carbon (Pd-C) in a mixed solvent of 80 ml of ethanol and 20 ml of acetic acid, and 45 ° C.
React for 48 hours. After the reaction, palladium carbon was filtered off and the filtrate was concentrated. Further, the residue was reacted in a mixed solvent of 6 ml of acetic anhydride and 8 ml of pyridine at 45 ° C. for 3 days. The reaction solution was concentrated, and the residue was eluted with a silica gel column (100 g) as a developing solvent dichloromethane-methanol (50: 1) to give the compound (1
7) was obtained in 350 mg (64% yield). [Α] D + 23.6 ° (c1.0, chloroform); 1
1 H NMR (CDCl3) δ 0.89 (m, 2H, M
e3SiCH2CH2), 1.85, 1.88 (2s,
6H, 2AcN), 1.99-2.17 (13s, 39).
H, 13AcO), 2.50 (dd, 1H, Jgem =
12.8Hz, J3e-eq, 4e = 4.0Hz, H-
3e-eq), 3.29 (s, 3H, MeO), 4.1
0 (dd, 1H, Jgem = 12.5Hz, J8e, 9
e = 4.0 Hz, H-9e), 4.25 (dd, 1H,
H-9'e), 4.32 (d, 1H, J1b, 2b =
7.7 Hz, H-1b), 4.45 (d, 1H, J1
a, 2a = 7.7 Hz, H-1a), 4.63 (d, 1)
H, J1d, 2d = 7.7 Hz, H-1d), 4.80
(M, 1H, H-4e), 4.86 (dd, 1H, J2
a, 3a = 9.1 Hz, H-2a), 4.90 (t, 1)
H, J2b, 3b = 7.7 Hz, H-2b), 5.12
(D, 1H, J5e, NH = 9.2 Hz, NH), 5.
14 (t, 1H, J3a, 4a = 9.2 Hz, H-3
a), 5.29 (dd, 1H, J6e, 7e = 4.3H)
z, J7e, 8e = 12.1 Hz, H-7e), 5.3
8 (t, 1H, J2d, 3d = 7.7 Hz, H-2
d), 5.71 (broad d, 1H, J3d, 4d
= 2.9 Hz, H-4d), 7.45-8.12 (m,
10H, 2Ph); Anal. Calcd for C83H110N2O
44Si (1867.9); C, 53.37%, H,
5.94%, N, 1.50%: Found; C, 53.
19%, H, 6.14%, N, 1.51%.

Example 7 O- (methyl 5-acetamide-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosiro Nate)
-(2 → 6) -O- (3-O-acetyl-2,4-di-
O-benzoyl-β-D-galactopyranosyl)-(1
→ 3) -O- (2-acetamido-4,6-di-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
(1 → 3) -O- (2,4,6-tri-O-acetyl-
β-D-galactopyranosyl)-(1 → 4) -2,3
6-tri-O-acetyl-β-D-glucopyranoside;
Synthesis of compound (18) A solution of compound (17) (329 mg, 0.18 mmol) in 2 ml of dichloromethane was added with 1.0 m of trifluoroacetic acid.
1 was added and reacted at room temperature for 2 hours. The reaction solution was concentrated and eluted with a developing solvent dichloromethane-methanol (30: 1) on a silica gel column (30 g) to obtain 240 mg (yield 77%) of compound (18) as an amorphous crystal. [Α] D + 26.0 ° (c1.0, chloroform); 1
1 H NMR (CDCl3) δ 1.85, 1.88 (2
s, 6H, 2AcN), 2.00-2.17 (13s,
39H, 13AcO), 3.30 (s, 3H, Me
O), 3.80 (t, 1H, J1a, 2a = J2a, 3
a = 6.4 Hz, H-2a), 4.31 (d, 1H, J
1b, 2b = 7.7 Hz, H-1b), 4.63 (d,
1H, J1d, 2d = 7.7 Hz, H-1d), 4.8
0 (m, 1H, H-4e), 5.12 (d, 1H, J5
e, NH = 8.1 Hz, NH), 5.14 (t, 1H,
J3a, 4a = 9.2 Hz, H-3a), 5.35.
(M, 1H, H-8e), 5.71 (broad d,
1H, J3d, 4d = 3.1 Hz, H-4d), 7.4
5-8.12 (m, 10H, 2Ph); Anal. Calcd for C78H98N2O4
4 (1767.6); C, 53.00%, H, 5.59.
%, N, 1.58%: Found; C, 52.79%,
H, 5.71%, N, 1.55%.

