JPH03101691A - Gangliosides and intermediate therefor - Google Patents

Abstract

NEW MATERIAL:Compounds expressed by formulas I to V (R is aliphatic acyl; R<1> is H or lower alkyl; R<2> to R<5> are equally H or independently acyl; R<6> is N3, NH2, etc.; (n) is 0-20, provided that R<2> to R<5> are H when R<1> is H and acyl when R<1> is lower alkyl; R<7> is NHCOCH3, etc.; R<8> is 1-30C alkyl or benzyloxy, provided that R<2> to R<5> are acyl when R<8> is benzyloxy). USE:A medicine for senility or carcinostatic agent. PREPARATION:A 2-alpha-O-glycoside compound is used as a starting material and reacted in a nonpolar solvent, such as BF3-ether, at 0 deg.C to ambient temperature and the resultant compound is then reacted with trichloroacetonitrile in a solvent, such as dichloromethane. The obtained compound is subsequently reacted with an azidosphingosine derivative expressed by formula VI in the presence of a Lewis acid in a nonpolar solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Application of the Invention] The present invention relates to novel gangliosides and synthetic intermediates thereof, which are expected to have utility as anti-inflammatory agents and anticancer agents.

[Background of the Invention Coganglioside is a general term for sphingosaccharide ffI having sialic acid, and due to differences in its structure, especially the sugar chain structure, for example, GM 1 r GM 2 r GM 3 +
G M a tG D2+ G D ly G T2,
It has been given official names such as GT3 and GT1b, and is widely distributed in the living tissues of various higher animals. In recent years, gangliosides have suddenly attracted attention as it has been revealed that they act as receptor molecules for hormones and bacterial toxins, and express proliferation and differentiation-promoting factor activities. However, most gangliosides are naturally derived and their structures are limited, making it difficult to systematically study the relationship between their chemical structures and physiological functions. Even the scope of searching for useful substances is limited. For this reason, synthetic studies on analogs, derivatives, glycosides, and sialo-oligosaccharides are being actively conducted, and various derivatives are being synthesized, but research is still in its infancy, and new derivatives are expected to emerge. Further new developments are awaited.

[Object of the Invention] The present invention was made in view of the above-mentioned circumstances, and an object of the present invention is to provide various novel gangliosides, analogs thereof, and useful intermediates thereof.

[Configuration of the Invention In order to achieve the above object, the present invention has the following configuration.

"(Engineering) The following general formula [I]. [II, [■], [rV
] or a compound represented by [■] [wherein R represents an aliphatic acyl group, and R1 represents a hydrogen atom or a lower alkyl group]. R2, R3R4 and R5 both represent a hydrogen atom, or each independently represents an acyl group. R6 is -N, -NO2 or -NH
CORa (wherein, Ra represents a saturated or unsaturated alkyl group having 1 to 30 carbon atoms, and may be linear or branched), and n represents an integer of 0 to 20. However, when Rl is a hydrogen atom, R2 to R5 all represent a hydrogen atom, and when Rl is a lower alkyl group, R2 to R5
Both represent acyl groups (which may be the same or different). [In the formula, R, R', R2, R3, R', R5, R' and n are the same as above. However, when R+ is a hydrogen atom, R2~
Each of R5 represents a hydrogen atom, and when Rl is a lower alkyl group, all of R2 to R5 represent an acyl group (which may be the same or different). ] [In the formula, H1 is -NtlCOCH3, -NHCOCH
(Ra)Rb or -NHCOCIl2CH(Ra)Rb
(However, Rh represents a hydroxyl group or an acyloxy group, and R
a is the same as above. ), R, R', R2, R3,
R', R5 and n are the same as above.

However, when R1 is a hydrogen atom, R2 to R5 all represent a hydrogen atom, and when R1 is a lower alkyl group, R2 to
All R5's represent an acyl group (which may be the same or different). Also, R7 is -NHCOC
tl(Ra)Rh or -NHCOCll2CH(Ra)
Rb, and when Rb is a hydroxyl group, R1 to R5 are all hydrogen atoms. ] [In the formula, R8 represents a saturated or unsaturated alkyl group having 1 to 30 carbon atoms (which may be linear or branched) or a penzyloxy group. R, R', R2R3,R
' and R5 are the same as above. However, when R1 is a hydrogen atom, R2 to R5 all represent a hydrogen atom, and when R1 is a lower alkyl group, R2 to R5 are all acyl groups (which may be the same or different). represents.
Furthermore, when R8 is a penzyloxy group, R1 to R5
All represent acyl groups (which may be the same or different). ] [In the formula, R, R', R2, R3 R' and R8 are the same as above. However, R! When is a hydrogen atom, R2 to R4 all represent a hydrogen atom, and when Rl is a lower alkyl group, R2 to R4 all represent an acyl group (which may be the same or different). Also, when -R8 is a penzyloxy group, all Rl-R4 are acyljf
5 (which may be the same or different). ] (2) A compound represented by the following general formula [VI] or [■]. (In the formula, TAS represents a trialkylsilyl group, R
l', R2', R'' and R'' represent an acyl group, and R is the same as above. ) (In the formula, R, R", R2' are the same as above.) R", R" and TAS are (3) a compound represented by the following general formula [■] or [IX] (in the formula, R9 is lower alkyl represents a group, R, R" and R"
is the same as above. ) (In the formula, R, Rl'R2' and R9 are the same as above.

)” General formula [■ko, [II], [II
I], [■ko, CVko[:Vf]. [■],
As for R in [■] and [IX]. For example, aliphatic acyl groups such as an acetyl group, a probionyl group, a butanoyl group, etc. may be mentioned, and as R1 in general formulas [1] to [V], in addition to a hydrogen atom, for example, a methyl group, an ethyl group,
Examples include lower alkyl groups such as probyl group and butyl group,
Examples of R" in general formulas [■] to [IX] include lower alkyl groups such as methyl group, ethyl group, propyl group, butyl group. R2 in general formulas H] to [V]
, R3 and R4, and R5 in the general formulas [11 to [rV]] include, in addition to a hydrogen atom, for example, an acetyl group,
Examples include acyl groups such as a probionyl group, a butanoyl group, a benzoyl group, and R in general formulas [VI] to [■
2 1. The scale 3' and R4' in the general formulas [VI] and [■] are, for example, an acetyl group, a probionyl group,
Examples include acyl groups such as butanoyl group and benzoyl group.

General formula [rco and EUE ii6R6c. -N3,
-N}I2 or -NHCORa, and as Ra, for example, -CI+,, -C2HSt -C3H7# -
c4H9, -C5FII++ -C71{15+ -
C9'+9+ -CIlH23+ -CI3H27+ -
CI5'31+ -CI7H3S+ -C23H47+
-C3oH61y -Cl7H311 -CI7H32
Examples include saturated or unsaturated linear or branched alkyl groups having 1 to 30 carbon atoms, such as 1-C+7lb3. R7 in the general formula [m] is -NHCOCH3, -NHC
OCH(Ra)Rb or -NHCOCH2CH(Ra)
Rb represents a hydroxyl group, and acyloxy groups such as an acetoxy group, a propionyloxy group, a butanoyloxy group, and a benzoyloxy group. Examples of Ra include the aforementioned saturated or unsaturated alkyl groups having 1 to 30 carbon atoms. R8 in the general formula [[V] and CVE represents Ra or a penzyloxy group. Examples of Ra include the alkyl groups described above.

