JPH0399091A - Lactosylceramide derivative and its production - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [A represents formula II ((m) is 10-14; R<2> represents H or 16-24C fatty acid residue optionally having R<1>O-group); R<1> represents OH-protecting group]. EXAMPLE:Benzylated lactosylceramide. USE:An intermediate for producing various sphingoglycoplipid derivatives. PREPARATION:A sialoglycolipid derivative expressed by formula III [B represents (substituted)sialic acid residue] is hydrolyzed preferably in the presence of a heteropolyacid catalyst (example; phosphotungstic acid or phosphomolybdic acid).

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel lactosylceramide derivative useful as an intermediate in the production of various glycosphingolipid derivatives and a method for producing the same.

[Prior Art and Problems to be Solved by the Invention] It is generally known that glycosphingolipids perform various important functions on the surface layer of animal cells. For example, it is known to be involved in cell nllJ RE recognition, receptors for bacterial hormones and toxins, immune functions, etc. [see, for example, J.N. κanfar and S.
Hakomori, “Handbook of L
ipidResearch″. 3, Sphin
golipid Biochemistry. Ple
num Press, New York (1983
)) In order to elucidate these functions and create new medicines, it is necessary to produce these glycosphingolipids in large quantities.

By the way, although it is possible to extract and isolate glycosphingolipids from naturally occurring animal cells, large quantities of animal cells are required for mass production, and there are limits to this in terms of yield, cost, etc. be. Therefore, chemical combinations of glycosphingolipids are being investigated.

However, the conventional synthesis method of glycosphingolipids involves binding sphingolipids to glycosylamines, but this synthesis method is extremely difficult and has poor yields (Ca
rbohydrate Research, 155 (
1986) CI-C5; 156 (1986) Cl
~C5; 162 (i986) 237-246].

Therefore, the development of an efficient chemical synthesis method for glycosphingolipids and a production intermediate that can be used therefor has been eagerly awaited.

[Means to solve the problem]

Under these circumstances, the present inventors have conducted extensive research to solve the above problems, and have found that by cleaving a naturally occurring oligosaccharide bound to a sphingolipid at a specific position, an intermediate for producing glycosphingolipids can be obtained. The present invention was completed based on the discovery that sphingocarbohydrates can be synthesized efficiently using this method.

That is, the present invention provides the following general formula (I) useful as an intermediate for the production of glycosphingolipids [wherein A is a group (here, m represents a number of 10 to 14, R2 is a hydrogen atom or a substituent R 16 to 24 carbon atoms, which may have 0-
The present invention provides a lactosylceramide derivative represented by the following formula (representing a fatty acid residue), and Rl represents a hydroxyl group-protecting group, and a method for producing the same.

In the lactosylceramide derivative (1) of the present invention, the protecting group for the hydroxyl group represented by R' in the general formula (I) is not particularly limited as long as it is a group normally used as a protecting group for the hydroxyl group of sugars, but substituted Examples include an aralkyl group which may have a group, an acyl group, an alkoxycarbonyl group, an alkoxycarbonylalkyl group, an alkyl group which may have a substituent. Examples of the aralkyl group include 2-3- or 4-hydroxybenzyl, benzyl, 2-(3,4-dihydroxyphenyl)
Ethyl, 1-(3.4-dihydroxyphenyl)ethyl, 1-(3.4-dihydroxyphenyl)ethyl, 2-
(3-hydroxyphenyl)ethyl, 3-(4-hydroxyphenyl)propyl, 6-(3.4-hydroxyphenyl)hexyl, 3'. 4-dihydroxybenzyl, 3.4.5-trihydroxybenzyl, 2-formyloxybenzyl, 3-acetyloxybenzyl, 3-(2-acetylkiosyphenyl>probyl, 4-(4-acetyloxyphenyl) Butyl, 2-propionyloxybenzyl, 3-(3-butyryloxyphenyl)propyl, 4-(4-isobutyryloxyphenyl)butyl, 5-(2-tert-
butylcarbonyloxyphenyl)bentyl, 6-〈3
-pentanoyloxyphenyl〉hexyl, (2.4-
Examples include phenylalkyl groups which may have a straight or branched alkyl group having 1 to 6 carbon atoms as a substituent on the phenyl nucleus such as diacetyloxy)benzyl. Acyl groups include formyl, acetyl, propionyl, butyryl, pentanoyl, hexanoyl, etc. having 1 to 6 carbon atoms.
Direct or branched alkanoyl group; benzoyl, 2-3
- or 4-methoxybenzoyl, 2-3- or 4-ethoxybenzoyl, 4-isoproboxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3.4-dimethoxybenzoyl, 3.4
- 1 to 2 linear or branched alkoxy groups having 1 to 6 carbon atoms on the phenyl nucleus such as diethoxybenzoyl, 2.5-dimethoxybenzoyl, 2.6-dimethoxybenzoyl group, etc.
Examples include benzoyl groups that may be present.