Example 8 O- (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosiro Nate)
-(2 → 6) -O- (3-O-acetyl-2,4-di-
O-benzoyl-β-D-galactopyranosyl)-(1
→ 3) -O- (2-acetamido-4,6-di-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
(1 → 3) -O- (2,4,6-tri-O-acetyl-
β-D-galactopyranosyl)-(1 → 4) -2,3
6-tri-O-acetyl-β-D-glucopyranosyl
Trichloroacetamidate; Synthesis of compound (19) A solution of compound (18) (212 mg, 0.12 mmol) and 0.35 ml of trichloroacetonitrile in 2 ml of dichloromethane was added with 1,8-diazabicyclo [5,4,4].
[0] Undec-7-ene (DBU; 18 mg) was added at 0 ° C, and the solution was stirred for 3 hours while keeping the solution at 0 ° C. After that, the reaction solution was concentrated, and the residue was applied to a silica gel column (30 g) as a developing solvent dichloromethane-methanol (3
Elution with 0: 1) gave 206 mg (90% yield) of compound (19) as amorphous crystals. [Α] D + 30.3 ° (c1.1, chloroform); 1
1 H NMR (CDCl3) δ 1.85, 1.88 (2
s, 6H, 2AcN), 2.00-2.17 (13s,
39H, 13AcO), 2.51 (dd, 1H, Jge
m = 13.2 Hz, J3e-eq, 4e = 4.6 Hz,
H-3e-eq), 3.29 (s, 3H, MeO),
4.12 (dd, 1H, Jgem = 12.5Hz, J8
e, 9e, = 2.4 Hz, H-9e), 4.25 (d
d, 1H, H-9'e), 4.35 (d, 1H, J1
b, 2b = 7.5 Hz, H-1b), 4.62 (d, 1)
H, J1d, 2d = 7.5 Hz, H-1d), 4.80
(M, 1H, H-4e), 4.92 (dd, 1H, J1
a, 2a = 4.0 Hz, J2a, 3a = 8.2 Hz, H
-2a), 5.12 (d, 1H, J5e, NH = 8.1
Hz, NH), 5.30 (dd, 1H, J6e, 7e =
3.5Hz, J7e, 8e = 10.2Hz, H-7
e), 5.38 (dd, 1H, J2d, 3d = 10.6)
Hz, H-2d), 5.71 (broad d, 1H,
J3d, 4d = 3.1 Hz, H-4d), 6.47.
(D, 1H, J1, 2 = 3.3 Hz, H-1a), 7.
46-8.11 (m, 10H, 2Ph); Anal. Calcd for C80H98N3O4
4Cl3 (1912.0); C, 50.25%, H,
5.17%, N, 2.20%: Found; C, 49.
95%, H, 5.31%, N, 2.09%.