TAS in the general formulas [VI] and [■ represents a trialkylsilyl group, and examples of the trialkylsilyl group include trimethylsisol group, triethylsilyl group, triisopropylsilyl group, dimethyl t-butylsilyl group. Examples include groups.

Examples of R9 in the general formulas [■] and [IX] include lower alkyl groups such as a methyl group, an ethyl group, a probyl group, and a butyl group.

Gangliosides and intermediates thereof according to the present invention are produced, for example, as follows.

First, general formulas [■] and [IX] are initial intermediates for producing gangliosides represented by general formulas [1] and [U].
The alkylthiosialic acid derivative represented by is synthesized, for example, according to the method described in JP-A-63-41494.

That is, first, an acylthiosialic acid derivative represented by the general formula [■a or [IXa] (where R, R'' and R2' are the same as above) is mixed with an alkyl metal alkoxide in an alcoholic solvent. When the reaction is carried out at low temperature and the solvent is distilled off, the compound [■b] or [IXb] (wherein M represents a metal atom, and R, R" and R" are the same as above) is obtained. This is dimethylformamide (DMF)
), the desired alkylthiosialic acid derivative can be obtained by reacting it with an alkyl halide at room temperature or slightly warmed, followed by post-treatment using a conventional evaporator. It is optional to purify this by column chromatography or the like, if necessary.

Next, this alkylthiosialic acid derivative is converted into a 2-α-0-glycoside compound of sialic acid represented by the general formula [VI] or [■], for example, as described below. That is, first, the above-mentioned alkylthiosialic acid derivative is dissolved in methyl triprate (preferably sufficiently dried) in a polar solvent without a hydroxyl group such as acetonitrile, propionitrile, petite nitrile, or nitromethane.
In the presence of a Lewis acid such as trifluoromethanesulfonate (trifluoromethanesulfonate), trimethylsilyl triflate (trimethylsilyltrifluoromethanesulfonate), dimethyl(methylthio)sulfonium triflate (DMTST), etc., at a low temperature, e.g., below room temperature, preferably -5°. The following general formula [VIa] which is a sugar acceptor with C or less (in the formula, R'' and T
AS is the same as above. ) for several hours to several tens of hours. After the reaction, post-treatment may be carried out according to conventional methods, such as filtering off insoluble materials and concentrating the filtrate.
Purification by column chromatography or the like is optional, if necessary.

The thus obtained 2-α-0-glycoside compound of sialic acid (some of the hydroxyl groups are unmodified) is reacted with acetic anhydride in pyridine anhydride at room temperature for several hours to several tens of hours. When acylated according to the method, 2-α- of the sialic acid represented by the general formula [VI] or [■] according to the present invention can be obtained.
O-glycoside compounds are easily obtained.

The gangliosides represented by the general formulas [1] and [U] according to the present invention are synthesized in the following manner using the 2-α-0-glycoside compounds thus obtained.

That is, first, if a 2-α-0-glycoside compound of sialic acid represented by the general formula [VI] or [■] is required, it is prepared in a suitable non-polar solvent, for example, BF, monoether, NaBF4.
By treating with a fluorine compound capable of generating fluorine ions (F-) such as , KBF4, LiBF4, or a Lewis acid such as FeC13, the protective group for the hydroxyl group at the 1-position of the reducing end, that is, the trialkylsilyl group, can be am Let. The reaction is usually carried out at a low temperature (about 0° C. to room temperature), and the reaction time is about 1 to IO hours. After completion of the reaction, post-treatments such as solvent extraction and solvent distillation may be carried out according to conventional methods, and purification by column chromatography or the like may be optionally performed as necessary. Next, this compound is reacted with trichloroacetonitrile in a nonpolar solvent such as dichloromethane, dichloroethane, or chloroform in the presence of a basic catalyst to convert the hydroxyl group at the 1-position of the reducing end into trichloroacetimidization. (Nll) Set as CCL3. As the basic catalyst, for example, 1,5-diazabisic acid [5.3. Organic bases such as Ooundecar-5-ene (DB[I) and 1,5-diazabisic-[4.3.0]noner-5-ene (DIIN), e.g. NaH, K2CO3, Na2CO3
Examples include inorganic bases such as. The reaction is usually carried out at a low temperature, for example around 0°C or lower, and a reaction time of several hours is usually sufficient. After the reaction is complete, post-treatments such as solvent distillation may be carried out according to conventional methods, and if necessary, purification may be carried out by column chromatography, etc. -QC (NH
) CCI: A 2-α-0-glycoside compound of sialic acid having a + group is mixed with a Lewis acid such as BF3-ether or methyl triplate (methyl trifluoromethanesulfonate) in a nonpolar solvent such as dichloromethane or dichloroethane. In the presence of the following general formula [1a] N3 (wherein, R51 represents an acyl group, and n is the same as above.
) When reacted with the azidosphingosine derivative represented by In formula [11 or [II], R6=-
A novel compound of N3 according to the present invention can be obtained in high yield. The reaction is usually carried out in the presence of a dehydrating agent such as molecular sieves, the reaction temperature is usually around 0°C, and the reaction time is usually about 1 to 10 hours.

After completion of the reaction, post-treatments such as removal of insoluble matter, solvent extraction, and solvent distillation may be carried out according to conventional methods, and purification by column chromatography or the like is optional if necessary.
If this compound is reduced under weak reducing conditions, the general formula [1]
Or in [II], the novel compound of the present invention with R6=-NH2 is obtained in high yield, and by further N-acylating it with a fatty acid, the compound of the general formula [I] or [■ R 6
The compound of the present invention of = -NHCORa (Ra is the same as above) is obtained in high yield. The reducing agent used to reduce the azide is preferably an acidic reducing agent such as hydrogen sulfide, but is not particularly limited to this. Any reducing agent that does not reduce heavy bonds or remove acyl protecting groups may be used. Reaction conditions naturally vary depending on the reducing agent and reduction method used, and are selected as appropriate. For example, when hydrogen sulfide is used as the reducing agent, the reaction conditions are usually pyridine-water mixed solvent (for example, 2 to 1 liter of pyridine to one liter of water).
10v01. (a mixed solvent) at around room temperature for 10 to 60 hours. After the reaction is completed, post-treatment can be carried out according to a conventional method, but usually the amino compound is not isolated after the reaction solution is concentrated to dryness, but it is directly carried out in the next step, that is, N
-Subjected to acylation process. The fatty acids used in the N-acylation process include saturated or unsaturated fatty acids having 2 to 31 carbon atoms, and may be linear or branched, such as acetic acid, propionic acid, butyric acid, etc. , cabric acid, lauric acid, myristic*, valmitic acid, octadecanoic acid (stearic acid), tetracosanoic acid (lignoceric acid), melisic acid, oleic acid, linoleic acid, etc., but are not limited to these. Needless to say. N-acylation reaction usually involves 1,3-
In the presence of a dehydration condensing agent such as dicyclohexylcarbodiimide (DCC) or l-ethyl-3-(3'-dimethylaminoprobyl)carbodiimide (WSC), in a suitable reaction solvent such as dichloromethane, dichloroethane, chloroform, etc. , by reacting for several hours to several days at room temperature or with slight heating. After completion of the reaction, post-treatments such as solvent extraction and solvent distillation may be carried out according to conventional methods, and purification may be carried out by column chromatography or the like as necessary.