As the alkoxycarbonyl group, methoxycarbonyl,
Ethoxycarbonyl, isoproboxycarbonyl, n-
butoxycarbonyl, tert-butoxycarbonyl,
Examples include straight or branched alkoxycarbonyl groups having 1 to 6 carbon atoms, such as benzyloxycarbonyl and hexyloxycarbonyl groups.

Examples of alkoxycarbonylalkyl groups include methoxycarbonylmethyl, 3-methoxycarbonylbrobyl, 4-
Ethoxycarbonylbutyl, 6-proboxycarbonylhexyl, 5-improboxycarbonylpentyl, l
．． 1-dimethyl-2-butoxylponylethyl, 2-
Methyl-3-tert-butoxycarbonylprobyl,
The alkoxy moiety of 2-pentyloxycarbonylethyl, hexyloxycarbonylethyl group, etc. has 1 to 6 carbon atoms.
Examples include straight or branched chain alkyl alkoxycarbonyl alkyl groups. Examples of the alkyl group which may have a substituent include a methyl group, an ethyl group, an allyl group, and a methoxyethoxymethyl group. 16-24 carbon atoms which may have a substituent R'O- represented by R2
Examples of the fatty acid residue include a palmitoyl group, a heptadecyloyl group, a stearoyl group, a nonadecanoyl group, an arachinoyl group, a behenoyl group, a lignocerinoyl group, and a group in which R'0- is substituted at the α position of these groups.

The lactosylceramide derivative (I) of the present invention is produced, for example, according to the following reaction formula.

(I) [In the formula, B represents a sialic acid residue which may have a substituent, and A and R1 have the same meanings as above] That is, a sialoglycolipid derivative represented by the general formula (n) The lactosylceramide derivative of the present invention is produced by hydrolyzing and selectively removing sialic acid residues that may have substituents.

The sialoglycolipid derivative (n), which is a raw material, is obtained by protecting the hydroxyl groups of sialoglycolipids derived from various animals. Examples of sialoglycolipids include ganglioside GM. , G.O. etc., but those having one sialic acid are preferred from the viewpoint of yield etc. Among them, NG hematoside is particularly preferred from the viewpoint of easy availability. Furthermore, the hydroxyl groups of these sialoglycolipids can be protected by means known per se. For example, when protecting with an aralkyl group, dissolve the sialoglycolipid in an appropriate solvent,
Aralkyl chloride, in the presence of a base such as sodium hydride, pyridine, sodium hydroxide, potassium hydroxide, etc.
An aralkyl halide such as aralkyl bromide may be reacted. In addition, when protecting with an acyl group, the sialoglycolipid is dissolved in a suitable solvent and reacted with an acylating agent such as an acid noolide or an acid anhydride in the presence of a base such as pyridine, triethylamine, or dimethylaniline. Bye. Solvents used in these hydroxyl group protection reactions include ethers such as dioxane, diethylene glycol dimethyl ether, diethyl ether, and tetrahydrofuran; aromatic hydrocarbons such as benzene, toluene, and xylone; dimethylformamide, dimethyl sulfoxide, and hexamethyl phosphate triamide. Examples include polar solvents such as. After completion of the hydroxyl group protection reaction, the hydroxyl group protected sialoglycolipid can be isolated and purified from the reaction mixture by a method known per se. For example, it can be neutralized with an acid, extracted with a suitable solvent such as methylene chloride, and purified using silica gel force column chromatography, gel filtration, or the like.

The hydrolysis reaction of the sialoglycolipid derivative (II) thus obtained can be carried out under conditions that allow selective removal of only the sialic acid residue optionally having a substituent represented by (b) in formula (n). Although not limited, it is preferred to hydrolyze the sialoglycolipid derivative (II) in a suitable solvent in the presence of a heteroboric acid catalyst.