Example 9 O- (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosiro Nate)
-(2 → 6) -O- (3-O-acetyl-2,4-di-
O-benzoyl-β-D-galactopyranosyl)-(1
→ 3) -O- (2-acetamido-4,6-di-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
(1 → 3) -O- (2,4,6-tri-O-acetyl-
β-D-galactopyranosyl)-(1 → 4)-(2,
3,6-Tri-O-acetyl-β-D-glucopyranosyl)-(1 → 1)-(2S, 3R, 4E) -2-azido-3-O-benzoyl-4-octadecene-1,3-diol ; Synthesis of Compound (26) 3 including Compound (25) (44 mg, 0.1 mmol) and Compound (19) (102 mg, 0.053 mmol)
Molecular Sieves 4A in ml of dichloromethane solution
(AW-300, 800 mg) was added, and the mixture was stirred at room temperature for 1 hr. Boron trifluoride etherate (0.04 ml) was added to this solution, the mixture was stirred at 0 ° C. for 8 hours, and the precipitated insoluble crystals were collected by filtration. After washing the crystals with dichloromethane, the washings were washed with a 1M sodium hydrogen carbonate solution and water, dried over anhydrous sodium sulfate and concentrated. This residue was purified using silica gel chromatography (30 g) by eluting with dichloromethane-methanol (50: 1) as a developing solvent to obtain 49.3 mg (43%) of compound (26) as an amorphous crystal.
Obtained. [Α] D + 4.3 ° (c0.9, chloroform); 1H
NMR (CDCl3) δ 0.88 (t, 3H, JM
e, CH2 = 6.6 Hz, MeCH2), 1.25
(S, 22H, 11CH2), 1.85, 1.88 (2
s, 6H, 2AcN), 2.00-2.11 (13s,
39H, 13AcO), 3.30 (s, 3H, Me
O), 4.31 (d, 1H, J1b, 2b = 8.1H)
z, H-1b), 4.49 (d, 1H, J1a, 2a =
7.3 Hz, H1a), 4.63 (d, 1H, J1d,
2d = 6.6 Hz, H-1d), 4.80 (m, 1H,
H-4e), 4.91 (t, 1H, J2b, 3b = 8.
2Hz, H-2b), 5.12 (d, 1H, J5e, N
H = 8.4 Hz, NH), 5.91 (m, 1H, H-
5; sphingosine), 7.42-8.11.
(M, 15H, 3Ph); Anal. Calcd for C103H135N5
O46 (2179.2); C, 56.77%, H, 6.
24%, N, 3.21%: Found; C, 56.51
%, H, 6.34%, N, 3.25%; IR (KBr) 3390 (NH), 2950,2870
(Me, methylene), 2110 (azid
o), 1750, 1230 (ester), 1680,
1540 (amido), 710 (Ph).

Example 10 O- (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonuropyranosiro Nate)
-(2 → 6) -O- (3-O-acetyl-2,4-di-
O-benzoyl-β-D-galactopyranosyl)-(1
→ 3) -O- (2-acetamido-4,6-di-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
(1 → 3) -O- (2,4,6-tri-O-acetyl-
β-D-galactopyranosyl)-(1 → 4)-(2
3,6-Tri-O-acetyl-β-D-glucopyranosyl)-(1 → 1)-(2S, 3R, 4E) -3-O-benzoyl-2-octadecaneamido-4-octadecene-1,3- Diol; Synthesis of compound (28) Aqueous solution of compound (26) (49 mg, 22 μmol) 83
Hydrogen sulfide was added in 6 ml of a 5% pyridine solution, and the mixture was mixed at 4 ° C at 0 ° C.
Reacted for 8 hours. This solution was concentrated and the residue [compound (2
7)] is octadecanoic acid (13 mg, 45 μ
mol) as a condensing agent, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC, 1
(3 mg, 70 μmol) and reacted in 1.5 ml of anhydrous dichloromethane at room temperature for 20 hours. After adding 20 ml of dichloromethane to this reaction solution and washing with water,
After drying over anhydrous sodium sulfate and concentrating, the residue was purified by eluting with a developing solvent, dichloromethane-methanol (30: 1), using silica gel column chromatography (20 g) to almost quantitatively amorphate compound (28). 54 as a crystal
mg was obtained. [Α] D + 8.6 ° (c1.3, chloroform); 1H
NMR (CDCl3) δ 0.88 (t, 3H, JM
e, CH2 = 6.4 Hz, MeCH2), 1.26
(S, 52H, 26CH2), 1.84, 1.88 (2
s, 6H, 2AcN), 1.94-2.16 (13s,
39H, 13AcO), 2.51 (dd, 1H, Jge
m = 13.2 Hz, J3e-eq, 4e = 4.4 Hz,
H-3e-eq), 3.31 (s, 3H, MeO),
4.28 (d, 1H, J1b, 2b = 7.9 Hz, H-
1b), 4.42 (d, 1H, J1a, 2a = 7.7H
z, H1a), 4.62 (d, 1H, J1d, 2d =
7.5 Hz, H-1d), 4.80 (m, 1H, H-4
e), 4.86 (t, 1H, J2a, 3a = 7.8H)
z, H-2a), 5.11 (d, 1H, J5e, NH =
9.4 Hz, NH), 5.44 (t, 1H, J2d, 3
d = 8.0 Hz, H-2d), 5.70 (broad)
d, 1H, J3d, 4d = 2.7 Hz, H-4d),
5.85 (m, 1H, H-5; sphingosine
e), 7.41-8.12 (m, 15H, 3Ph); Anal. Calcd for C121H171N3
O49 (2419.7); C, 60.06%, H, 7.
12%, N, 1.74%: Found; C, 59.81
%, H, 7.30%, N, 1.74%.