In the general formula [■ or [■] obtained in this way, R'
=-Nf{If the protective groups for the hydroxyl group and the carboxyl group of the compound of CORa are sequentially dissociated according to a conventional method, in the general formula [I or [■], R', R2, R3, R
', gangliosides in which RS is a hydrogen atom can be obtained in high yield. Removal of the hydroxyl protecting group (acyl group) is performed using the above N
- Compounds obtained by acylation, e.g. methanol,
Dissolve in an alcoholic solvent such as ethanol (preferably sufficiently dehydrated), add an appropriate amount of an alkali, such as a metal alcoholate such as sodium methylate or sodium ethylate, and heat at 0 to 50°C for several hours. The reaction may be carried out with stirring for several tens of hours, and the protective group for the carboxyl group can be removed by removing the acyl protecting group, then adding a small amount of water to the reaction solution and reacting with M1# for several hours to several tens of hours. All you have to do is react. After the hydrolysis reaction is completed, post-treatment may be carried out according to a conventional method, such as neutralizing the reaction solution using, for example, a cation exchange resin, filtration, and concentrating the filtrate to dryness.

The gangliosides represented by the general formula [m] according to the present invention can be easily obtained according to the above synthesis method.

That is, alkylthiosial l! represented by the general formula [■] or [IX]! ! Instead of the derivative, an alkylthiosialic acid derivative represented by the general formula [X] (wherein R, R", r"Ii and R9 are the same as above).

) as an initial intermediate, a compound represented by the general formula [mal (wherein R, Rl', R2', R'', R4#, R'' and n are the same as above) can be obtained. This is added to the general formula [XI
or [XII] HOOCCH(Ra)Rb' [XI] (in the formula,
Rh' represents an acyloxy group, and Ra is the same as above.
) H○○C C H 2 C H (R a ) Rh
' C
h or -NHCOC! {2Cll(Ra)Rh is obtained, and when acetic anhydride is applied, R 7
=-NHCOCH3 is obtained. If the protective groups for the hydroxyl group and the carboxyl group of the thus obtained compound are sequentially removed as described above, the general formula [11I
], R', R2, R3, R4 and R5 are hydrogen atoms, and R7 is -NHCOCH3, -NHCO
Ct{(Ra)OH or -N11COCI'l2CI{
A ganglioside which is (Ra)Of{ is obtained.

Further, the gangliosides represented by the general formulas [rV] and [V] according to the present invention can be synthesized as follows according to the synthesis method of the gangliosides represented by the general formula [11 or [■]. ．． That is, a compound represented by the general formula rUIb (wherein R, Rl', R2', R" and R" are the same as above) which is used in the synthesis of the intermediate represented by the general formula [mal] and general formula [XIII] or [XIV
] (In the formula, Bn represents a benzyl group, and R5' is the same as above.) H○ ,,, 72/'\\, 22/N H C O O
An N-(penzyloxycarbonyl)amino alcohol derivative represented by BnEXIVco (in the formula, Bn is the same as above) is dissolved in a nonpolar solvent such as dichloromethane or dichloroethane, such as BF3-ether or methyl trifluoride. When reacted in the presence of a Lewis acid such as chloride, -QC(NH)CC13 groups of the general formula [mbl (in the formula, Bn and R'' are the same as above) -o-,, /\
, /NHC○○Bn (in the formula, Bn is the same as above), i.e., a compound of the general formula [IV] or [V]
The compound of the present invention in which R8 is a penzyloxy group can be obtained in high yield. Next, if this benzyl group is eliminated,
With the generation of carbon dioxide gas, an amino form is produced, and by further N-acylating it with a fatty acid, the book of R8=Ra (Ra is the same as above) in the general formula [rV] or [V] is produced. Inventive compounds are obtained in high yields. The above-mentioned elimination of the benzyl group is mainly carried out by catalytic reduction, and the catalyst used at that time is, for example, palladium-activated carbon (Pd-C
) are preferred, but are not particularly limited to these, but any one that has the ability to release the benzyl group to form an amino form and does not release the acyl-carrying M group can be used. It is also possible.

Reaction conditions naturally vary depending on the desorption method and reduction catalyst used, and are selected appropriately. For example, when catalytic reduction is carried out using 10% Pd-C as a catalyst, the reaction conditions are usually 1 to 10% at around room temperature in an alcoholic solvent. This is done by reacting for 5 hours. After completion of the reaction, post-treatment may be carried out according to conventional methods, but usually the amino compound is not isolated after the reaction solution is concentrated to dryness, but is directly subjected to the next step, that is, the N-acylation step. The type of fatty acid used in the N-acylation step and the N-acylation method are the same as those for the synthesis of gangliosides of general formula [I] or CUE. After completion of the reaction, post-treatments such as solvent extraction and solvent distillation may be carried out according to conventional methods, and if necessary, purification may be carried out by column chromatography or the like.

The protective groups for the hydroxyl and carboxyl groups of the thus obtained compound were changed to 115! in the same manner as in the synthesis of gangliosides represented by the general formula CIE or [U]. If separated, a ganglioside in the general formula [IV] in which R', R2, R3R4 and R5 are hydrogen atoms and a ganglioside in the general formula [V].
Gangliosides having R', R2, R3 and R4 hydrogen atoms are easily obtained.

In the present invention, the compound represented by the general formula [VIal, which is used as a sugar acceptor for glycosidation, can be easily synthesized, for example, as follows. That is, first, a compound represented by the general formula [VIb] (wherein AS is the same as above) is subjected to a conventional method for benzylation of a hydroxyl group.
For example, in non-polar solvents such as benzene, toluene, chloroform, dichloromethane, dichloroethane, etc.! M-ized G-n
-Butyltin, tetra-n-butylammonium bromide and benzyl bromide are heated to react with the general formula [V
A compound represented by Ic (where Bn and TAS are the same as above) is then added to an acylating agent (for example, benzoyl chloride) in the presence of a base such as pyridine or triethylamine according to a conventional acylation method. , acetic anhydride, etc.) under cooling if necessary to selectively acylate the 2-, 6-, and 6'-positions (in the formula, R'', Bn and TAS are the same as above).

). Thereafter, if this is reduced according to a conventional method using, for example, Pd-C as a catalyst and formic acid as a hydrogen donor, only the benzyl group at the 3' position is removed and the general formula [
(2) A compound represented by a] is obtained.

The compound represented by the general formula [VIb], which is a starting material for synthesizing the compound represented by the general formula [VIa], was first synthesized by the present inventors using the corresponding M group or azino sugar as a raw material. Headline, patent application filed (Patent Application No. 1707, 1983)
It can be easily obtained by the following method. That is, first, the corresponding saccharide or amino sugar was acylated using an acylating agent (e.g. acid anhydride, acetyl chloride, etc.) by a conventional method, and then a halogen group was introduced into the 1-position using hydrogen bromide or the like according to a conventional method. After that, Hg(CN)2 and Hg
Brz t^g2co 3 and AgC104, A. 2C
When o3 is reacted with TASC2H40H (however, TAS is the same as above) in the presence of a condensing agent such as I2y^gc104 or HK(CN)2, the hydroxyl group at position 1 becomes a 2-(trialkylsilyl)ethyl group. A sugar derivative or an amino sugar derivative is obtained in which the other hydroxyl group is protected by an acyl group.If this is deacylated by a conventional method such as treatment with sodium methylate in methanol, the general formula The compound represented by [VIb] can be easily obtained.