Examples of the heteroboric acid catalyst used include phosphotungstic acid and phosphomolybdic acid, and these may be used alone or in combination of two or more. Examples of the reaction solvent used include various organic acids, inorganic acids, or a mixture of both. Examples of the organic acids include acetic acid and triple olacetic acid, and examples of the inorganic acids include hydrochloric acid and sulfuric acid. The concentration of these organic acids and inorganic acids is, for example, about 95% by weight in the case of acetic acid, and 0.5% by weight in the case of hydrochloric acid. In the case of a mixed solvent of acetic acid and hydrochloric acid, it is preferably about 80% by weight of acetic acid and about IN of hydrochloric acid. The reaction temperature is 50-110°C, especially 50-70°C.
℃ is preferable, and the reaction time is 30 minutes or more, especially 10 to 15
time is preferable.

After completion of the reaction, the lactosylceramide derivative (I) of the present invention can be isolated and purified from the reaction product by means known per se, such as various column chromatography.

〔Effect of the invention〕

The lactosylceramide derivative (I) of the present invention is useful as an intermediate for producing various glycosphingolipids that are difficult to handle.

That is, glycosphingolipids known as globo, isoglobo, lacto, neolacto, and ganglio glycosphingolipids commonly contain the lactosylceramide moiety of the compound of the present invention. Therefore, when attempting to synthesize such naturally occurring and non-naturally occurring glycosphingolipids, it is possible to efficiently combine the free hydroxyl group of the compound of the present invention by dehydrating the reducing end of an appropriate oligosaccharide derivative and the free hydroxyl group of the present compound. You can achieve your goals well. For example, the following sugar chain structure Puca
I→2 Galβ1 = 4 G1cNAc3 ↑ If Fucα1 and the compound (1) of the present invention are subjected to dehydration condensation and then the hydroxyl protecting group is removed, natural and/or non-natural L
e' glycolipids can be obtained.

〔Example〕

Next, the present invention will be explained in detail with reference to Examples.

Reference Example 1 Isolation of NG hematoside from horse red blood cell membrane Horse blood (
Jama meat treatment plant
) 1 5 1, add 3% glacial acetic acid lO to 1.51
centrifuged (10,000 rpm, 2
0 minutes> and then subjected to continuous centrifugation under the same conditions to obtain a horse red blood cell membrane fraction of 0.31. This was repeated 10 times to obtain a total of 31 horse red blood cell membrane fractions. The obtained horse red blood cell membrane fraction was homogenized in 95% ethanol SIl for 5 minutes, and 181 g of 95% ethanol was added thereto. This was treated at 80°C for 15 minutes.

This was further filtered through a warmed Buchner funnel.

This extraction process was repeated on the resulting precipitate. The obtained filtrate was evaporated using a rotary evaporator for 40 minutes.
The solvent was distilled off at °C. This was dissolved in a solvent of 1,51 chloroform:methanol=2:l. This was filtered again and concentrated. As a result, 63 g of lipid fraction was obtained. 63 g of the obtained lipid fraction was added to 140 g of pyridine.
d, and then add 100 rd of acetic anhydride to this.
was added and left overnight at room temperature. Toluene was added as an azeotrope, and the solvent was distilled off until the odor of pyridine disappeared. As a result, a crude acetylated glycolipid fraction containing acetylated glycolipids, phospholipids, cholesterol, and the like was obtained.

The obtained crude acetylated glycolipid fraction was subjected to Florisil column chromatography. Here, Florisil 500g
column (with 1,2-dichloroethane (OCR))
d=5 cm). Cholesterol and other neutral lipids were eluted with DCB, and the acetylated glycolipid fraction was eluted with dichloroethane:acetone=1:1. The eluate was concentrated and acetyl NG-hematoside [Ac-NG-
tlam) (TLC Rf: 0.67, kuoo
20.15 g of an acetylated glycolipid fraction containing form:methanol (C/M) = 9:1) was obtained. This acetylated glycolipid fraction9. 09g to 100mji of chloroform-methanol mixture (2:1)! and 0.5% sodium methoxide in methanol.
〇1 was added (p}I about 10), and this was left at room temperature for 30 minutes. This was mixed with ion exchange resin IR^-120B (H
(Organo), filtered through a filter, and concentrated under reduced pressure to obtain 5.04 g of a glycolipid fraction. This was dissolved in water, dialyzed against water at 4°C, and then freeze-dried. , NG-hematoside 1.60g [TLC Rf: 0.42 (
Solvent, chloroform:methanol=9:1)] was obtained.