Example 11 O- (5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2 → 6) -O- (β- D-galactopyranosyl)-(1 → 3) -O- (2-acetamido-2-
Deoxy-β-D-glucopyranosyl)-(1 → 3)-
O- (β-D-galactopyranosyl)-(1 → 4)-
(Β-D-glucopyranosyl)-(1 → 1)-(2S,
3R, 4E) -3-O-Benzoyl-2-octadecanamide-4-octadecene-1,3-diol; Synthesis of compound (29) Sodium was added to 3 ml of a methanol solution containing compound (28) (54 mg, 21.8 μmol). Methoxide 10mg
Was added and the mixture was stirred at 0 ° C. for 24 hours. After that, 0.3m of water
1 was added, and the mixture was stirred at room temperature for 16 hours. The solution was neutralized with Amberlite IR-120 (H +) ion exchange resin, and the resin was washed with dichloromethane-methanol-water (50: 40: 7) to extract the desired product and concentrate it. This concentrated residue was collected on Sephadex LH-20 (30
Purification by column chromatography using g) with the same solvent as above gave 29 mg (yield 83%) of the desired compound (29) as amorphous crystals. [Α] D-5.2 ° (c0.6, 1: 1: 0.2 = dichloromethane: methanol: water); 1H NMR (92:
2 = (CD3) 2SO-D2O) δ 1.82, 1.8
8 (2s, 6H, 2AcN), 2.64 (broad
dd, 1H, H-3e-eq), 4.17 (2d, 2
H, J1a, 2a = J1d, 2d = 8.1 Hz, H1
a, H-1d), 4.28 (d, 1H, J1b, 2b =
7.1 Hz, H-1b), 4.79 (d, 1H, J1
c, 2c = 8.0 Hz, H-1c); ceramide
unit δ 0.85 (2t, 6H, 2MeCH
2), 1.24 (s, 50H, 25CH2), 1.45
(M, 2H, COCH2CH2), 2.03 (t, 2
H, COCH2), 5.36 (dd, 1H, J3, 4 =
7.1 Hz, J = 15.2 Hz, H-4), 5.54
(M, 1HJ5,6 = J5,6 '= 6.6Hz, H-
5); Anal. Calcd for C73H131N3O
31 (1546.8); C, 56.68%, H, 8.5.
4%, N, 2.72%: Found; C, 56.41
%, H, 8.66%, N, 2.59%.

Example 12 Sialyl (α2-6) lactotetraosylceramide (2
Measurement of binding activity of 9) to influenza virus) 1: Experimental materials and methods Influenza virus A / PR / 8/34 (H1N)
1), influenza virus B / Lee / 40, influenza virus C / AnnArbor / 1/50, type A, type B, and type C, respectively. For A type and B type,
After transplanting into the chorioallantoic cavity of the hatched chicken eggs on the 10th day, culturing at 34 ° C. for 2 days, and leaving at 4 ° C. overnight, the chorioallantoic fluid containing the virus was subjected to fractional centrifugation at 15000 rpm for 60 minutes,
The pellet was suspended in a phosphate buffer solution (abbreviated as PBS) containing 9% sodium chloride, and from the bottom, 60% sucrose-PBS solution,
A 30% sucrose-PBS solution and a virus-PBS solution were overlaid in this order and purified by discontinuous sucrose density gradient centrifugation at 22000 rpm for 90 minutes. For C type, 8
100 μl of a 5000-fold diluted virus solution was transplanted into the amniotic cavity of the hatched chicken eggs on the day 1 and cultured at 34 ° C. for 3 days, and then 4
Amniotic fluid containing the virus, which was obtained by leaving it overnight at ℃, 150
Separately centrifuge at 00 rpm for 60 minutes, suspend the pellet in PBS, overlay 60% sucrose-PBS solution, 30% sucrose-PBS solution, virus-PBS solution in that order from the bottom, and discontinue centrifugation at 22000 rpm for 90 minutes. Purified by sugar density gradient centrifugation.