Further, DMTST used in the glycosidation reaction is described in the known document J. Chem. Soc. , Perkin T.
rans. , ff , 1569-1.572 (198
According to the method described in 2), it is prepared from dimel disulfide and methyl trifluoromethanesulfonate and used.

The azidosphingosine derivative represented by the general formula [■a] used in the production method of the present invention is, for example, JP-A-62
According to the method described in 207247-207247, the general formula [
Ib] N3 (wherein n is the same as above) is combined with azidosphingosine, and the primary hydroxyl group at the 1-position is protected with an appropriate protecting group, such as dimethyl-butylsilyl group, and then, for example, Using an acylating agent such as benzoyl chloride or acetic anhydride, the hydroxyl group at the 3-position is acylated by a conventional method, and then, for example, the hydroxyl group at the ↓-position is removed with an ether atmosphere. Since it can be easily obtained by this method, it is sufficient to use the product obtained in this way.

Examples and reference examples are shown below, but the present invention is not limited to these examples and reference examples in any way. In addition, the abbreviations used in the NMR column in Examples and Reference Examples are as follows.

Me: methyl group, Ac: acetyl group, ph: phenyl group. [Example] Reference example 1. 2-(+-limethylsilyl)ethyl 0
-(6-0-penzoyl-β-D-galactopyranosyl)-(l→4) -2.8-di-O-penzoyl-β-
D-glucobyranoside (in the general formula [VIal, R
4'=benzo'yl group, TAS= }limethylsilyl Go compound.

Hereinafter, it will be abbreviated as compound (3). ).

(1) 2-(}limethylsilyl)ethyl 0-(3-O
-benzy-β-D-galactopyranosyl) ~(1→4
)-β-D-glucopyranoside (hereinafter abbreviated as compound (1)) 6.59 g of 2-(trimethylsilyl)ethyl β-D-lactoside was dissolved in methanol room, and (
n-C4Hc+)2SnO 4.92K was added, and the mixture was stirred and reacted under heating and reflux for 3 hours. After the reaction, the reaction solution was concentrated under reduced pressure, thoroughly dried, and 200 ml of benzene was added to dissolve it, resulting in (n-C4Hc+) 4NBr 4.8
0 g and 14.2 ml of benzyl bromide were added, and the mixture was stirred and reacted under heating under reflux for 3 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, n-hexane was added to the residue, excess benzyl bromide was removed by a decanting method, and the resulting syrup was subjected to column chromatography [filling material: Wako Gel C-200 (Wako Pure Chemical Kogyo Co., Ltd. (trade name), eluent: ethyl acetate/n-hexane = 4/1 to give 5.96 g of compound (1) (yield 7).
5.2%).

m. p　　164-167℃.

[α] o=0.14' (C=L48, CI
42Cl2) -I R y2'j2(am-')
: 3700-3100 (011). 3000
~2850 (C}I), 860, 840 (trimethylsilyl), 74Q, 700 (phenyl). NMR (CD30D) δppm: 7.41
-7.21 (m, 511, -CH2-CafJx)
,4.72,4.58 (2d,2N,J,,,=
11.9}1z, Cllz-C6Hs).
4.34 (d, LH, J+2・=8.1H2,
l{-1'). 4.26 (d, LH,
J+. 2=7.7t{z,}l-1). 3.9
7(near d, IH, J3=3-3Hz+H
-4'), 3.35 (ddv IH, J23=9
．． 5Hz r H-3'), 3. zt
(near t, Ill, J2. ]=8}+2,
H-2) - 0.96 (m, 211,
-OCH2CL2Si), -0.02 (st 9
t-1tSiMe]).

(2) 2-(trimethylsilyl)ethyl O-(610-penzoyl-3101 benzyl-β-D-galactopyranosyl)-(1→4) -2.6-di0-penzoyl-β-D Synthesis of glucopyranoside (hereinafter abbreviated as compound (2)).

After dissolving 1.32 g of compound (1) in a mixed solvent of 8 ml of pyridine and 20 ml of dichloromethane and cooling it to -50'C, a solution of 1.2 ml of penzoyl chloride dissolved in 15 ml of dichloromethane was added dropwise thereto for -30 minutes. The mixture was stirred and reacted. After the reaction was completed, methanol was added to decompose excess benzoyl chloride, and then the reaction solution was concentrated under reduced pressure. Dichloromethane was added to the residue for extraction, and the dichloromethane layer was washed with hydrochloric acid and water, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The resulting syrup was subjected to column chromatography [filling material: Wakogel C-200, eluent:
The mixture was subjected to CH2C12/Cl30H=200/11 to obtain 1.40 g (yield 67%) of compound (2).

[αko. =+14.01 (C=0.856,CH
C13).

I R v, A. 'Kei- (cm-1): 3700
-3100 (OH). 3100~2800 (C
H). 1730. 1260 (ester) −
860,840 (trimethylsilyl), 710
(Phenyl). NMR (CDC13-CD30D)
δppm: 8.18-7.38 (n, 20H
, OBZX3, -CH2-C6111). 5.
33 (dd, LH, J,, 2=8.06Hz,
J2. 3=8.15Hz, H-2) + 5.04
(dd, IH, J., I, = 11.91tlz,
t{-6) − 4.85 (s, 2H, −Cll
z-C6H5), 4.73 (d, IH, J, .
2=8.06Hz, H-1). 4.63 (d
d, IHt Jgem=11.90Hz, J5.6
=5-86Hz, }I-6)+4.51 (d,
IH, J. ,2. =7.88Hz, H-1')
．． 3.53 (dd, IH, J2・3・=9.5
3.J3.. 4.=3.3011z, H-3'), 0
．． 96 (m, 2}1, -OCH2Cjl, -Si
)． 0 (s, 911, Me3Si). (3)
Preparation of Compound (3) 1.40 g of Compound (2) was dissolved in 50 ml of methanol, and 10% Pd-C I. Og and 1 ml of formic acid were added, and the mixture was stirred and reacted at 60°C for 2 hours. After the reaction was completed, the reaction solution was filtered to remove insoluble matter, and the 'a solution was concentrated under reduced pressure, and the resulting syrup was subjected to column chromatography [filling material: Wakogel C-200, eluent: CH2C12/CH30]
1+=50/1] and 880 mg of compound (3)
(yield 70%).

[a] o=+11.03° (C=0.5
8, CHC13).

I R v,4i4"(am-')=3700~3
100 (OH), 3000~2800 (CH)
．． 1720. 1260 (ester), 8
60,840 (}limethylsilyl), 700 (
phenyl).

NMR (CrlC13-CD30D) δppm
:8.17 7.40 (m, 15H, OBzX
3), 5.33 (dd, LH, Jl, 2=8.
06t{z, J2, 3=9.61Hz, H-2)
．． 4.99 (dd, LH, J(e,=10.
28Hzg H-a). 4.81 (dd, Ill
, J,,. =11.91Hz, Js6=3.30H
z, H-6). 4.74(d, 1}1, Jl
−． 2- = 8.06tlz, H-1). 4.64
(dd, LH, J(e+,1=11.9011Z,
J5,6='-5.86Hz, H-6), 4.5
0(d,LH,J1・,26 =7.88Hz,H−1
').