Reference Example 2 Benzylation of NG Hematoside 200 mg of the purified NG hematoside obtained in Reference Example 1 was dissolved in dioxane 14- and 4.0 g of potassium hydroxide, and reacted at 60°C for 30 minutes.

After the reaction, benzyl bromide 8- was added and stirred at 60°C overnight. After stirring, an appropriate amount of distilled water was added to the mixture, and the mixture was neutralized with IN hydrochloric acid. This reaction solution was subjected to solvent extraction with chloroform, washed twice with water, and filtered.

After concentration under reduced pressure, this was applied to a Sephadex Ll{-20 column (
22φ×1500 mm) and eluted with chloroform/methanol (C/M) = 2/1 to obtain 280 μm of benzylated NG hematoside.

'11-NMR spectrum (JNM GSX-500 CDfJ s/TMS) δ
:0.78~0. 96 (R-CHa)0.96-1
．． 37 (R-CH.-R”)1.67(dd, N
GNA-3ax, Jsax. s*q=12.8}1z
, J. ．． ．． , 4=11. 4) 1. 92-2. 08 (Car-6, Cer-
3゜a)2. 25-2. 35 (Car-3' b
) 2.40 (dd, NGNA-3eq. J3s
q+i = 11.6) 3.03(ddd, NGN
A.I. J4. s=10.9)3. 1! ll~3.
43 (Cer-2', Glc-5.Gal
-2, Gal-5, Gal-6a, ring-H) 3.43 to 3.63 (Glc-2. Gal-3,
Gal-6b, ring-H)3. 45 (G
al-3. J=3. 2) 3.63-4.05 (
NGAN-5. Glc-6a, Car-3.
Glc-3. Glc-6b, Glc-4. G
al-4, ring-H)3. 99 (Gal-
4. J=3. 2) 4.05-5.42 (Car
-2. 0al-1. Glc-1. NGN^
-6, Cer-4, ring-H, benzy
l-41) 4.26 (Gal-1. J=7.8) 4
J2 (Glc-1, J=7.8)5. 46-5.
56 (Car-5)5. 72-5. 82 (C
ar-1)6. 8-7. 6 (aromatic-H
) Example 1 Production of benzylated lactosylceramide Pensylated NG hematoside obtained in Reference Example 2
Q Q mg (0.04 mmol) to 201n
1 of 95% acetic acid. To this was added 80 mg of phosphotungstic acid (manufactured by Junsei Chemical Co., Ltd.), and the mixture was stirred at 60° C. for 17 hours to react. After reaction, methylene chloride 500ml
! and washed twice with IN sodium hydroxide and distilled water. After extraction and washing, concentrate under reduced pressure and perform preparative TLC.
Purification was performed by (PTLC) to obtain 23.7 mg of benzylated lactosylceramide.

Rf: 0,48 (solvent, toluene: ethyl acetate = 1:1
)' H-NMR spectrum (JNM GSX-500 CDC1s/TMS) δ:
0.82~0. 92 (R-CL) 1.05-1. 38 (R-Cll.-R')1.
38-1. 47 (Cer-4')1. 71~
1. 91 (Cer-3°)1. 92-2. 10
(Cer-6) 3.18-3.40 (Gal-5.
Glc-5. Gal-2)3. 36 (Gal
-2. J=10. 9Hz) 3.40-3.62
(Gal-3, Glc-3, Gal-6a, Gl
c-2)3. 47 (Gal-3, J= 3.
4) 3.5HG1c-3, J=11.4)3. 5
5 (Glc-2, J= 10.4) 3.62~
4.20 (Glc-6a, Gal-4. Gal-6
b, Cer-3, Glc-6b. Glc-4,
Car-2) 3.69 (Glc-6a, J=16.
1)3. 76 (Gal-4) 3. 87 (Glc-6b) 3.99 (Glc-4. J-9.8) 4.20-5
．． 20 (Gal-1, Glc-1, benzyl-
}1)4. 28 (Gal-1. J= 10.5
)4.31 (Glc-1, J=7.6)5.20~5
．． 42 (Cer-4.benzyl-tl)5. 4
5-5. 56 (Cer-5)5. 63-5. 8
0 (Cer-1) 6.8-7.6 (aromatic
-41) Voluntary amendment to the above procedures> 1999 Patent Application No. 238065 2. Name of the invention Lactosylceramide derivative and method for producing the same 3. Relationship with the case of the person making the amendment Applicant name: Japan Antibody Research Institute, Inc. 4. Agent address: 1-3-6, Nihonbashi Ningyocho, Chuo-ku, Tokyo (postal address:
103> Target of correction "Reference example 3 Contents of format correction (1) In the specification, rJamaJ on the bottom line of page 13 is corrected to rTama."