2: Antibody Influenza virus A / PR / 8/34 (H1N
The anti-A type rabbit polyclonal serum against 1) and the anti-type B rabbit polyclonal serum against influenza virus B / Lee / 40 were each influenza virus 1000 HAU suspended in 1 ml of PBS, and then subcutaneously injected into a rabbit (Japanese white), Ten days later, the same amount was intraperitoneally administered as a booster, and four days later, whole blood was collected and treated by a conventional method to obtain antiserum. Anti-C against influenza virus C / Ann Arbor / 1/50
As the rabbit rabbit serum, one provided by Dr. Kiyoto Nakayama of Yamagata University School of Medicine was used. Each of these sera had P
It was diluted 2000 times, 1,000 times, and 500 times with BS before use.

3: Used gangliosides and their structures

[Table 1] To list.

4: Method for measuring virus-binding activity Silica gel thin layer plates (Polygram Sil G, M)
Archery Nsgel), spot an appropriate amount of sample, develop with chloroform / methanol / 12 mM magnesium chloride aqueous solution (5: 4: 1) (V / V), air-dry, then 1% ovalbumin, 1% polyvinylpyrrolidone , 0.02% sodium azide-containing PBS solution (Solution A) was gradually dipped for blocking. P
After washing 5 times with BS, HAU (hemagglutination activity: microplate (96U-bottomwells, Falc
on) and the purified influenza virus to
Dilute twice with a 01% gelatin-PBS solution and add to it 0.
Add 5% (V / V) chicken red blood cells-PBS suspension,
The reaction was carried out at 4 ° C for 1 hour. HAU was expressed as the highest dilution of virus required for chicken red blood cells to aggregate. ) 2 ^{6-2 8} of influenza virus -PBS
Shake in suspension at 4 ° C. overnight at 120 rpm. This was washed 5 times with PBS and then blocked with Solution A for 30 minutes at room temperature. After washing 3 times with PBS, it was shaken in a 3% polyvinylpyrrolidone-PBS solution of an anti-virus antibody (solution B) at 4 ° C. and 120 rpm for 2 hours. This was washed 5 times with PBS and blocked with solution A for 30 minutes at room temperature. After this, PB
Washed 3 times with S and labeled with horseradish peroxidase anti-rabbit immunoglobulin antibody (manufactured by Seikagaku Corporation) or Protein A (Organon Tek).
nika Corp. Lot No. 3353
0) in Solution B solution (each 1000
2 times, 500 times dilution) and shaken at 4 ° C. and 120 rpm for 2 hours. After washing the thin plate 5 times with PBS,
M Tris-hydrochloric acid buffer solution (pH 7.2) /0.3% 4-chloro-1-naphthol methanol solution / 31% hydrogen peroxide solution (5: 1: 0.02) (V / V) was added, 1 at 4 ° C
Shake for 5 minutes. This was washed with distilled water and air-dried, and the color development was quantified with a densitometer (CS-910 manufactured by Shimadzu Corporation) at a measurement wavelength of 578 nm and a control wavelength of 780 nm.