Example 1. 0-(5-acetamido-3,5-dideoxy-β-L-arabino 2-heptulopyranosilone a)-(2→3)-0-(β101 galactopyranosyl)-(1→4 )-0-(β-D-glucopyranosyl)-
(1→1)-(23,3R,4E)-2octadecanamido-4-octadecene-1,3-diol (general formula [
In I, R=acetyl group, R1=R2=R3=R'=
R5=hydrogen atom, R6=-NHCOC, 7H351
Compounds with n=12. Hereinafter, the compound (l2> is abbreviated.) (
1) Methyl (methyl 5-acetamido-4,7-di-0-acetyl-3,5-dideoxy-2-thio β-thi-arabino-2-hepturoviranoside)onate (general formula [■ where R= R''=acetyl group, Rl'=R9=
Compounds with methyl group. Hereinafter, it will be abbreviated as compound (4). ) methyl 5-aceto-4,7-di-0-acetyl-2-S-acetyl-3,5-dideoxy-2-thio β-L-arabino 2-hepturoviranosonate 4.2
1 g (10.4 mmol) in 100 ml of anhydrous methanol
Dissolved in NaOC83 218m under cooling to -40℃
A solution of g (9.5 mmol) dissolved in 5 ml of methanol was added, and the reaction was stirred for 5 minutes. After the reaction, the mixture was concentrated at 0°C to obtain an amorphous compound. Add this to anhydrous DMF
The solution was dissolved in 44 ml, 1-0 ml of methyl iodide was added, and the mixture was stirred and reacted at room temperature for 3 hours.

To this was added 8 ml of pyridine and 5.5 ml of Kumazu acetic acid, and the reaction was stirred at room temperature for 24 hours. The solvent was distilled off, and the residue was extracted with methylene chloride, washed with 2M hydrochloric acid and then with water.
After drying Na2SO4, the silamp obtained by concentration was purified by column chromatography [Wakogel C-209, eluent: ethyl acetate/n-hexane (5/l)] to obtain 3.43 g of compound (4). obtained as. Yield: 87.
3%. [α]. : -12.4゜ (C=1.05, CHCh
).

NMR (CDCl3) δppm: 1.
92 (s, 3tl, AcN), 2.06, 2.10, 2
．． 17 (3s, 9H, 2AcO, MeS), 2.74 (
dd, II-1, J3. ,3@=12.6Hz,J3*
．． 4=4.6Hz, H-3e), 3.64(m, LH
, J5. 6”10.6Hz, J6.7=3.1Hz
, H-6), 3.82 (s, 3H, MeO), 4.05
(qeIHvJ4.s:10.6
Hz), 4.25 (m, 2H, H-7.7'), 4
．． 88 (ddd, IH, H-4), 5.72 (d, IH
,NH).

(2) 2-(}limethylsilyl>ethyl 0-(methyl 5-acetamido 4,7-di-0-acetyl-3,
5-dideoxy-β-L-arabino-2-heptulopyranocylonate)-(2→3)-0-(6-0-penzoyl-β-D-galactopyranosyl)-(l→4)-2.
Synthesis of 6-di-0-penzoyl-βD-glucobyranoside (hereinafter abbreviated as compound (5)) 2.08 g (5.5 mIIlol) of compound (4) and Reference Example 1. Compound (3) obtained in 2.11: (2.8 mm
ol) in 30 ml of anhydrous acetonitrile, and then dissolved in molecular sieves 3A4. 27g was added and stirred overnight. To this, 7.35 g of molecular sieves 3A containing 5.66 g of DATST was added at -20°C, and -1
The mixture was stirred and reacted at 5°C for 24 hours. After the reaction was completed, the reaction solution was filtered, and dichloromethane was added to the filtrate for extraction. The dichloromethane layer was washed with an aqueous sodium carbonate solution and water, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the resulting silamp was subjected to column chromatography [filling material: Wakogel C-
200, eluent: ethyl acetate/n-hexane = 2/11
1.45 g of compound (5) was obtained. Yield 48%
．． Recrystallization from ethyl acetate-hexane gave needle-shaped crystals. m-p. 194-196℃ [α]o= 10.6゜ (C: 0.83, CHC
l]) -I R y 22j,"(cm-
'): 3700~3200 (OH, N
il), 1730. 1270 (ester),
1670.1530 (amide),? 50,840 (
trimethylsilyl). 710 (phenyl).

NMR (CDCI3) δppn+
: Lactose unit; 0.86 (m, 2H, Me3Si
"hCH20), 3.56 (m, IH, 3sicH
2 Deaf, :0) − 4.40(d, IH-Jl, 2=
7.7Hz, H-1), 4.57(dd, IH, J5,
6=5.4Hz, J6. 6.=12.0Hz, H-
6), 4.63 (d, LH, J1・z・=8.4Hz
, H-1') - 4.74 (dd, IH, H-6)
．． 5.24(dd,i}l,.12.3=9.0H
z). 7.27-8.08 (m, 15H, 3Ph).
Sialic acid unit; 2 − 6 5 ( d d + I
H s J 3 a, 3 e ” 13-2
11 z y J 3 e . 4 ”4-9'Z*
H-3e), 3.80 (s, 3H, MeO), 5.03
(m, IH, H-4), 5.70 (d, IH, Js.
h■=9.3Hz, NH). (3) 2-(}limethylsisol)ethyl 0-(methyl 5-acetamido 4,
7-di-0-acetyl-3,5-dideoxy-β-L-
arabino~2-heptulopyranocylonate)-(2→3
)-0-(2.4-di-0-acetyl-6101penzoyl-β-D-galactobyranosyl)=(1→4)-3
-0-acetyl-2,6-di-0-benzoyl-β-D
- Glucopyranoside (general formula [■, where R=R2'
= R3'acetylg, R" = methyl group, R1 = benzoyl group, TAS = trimethylsilyl group compound. Hereinafter abbreviated as compound (6)) Synthesis of compound (5) 500 mg (0.46 mmol) in 10 ml of anhydrous pyridine 5+nl of acetic anhydride was added and allowed to react overnight at 30°C. After the reaction was completed, column chromatography [filling material: Wakogel C-200,
Eluent: ethyl acetate/n-hexane = 5/4]
557 mg of compound (6) was obtained. Yield 98%. [ α
Co = − 29.2” (C = 0.89, (J
IC13). NMR (CDCI, -CD300:
1/1) δppm: lactose unit; 0.
85 (m, 2H, He 3SL Denhi CH 2
0), 3.53 (m, IH, Me3SiCH2Qhi0)
- 4.58 (d, LH, J,, 2=8.1Hz,}
I-1) - 4.65(d, [1, J12・=7.8
Hz, H-1'), 5.00 (dd, IH, J2.
, 310.1Hz, H-2'), 5.18(nea
r d, LH, H-4'), 5.20 (dd, LH, J
2. 3=9.5}1z,H-2), 5.46(t
, 18, J2. 3=J3, 4=9.5Hz, H-3
), 7.28 to 8.04 (m, 15H, 3Ph). Sialic acid unit; 1-68 (t, LH+J3m. 3e"
J3m. 4=12.5Hz, H-3a), 1.88(
s, 311, AcN), 2.63 (dd, LH, J3e
4"4.8tlz, H-3e), 3.68(s, 3H,
MeO)-4.96 (lIl, IH, H-4). Acetyl group; 1.99, 2.01, 2.03, 2.11, 2
．． 18(5s,15}1,5AcO). (4) 0-(methyl 5-acetamido-4.7-di0-acetyl-3.5-dideoxy-β-L-arabino 2-heptulopyranocylonate)-(2→3)-0-(2.4 -di-0-acetyl-6-0-penzoyl-β-D-galactopyranosyl)-(1→4)-3-,0-acetyl-2,
6-di-0-penzoyl-β-D-glucopyranose (
Hereinafter, it will be drunk with compound (7).