(2) Lines 1 to 3 of page 14 of the same book, ``Centrifuge this to separate both horse red blood cell membranes.''"Fraction" is corrected.

(3) Page 17, line 4 r J3. q. 4=11. 6J and aru J3
-4. Correct it as 4 = 4, IJ.

(4) Page 17, line 10 r NGAN-5J r　Corrected as NGNA-54.

(5) Page 19, line 18, r6.8-7.6 (aromatic-H) Change the line after J and insert the following sentence.

? The same operation as in Example 1 was carried out, and the acetylated glycolipid fraction 2 containing acetyl NG-hematoside obtained in the process was
9.1 g was transferred to a Wakogel C-300 column (75φX
140++o++) and benzene/a7ton (B/
Acetylglucobylanose was eluted with A) = 9:1 and then benzene/acetone (B/A) = 4:1. Acetyl NG-hematoside 11.35
I got g.

'}I-NMR spectrum (AM-400 CDI!3/TMS) δ: 0. 82
-0. 92 (m, R-CH3)1. 05-1.
45 (m, R-CI42-R')1. 88
(dd, NGNA-3ax, Jsax, *q=13
．． 5}1z, J, ■. 4=11. 1) 1. 95-2. 38 (ill. COCHj.
Car-6) 2.46 (dd, NGNA-3eq.
Js-q, ,=5. 4)3. 51-3. 58
(m, Cer-1a)3. 70 (ddd, G
lc-5+ Ja. s=IO. 3. Js. 6m
=4. 3, J5+. =1. 9) 3. 74 (dd, NGNAJ, Js, s=1
0.5. Js. t=4. 5)3. 87-3.
99 (m, Cer-1b, Gal-5)3. 93
(dd, Glc-4. Js. 4=9.7)3
．． 96 (dd, Gal-3. Jt, s=10
．． 8, Js. 4:3. 2)4. 04-4.
20 (m, Ga 1-6a, -6b, NGNA
-5, NGNA-9a)4. 23-4. 36 (
m, NGN^-9b. Cer-2, Ac[lC}
lzcON}la)4. 40 (dd, Glc-6
a, Jsa, gb"ll. 4) 4.48 (d.G
1c-1,J,,z=7.8)4. 54(dd, G
lc-6b) 4.56 (cl, Gal-1, J+, z=7, 7)4.
61 ((1. AcOCllzC()N}lb, c, b=x5. 4) 4.74 (dd, Gal-2) 4. 87 (dd, Gl(:-2. J2. 3=
9. 3>5.12 (ddd,NGN8-8.J,a
=6.6. Js. I=3.1)5. 19-5. 29
(m, Cer-3, G 1 c-3.NGN^
-7)5. 30-5. 40 (+n, Cer-4
)5. 45 (dd, Gal-4. Ja. s:
+1. 3)5. 49 (ddt!, NGNA-4
, J. , s=t0. 9)5. 65 (d, C
ar-N}! ．． ．． b, ms=9. 1)5. ? 7
(01, Cer-5) 6. 07 (d, NGNA-NH. Js, mm
:10. 1) Reference Example 4 Synthesis of benzoylated NG hematoside 1.00 g of the acetyl NG hematoside obtained in Reference Example 3 was mixed with chloroform-methanol mixture (2:1) 60 mt
100 μm of sodium methoxide was added, and the mixture was stirred at room temperature for 30 minutes. After neutralizing this with acidic ion exchange resin IR8-120B, the same resin was further added to make it acidic and the mixture was stirred at room temperature overnight. After removing the resin with a filter, it was concentrated under reduced pressure to obtain 50mj of pyridine! was added to dissolve the residue.