As a result, FIG. 1 (in the figure, ● indicates IV ⁶ (NeuAc)
Lc4Cer, ○ indicates IV ⁶ (NeuAc) nLc4Cer, ▲ indicates GM3 (NeuGc),
■ indicates GM1b (NeuAc), △ indicates GT1b (NeuAc), IV ⁴ (NeuAc) nLc4
Cer, IV ³ (NeuGc) nLc4Cer, IV ³ (NeuAc) Lc4Cer, GM3
(NeuAc), GD3 (NeuAc), GM1a (NeuAc), and GD1a (NeuAc) are shown; each abbreviation is listed in Table 1 above), and the binding activity of various gangliosides to influenza virus B / Lee / 40 is shown in As shown, IV in the present invention
⁶ NeuAc α2-6Galβ1-3GlcNA abbreviated as (NeuAc) Lc4Cer
sialyl represented by c β1-3Gal β1-4Glc β1-Cer (α2
-6) It was found that lactotetraosylceramide had extremely strong binding properties with respect to this influenza virus type B as compared with other gangliosides.

The sialyl (α2-6) lactotetraosylceramide of the present invention is influenza virus A /
PR / 8/34 (H1N1) also had a similar strong binding property. Furthermore, the sialyl (α2-6) lactotetraosylceramide of the present invention was not found to bind to the influenza virus C / AnnArbor / 1/50.

Furthermore, from the above results, it is found that the sialyl (α2-6) lactotetraosylceramide of the present invention binds to influenza virus A and B type HA (hemagglutinin) very effectively. found. Further, from this, the sialyl (α2- of the present invention is
6) Use of lactotetraosylceramide for effective removal of the virus in a sample infected with influenza virus type A or type B having HA in the viral membrane, and for injection with prevention of viral infection A sample such as a preparation or a test sample can be easily prepared, and in addition, it can be used for preparing an antibody using the present compound as an antigen.

Example 3 1 g of silica gel G (manufactured by Sigma) was placed in a 50 ml round-bottomed flask, and 1 mg of sialyl (α2-6) lactotetraosylceramide of the present invention dissolved in 1 ml of chloroform was added thereto. Then, this was evaporated to dryness with a rotary evaporator, and then PBS containing 20% human serum albumin and 1% polyvinylpyrrolidone (pH
6.8) 5 ml was added, mixed well and blocked. This silica gel was washed 5 times with 20 ml PBS, and then filled in a glass tube for chromatography having a diameter of 0.5 cm while being suspended in PBS. 1.0 ml of a PBS solution containing influenza virus A / PR / 8/34 (H1N1) having a HAU of 2 ¹² was passed through this and washed twice with PBS. At this time, HAU activity was detected for the virus in the passage solution and the washing solution, but the virus was not detected, and a passing solution or washing solution containing no virus was obtained, and the virus was adsorbed to the column. It was confirmed that it was done.

Example 4 To a silica gel column chromatography prepared by the method described in Example 3, 1.0 ml of a PBS solution of influenza virus B / Lee / 40 having HAU of 2 ¹² was added and passed through with human serum. The virus was measured in the serum that passed through the column, but the virus was not detected, and it was possible to obtain a virus-free serum, which also indicates that the virus can be removed from human serum. Was confirmed.

【The invention's effect】

The present invention provides and polishes a sialyl (α2-6) lactotetraosylceramide represented by the novel formula NeuAcα2-6Galβ1-3GlcNAc β1-3Galβ1-4Glcβ1-Cer. (Α
2-6) Using lactotetraosylceramide, effective removal of the virus in a sample infected with influenza virus type A or type B having HA on the viral membrane can be achieved, and viral infection was prevented. Samples such as injectable preparations and test samples can be easily prepared, and in addition, useful compounds that can be used for preparing an antibody using the present compound as an antigen are provided.

[Brief description of drawings]

FIG. 1 is a diagram showing measurement of binding activity for influenza virus B / Lee / 40 by various gangliosides containing sialyl (α2-6) lactotetraosylceramide of the present invention.

Claims (1)

[Claims] 1. The following formula: NeuAcα2-6Galβ1-3GlcNAc β1-3Galβ1-4Glcβ1-Cer (wherein NeuAc is an N-acetylneuraminic acid residue,
Gal is a galactose residue, GlcNAc is an N-acetylglucosamine residue, Glc is a glucose residue, and Cer is a ceramide group.) Sialyl (α2-6) lactotetraosylceramide.