) Synthetic compound (6) 520 mg (0.43 mmol) was dissolved in 10 tablets of dichloromethane, cooled to 0°C, and B
Drop 320 mH of P3-ethyl ether and heat to 0-5°C.
The mixture was stirred and reacted for 10 hours. After the reaction was completed, 30 ml of dichloromethane was added for extraction, and the dichloromethane layer was washed with aqueous sodium bicarbonate and water, dried over anhydrous Na2SO4, and concentrated. The obtained residue was subjected to column chromatography (filling material:
Wakoge/L/C-200, eluent: CH3CL, C
H3CI/CH30H=50/1) to give compound (7
) 470 ■ was obtained. Yield 98.5%.

[α] o” +26.9@(C=0.62, CHC
13). IRV 4S'-'(am-')
3700-3150 (OH, NH), 1750,
1230 (ester). 1B70, 1540
(amide), 720 (phenyl). (5) 0-(methyl 5-acetamido-4,7-di0-acetyl-3,5-dideoxy-β-L-arabino 2-heptulopyranocylonate)-(2→3)-0-
(2.4-di-0-acetyl-6-0-penzoyl-β
-D-galactobyranosyl)-(l→4)-3-0-acetyl-2,6-di-0-penzoyl-α-D-glucopyranosyl trichloroacetimidate (hereinafter abbreviated as compound (8)). Bo compound (7) 440+ng
(0.4 mmol) was dissolved in 3ffi1 of dichloromethane and cooled to -5°C. Thereto were added 0.8 ml of trichloroacetonitrile and 31 mg of DB1, and the mixture was reacted with stirring at 0°C for 3 hours. After the reaction was completed, the reaction solution was concentrated, and the resulting syrup was subjected to column chromatography (y?.Filler: Wakogel C-200, eluent CH2C12/CH3
0H=10/1) to obtain 400 ml of compound (8). Take-up rate 80.6%0 [α co= +37.8” (C=0.69, CH
Cl3) NMR (CDC13) δppm: Lactose unit; 4.64 (d, IN, J1.2:7.
9}1z,}I-1'). 5.04(near t,
1}1, H-2'), 5.20Cnear d, J-3
．． 1Hz, H-4'). 5.26 (dd, IH, Jl
, 2=3.911z, J2. 3=IO. 211z,
H-2), 5.84 (near LILJ3 4”9.
511Z, I+-3), 6.68(d, Ill, Jl
．． 2"3.9}IZ, I+-1), 7.39 ~ 8.0
4 (m, 15H, 3Ph), 8.56 (s, LH, C=
NH). Sialic acid unit; 1.70 (t, LH, J3m
．． 3e"J3a. 4"l2-9t{z, H-3a)
, 1.89 (s, 3H, AcN), 2.53 (dd, 1
8, J3.4=4.7Hz, H-3e), 3.75(s
, 3H, MeO). 3.93 (qelH+J4.s
=J, NH=J,, 6=10.1Hz, H-5), 4
．． 96 (IIl, LH, H-4), 5.42 (d, IH
, Nu). Acetyl group; 2.00, 2.03, 2.0
4, 2.13, 2.17 (5s, 15H, 5AcO). (6') O-(methyl 5-acetamido-4,
7-G〇1acetyl-3,5-dideoxy-β-L-
arabino 2-heptulopyranocylonate)-(2→3
)-0-(2.4-di-O-acetyl-6-0-penzoyl-β-D-galactopyranosyl)-(1→4)-0
-(3-0-acetyl-2,6-di-0-penzoyl-β-D-glucovira/S/lz)-(1-+1)-(
25,3R,4E)-2-azido-310-penzoyl-4-octadecene-1,3-diol (general formula [■]
In, R=R2=R3=acetyl group t R'=methyl group, R4=R5=benzoyl group y R' ” N 3
360 mg (0.29 mmol) of compound (8) and (2
S,3R,4E)-2-azido-310-penzoyl-4-octadecene-1,3-diol (hereinafter referred to as compound (
10). ) 24dllllg<0.58mmo1
) was dissolved in dichloromethane 8111, 5.0 g of Molecular Sieves 4A was added, and the mixture was stirred at room temperature for 30 minutes.
After cooling this to 0°C, BF3-diethyl ether 8
2IIlκ was added, and the mixture was stirred and reacted at 0°C for 4 hours.

After the reaction was completed, the reaction solution was filtered, and the filtrate was extracted with dichloromethane. The dichloromethane carcasses were washed sequentially with aqueous sodium bicarbonate and water, dried with anhydrous Na2SO4, and concentrated. The resulting residue was subjected to column chromatography (filling material: Wakogel C-20).
0, eluent: ethyl acetate/n-hexane = 3/1) to obtain 340IIg of compound (9). Yield 7
8.0%. [α] o= 11.3@(C=0.76, CHC
l3). rRV! ! ! - (cm-')
3350 (N}l). 2940t2850 (M
e, methylene). 2100 (N3). 174
0. 1230 (ester), 1670.154
0 (Aed), 710 (Phenyl). NMR (C
DCl3) δppm: lactose unit; 4.5
8(d, LH, J1.2=8.2Hz, }l-1).
4.67 (d, Ill, J+2=7.9Hz, H-1'
). 5.00 (dd, IH, J2- 3- = 10.
IHz, Il-2') - 5.17 (broad d,
IH, H-4'). 5.25 (dd, IH, J23:
9.4Hz, It-2). Sialic acid unit; 1.89 (
s, 3}! , AcN) - 2.52 (dd, IHvJz
a. 3e"l2-8}1z, J3e.a=4.9Hz,
H-3e), 3.14 (s, 3H, MeO), 4.97
(a+, IN, }I-4). Ceramide unit; 0.88
(t,3H,MeCH2), 1.24(m,24}1,
Me (Ihi) +2). 5.89(dt,l}l,J4.
5=14.4Hz, J5, 6:J5, 6・=7.
1Hz, H-5). Acyl group; 2.00,2. Ql,2
．． Q3, 2.11, 2.15 (5s, 15} 1,5Ac
O) - 7.26 ~ 8.05 (m, 20 N, 4P
h). (7) 0-(methyl 5-acetamide-4,7
-di-Oacetyl-3,5-dideoxy-β-L-arabino-2-heptulopyranocylonate)-(2→3)-
0-(2,4-di-O-acetyl-6-0-penzoyl-β-D-galactobyranosyl)-(I→4)-0-(
3-0-acetyl-2,6-di-O-penzoyl-β10-glucopyranosyl)-(1 −+ 1)-(2S,
3R,4E) -3-0-penzoyl-2-octadecanamido-4-octadecene-1,3-diol (in general formula [1], R=R2=R'=acetyl group, R1=methyl group, R '=R S =benzoyl group, R 6=
-NflCOC1 7H35, compound with n = 12. Hereinafter, it will be abbreviated as compound (1l). ) synthesis compound (9
) 12 (log (78.9 p mol)) was dissolved in 12 ml of a mixed solvent of pyridine and water (5:1), and stirred and reacted at room temperature for 24 hours while blowing apricot sulfide gas. After the reaction was completed, the reaction solution was concentrated. After thoroughly drying the obtained -NH2 body (compound (10)), dichloromethane 6
ml, and add 45 mg of stearic acid (0.16 mg) to this.
III mol) and 36 rag of WSC were added, and the mixture was stirred and reacted overnight at room temperature. After the reaction is complete, 40 portions of dichloromethane are added to the reaction solution for extraction, and the dichloromethane layer is washed with water.
After drying with anhydrous Na2SO4, it was concentrated. The obtained residue was subjected to column chromatography (filling material: Wakogel C-200).
, Eluent: CH2C12/CH30H = 60/1
) to obtain 120 mg of compound (11). Yield 87%.