This was brought to 0°C in an ice water bath, and 5 mg of penzoyl chloride was added.
was added dropwise, the temperature was returned to room temperature, and the reaction was allowed to proceed overnight. The mixture was concentrated under reduced pressure at 40° C. or lower using a rotary pump, and the residue was extracted with chloroform, washed with an aqueous sodium bicarbonate solution, and dried over anhydrous magnesium sulfate. After removing the insoluble matter by filtration, it was concentrated under reduced pressure, and the residue was passed through a Wakogel C-300 column (
37φX275a+m) and benzene/acetone (
B/A)=50:1 was used for elution. Benzoyl N
1.11 g of G-hematoside was obtained.

'H-NMR spectrum (AM-400 CDCl3/TMS) δ: 0. 75
-0. 91 (m. R-CHa)0. 9}4. 3
8 (m. R-CL-R')1. 72 (dd,
NGNA-3ax. Jlam+s+eq=12.
5t{z. J3. ．． ．． ．． =11. 5) 1. 97-2. 05 (m. Car-6)2.
56 (dd, NGNA-3eq. Jsa14=4
．． 9)3. 37 (8, COOCH3) 3. 45 (dd, Gal-6a, Js, 1a
"3, a, Jean gb"ll. 3)3. 5
6 (dd, Ga 1-6b. J5, @b=6.
9)3. 59-3. 65(m, Glc-5)3
．． 80-3. 88 (m, Ga I-5)3.
91 (ddd. NGN^-5. J.. s”IO
．． 5, JS. s=10. 3, Js, question=9.
8) 4.14 (dd,NGNA-6,J@,?=2.7)
4. 23 (dd, Glc-4. Js. <=9
．． 5, J4. s=9. 5)4. 27-4.
50 (m, Glc-6a.-6b, BzOCH
zCON}la, NGNA-9a) 4. 63 (d. BzOCH2CONl{b, J
-, -=15. 2}4. 78 (d. Glc{
, J+, t=7. 9)4. 90 (dd, G
at-3. J2,=10. 1. ．． L. 4=3.
0) 5.00 (d. Gal-1. Jl+ 2=
8. 0>5. 11 (d, Gal-4) 5. 16 (dd, NGNA-9b, Js. s
b=2. 5, J Ha, sb42. 8)5. 25
(NGNA-4) 5. 27-5. 41 (m, Cer-2, -3
)5. 42 (dd, Glc-2. Jz. s”
9. 7>5. 50 (dd, Ga 1-2>5.
70 (dd, Glc-3) 5. 80-6, 00 (m, Cer-4, -5,
-NH, NGNA-7)6. 09 (d, NG
NA-NH)6. 17 (ddd, NGN^-8.
J=. s-=4. 3)6. 8-8. 4(+n
, aromatic-H) Example 2 Production method of benzoylated lactosylceramide 100 mg of benzoyl NG hematoside obtained in Reference Example 4 was added to 100 mj!
of 95% acetic acid. To this was added 500 mg of phosphotungstic acid, and the mixture was stirred at 80° C. for 15 hours to react. Concentrate under reduced pressure at 40°C or less using a rotary pump,
The residue was extracted with chloroform, washed with an aqueous sodium bicarbonate solution, and then dried over anhydrous magnesium sulfate. After filtering off insoluble matters, the residue was concentrated under reduced pressure, and the residue was applied to a Wakogel C-300 column (18φ x 165111 [+1)] and eluted using benzene/a7ton (B/A)=9=1. The eluate was concentrated under reduced pressure and purified by preparative TLC to obtain 24.7 µ of benzoylated lactosylceramide.

’}I-NMR spectrum

Claims (1)

[Claims] 1. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, A is a group ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (Here, m is 10 to 14, and R^2 is a hydrogen atom or a carbon number of 16 to 16 which may have a substituent R^1O-
24 fatty acid residue), and R^1 represents a hydroxyl group protecting group.] A lactosylceramide derivative represented by: 2. General formula (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) [In the formula, A is a group ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (Here, m indicates a number from 10 to 14, R^2 is a hydrogen atom or a carbon number of 16-16 which may have a substituent R^1O-
24 fatty acid residue), B indicates a sialic acid residue which may have a substituent, and R^1 indicates a hydroxyl group protecting group. 2. The method for producing a lactosylceramide derivative according to claim 1.