[α D=+3.9° (C=0.6, Cl{Cl,
). IR v94-(am-') 3350(NH
)-2940.2860 (Me, methylene), 1
740.1230 (ester), 1680, 16
60.1540 (amide). 710 (phenyl). NMR (CDCI3) δppm: Lactose unit; 4,57 (2d, 2H, J+, 2"JI'
, 2=7.9tlz, }I-1.1'). 4.9
9 (dd, IH, }I-2'), 5.18 (m, 2tl
, H-2.4'). Sialic acid unit: l. 68(J11{
, J3m. 3e"J3m. 4=12.4Hz,!-
1-3a), 1.89(s,3}1,^cN), 2.5
3(dd,111,J:le..1=4.6tl
z, If-3e). 3.72 (s, 3H, Men)
, 4.95 (m, IH, H-4), 5.66 (d, LH
, J5. IIH=9-2Hz, NH). Ceramide unit;
0.88 (t, 6N, 2AeC}12). 5.79
(dt, IH, J4.5=14.4Hz, J5.6=
J5,6 =7.11{z,L5).

Acyl group; 1.99, 2.02, 2.03, 2.10
, 2.14 (5s, 15H, 5ACO), 7.30-8
．． 05 (m, 20 H, 4 Ph).

(8) Synthesis of compound (l2) Compound (11) 110+ag (62.4 μm01) was dissolved in 5 ml of methanol, and CH30Na 10
mg was added, and the mixture was stirred and reacted at room temperature for 8 hours. Next, 0.5 ml of water was added to this at 0° C., and the mixture was further stirred and reacted for 4 hours. After the reaction is complete, transfer the reaction solution to Amberlite IR-120.
After filtration, the filtrate was concentrated to dryness and subjected to column chromatography (filling material: Sephadex LH).
-20, eluate: C}IcI3/CI{30H=1
/1) to quantitatively obtain compound (12).

[αko. = +0.46' [C=0.85,
CHCI3/CH3011=1/L (v/v) Ko.

I R y yo H N +''(cm-')
3700-3100 (Off, NH),
2940.2860 (Me, methylene), 1700
(carbonyl), 1640.1560 (amide).

NMR [(CD3)250-D20;98/2co δppm: lactose unit; 4-17(d.LH
, J+. 2=7.5Hz,! {-1), 4.25(d
, 18+ J+ ・. 2 = 8. 0 Hz g
Il-1'). Sialic acid unit; 1.85 (s
, 3H, AcN), 3.04 (dd, LH, 11-3e
). Ceramide unit; 0.85 (L, 6tl, 2MeC
H2), 5.34 (dd, 1tLJ3.4=7.0Hz
, J4. 5=15.4Hz, H-4). 5.52(d
t, IH, J5. a”J5 6r =7.1Hz,H
-5).

Example 2. 0-(5-acetamido-3,5-dideoxyα-D-galacto-2-octulobyranosilonic acid)-(2→3)-0-(β-D-galactobyranosyl)
-(1→4)-0-(β-D-glucopyranosyl)-(
1→l)-(25,3R,4E)-2-octadecanamido-4-octadecene-1,3-diol (general formula [
■In Co, R=acetyl group, R'=R2=R3=R4
=R5=hydrogen atom, R6=-N}lcOcI7H35
Compound with t n=12. Hereinafter, it will be abbreviated as compound (20).

)(1) Methyl (methyl 5-acetamido-4,7
,8-tri10-acetyl-3,5-dideoxy-2-
Thio α-D-galacto 2-octulovyranoside)onate (general formula [■ where R=R”=acetyl group R
l l=R9=methyl group compound. Below, the compound (l
3). ) synthesis of methyl 5-acetamido-4.7.8-tri101acetyl-2-S-acetyl-3,5-dideoxy-2-
Thio α-D-galacto 2-octulopyranosonate 980mg (2.051IIIlo1), CH30N
a 4Bmg (2mIIol) and methyl iodide 1,0
Example 1 using ffI1. The reaction was carried out in the same manner as in (1), and column chromatography [Wakogel C-200.
Eluent: ethyl acetate/n-hexane (5/4)) to obtain 730 mg of compound (13) as syrup.

Yield 82%. [α] o = + 29.7' (C = 0.92,
CI{C13).

NMR (CDCI3) δppm: 1
．． 87-2.15 (5s, 1,511, AcN, 3Ac
O, HeS), 2.75 (dd, 11{, J3m. 3
e42.811Z+J3e. a=4.6Hz). 3
．． 69(dd, IH, J5, 6=10.41{z, J
6. 7=2.4t{z,}l-6), 3.83(s,
3H, MeO), 4.10 (dd, IH, J6. 6=
11.5Hz, J7, B・=7.3Hz, H-8).
4.20 (q+ IH+Ja.s”Js.e”J
s. +n+=10.4}1z, H-5), 4. 5
5(dd, Ill, J7. 6=5.0Hz, It-
8'), 4.87 (ddd, I11, J3-4=11
．． 5Hz, Ito4), 5.29(ddd, III, J
6, ? "2.4HZ, H-7), 5.52 (dd,
IH, NH).

(2) 2-(}limethylsilyl)ethyl O-(methyl 5-acetamido 4.7.8-tri10-acetyl-3.5-dideoxy-α-D-galacto 2-octulopyranocylonate)-(2→3 )-0- (6-0-
Penzoyl-β-D-galactopyranosyl)-(l→4
)-2.6-di-O-penzoyl-β-D-glucobyranoside (hereinafter abbreviated as compound (14)) Compound (13) 690a+g (1.5a+mol)-
2- (}limethylsilyl)ethyl O- (6-
0-penzoyl-β-D-galactopyranosyl)-(1
→4) -2.6-di-0-penzoyl-β-D-glucobyranoside 576B (0.76 mmol) and DMT
Molecular sieves 3A2 containing 1.54 g of ST.
Using 0g, Example 1. Compound (14) 415+ag was obtained by reacting and treating in the same manner as in (2).
Yield 47%. [α]o=1° (C=0.6, CHC13).

NMR (CDCI3) δppm: Lactose unit: 0.88 (w, 2H, Me3Si to C}12
0). 3.57 (m, Ill, Ae3SiCH2C}
I,zO). 4.51 (d, LH, J1, 2=7
．． 7Hz, t{-1), 4.64(d, Ill, J1
．． 2- = 7.9Hz, H-1'). 5.
28(dd, 1}1, J2. 3=8.9Hz,}I
-2). 7.27 ~8.09 (m, 15tl, 3P
h). Sialic acid unit; 1.89 (s, 311, ^cN
), 1.98, 2.05, 2.16 (3s, 9N, 3^
co). 2.67 (ddy 18 g J 3 m.
3e”l2.9Hzg J 3@. 4=4.8HZ
? }l-3e). 3-59 (m, IH, H-6)
, 3.79Cs, 3H, MeO), 4.39(m, IH
, I{-5), 4.98 (m, IH, H-4), 5-1
0(Ill, 1}1,}I-7). 5.35(d,
LH, JsNH"9.5HZ, NO) @ (3) 2-(}limethylsilyl)ethyl O-(methyl 5-acetamido 4.7.8-tri10-acetyl-3,5-dideoxy-α-D-galacto 2 -ocullopyranocylonate)-(2→3)-0-(2.4-di0-acetyl-6-0-penzoyl-β-D-galactopyranosyl)-(I→4)-3-0 one acetyl two,
6-di-0-penzoyl-β-D-glucopyranoside (
General formula [■ where R=R"=R3'=acetyl group R
l t ==methyl group R d J =: benzoyl group, TAS= }limethylsilyl group compound. below,
It is abbreviated as compound (15). ) was added to 200 mg (0.17 mmol) of the compound (14) of Example Process. It was acetylated and treated in the same manner as in (3) to obtain 200 g of compound (15). Yield 90%.

[αkoo"+4.2'" (C=1.2, CIICI:
l).

NMR (CDCI3-CD]00: 1/1)
δppm: lactose unit; 0. 8” (mt.
2H t Me3Sx hi c}120) - 3-5
8 (m+ IHv Me3sirohC}+20). 4
．． 67 (d, 18, J1.2=7.7Hz, H-1),
4.75(d,IH,J1・,26:7.8Hz,H
-1'), 5.03 (m, 2H, H-2', 4'). 5
．． 22 (dd, J, 3=9.4Hz, H-2), 5.4
7 (t.,.h.4"9.4Hz, H-3). 7.3
9-8.09 (n+, 151,3Ph). Sialic acid unit; 1.66 (JILJ3m.3e”J31,4=12
．． 5Hz, H-3a), 2.55(dd t I H
, J 3 @. 4” 4-6}1z l H-3
e). 3. 47 (ddw 18 * J5. 6
"IO-6 FIZ @ J6.7" 2
−61{z + H−6), 4.93(m
, Ill, L4), 5.50 (m, IH, H-7). Acetyl group; 1.92, 2.00, 2.01, 2.02
, 2.12, 2.22 (6s, 18H, 6AcO). (
4) O-(methyl 5-acetamido-4.7.8-triO-acetyl-3,5-dideoxy-α-D-galacto-2-octulopyranocylonate)-(2→3)-0
-(2.4-di-0-acetyl-6-0-penzoyl-β-,D-galactopyranosyl)-(I→4)-3-0
- acetyl-2,6-di-0-penzoyl-β-D-glucopyranose (hereinafter abbreviated as compound (l6)); 240 mg (0.19 nmol) of compound (15);
Example 1. Compound (16) 1 was obtained by treatment in the same manner as in (4).
I got 90+ag. Yield 87%. [αko. =+44.3° (C=0.9, CHCI3
)． I R V ,4i4- (am-')
3500-3100 (OH, NH), 17
40.1220 (ester), 1660. 15
40 (amide), 710 (phenyl). (5) O-(methyl 5-acetamide-4.7.8-
tri-0-acetyl-3,5-dideoxy-α-D-
Galacto-2 octulopyranocylonate) - (2→3)
-0-(2.4-di-O-acetyl-6-0-penzoyl-β-D-galactobyranosyl)-(1→4)-3-
0-acetyl-2,6-di-O-penzoyl-α-D-
Compound (1B) 1, a combination of glucobyranosyl trichloroacetimidate (hereinafter abbreviated as compound (17))
80+ag (0.15 mmol) in Example 1 (5)
Compound (17) 175m(
I got it. Yield 85%. [αko = +41.5@ (C = 0.84, CHC1
y).

NMR (CDCI3) δppm:
Lactose unit; 4.82 (d, LH, J1,2・
=7.9Hz, lI-1'). 5.07 (dd
, 1}1, J2・, 3=9.8Hz, H-2'),
5.29 (dd, IH@Jl. 2”3.7Hz, J2
．． 3"10.2Hz, H-2), 5.85(t, IH
, H-3), 6.67 (d, IH, H-1), 7.27
-8.09 (m, 1511, 3['h). 8.57 (
s, III, C=NII). Sialic acid unit; 1.69
(t,LH,J,a.]*;J3m.4=12.5
Hz, I{-3a), 1.84(s, 3H, AcN)-
2.56 (dd, LH, J3e.4=4.4Hz,
H-3e), 3.46 (dd, IH, J5, 6=10
．． 21{z, J67:2-3Hz, H-6), 3.72
(s, 3H, MeO), 4.85 (m, IH, H-4)
, 5.19 (d, IH, JNH, 5=10.1Hz, N
H). Acetyl group; 1.89, 2.01, 2.02,
2.04,2. L3, 2.23 (f3s, 18H, BA
cO).

(6) O-(methyl 5-acetamide-4.7.8-
Tri-10-acetyl-3,5-dideoxy-α-D-galacto-2-octulovylanocylonate) = (2→3)
-0-(2.4-di-O-acetyl-6-0-penzoyl~β-D-galactobyranosyl)-(1→4) -0
- (3-0-acetyl-2,6-di-0-penzoyl-β-D-glucobylanosyl)-(1→1) - (2
5.3R,4E)-2-azido-3-0-penzoyl-4-octadecene-1.3diol (in the general formula [■], R=R2=R3=acetyl group, R1=methyl group R
4 = R S = benzoyl group, R6 = N3, n = 1
2 compound. Hereinafter, it will be abbreviated as compound (18). ) Synthesis of Compound (17) 170 mg (0.12 mmol) and Compound (10) 107m(, (0.25 tnmol) were reacted and treated in the same manner as in Example 1.(8) to obtain Compound (18). 165 mg was obtained. Yield 81%. [CE] o=-1.82' (C=1.3, C
HC13).

I R v:, 2L"(cm-') 335
0 (NH), 2940.2850 (He, methylene), 2100 (N3). 1740. 12
20 (Sfle> . 1680. 1660.15
30 (7 mid). 710 (7 enyl) NMR (CDC13) δppm: lactose unit; 4.69 (d, IH, J1.2 = 7.5 tlz,
H-1), 4.75<d, INrrv. 2:8.1Hz
, H-1'). 5.03 (dd, LH, H-2').

Sialic acid unit: 1.68 (t, IH, J3., 3*”
J3a. c”12.3Hz, H-3a), 1.83(
s, 3H, ^cN). 2.55(ddy1}1wJ3
s. 4"4-7HzyH-3e), 3.71(s, 3H
, l'leo), 4.84 (m, IH, H-4). Ceramide unit; 0.87 (t,3H,Mec}12).
1.24(m, 24H, Me(cJJi)+2). 5.
66 (td, IN, J4.S”l4-4HZ, J5.
6"J5. 6・=7-2HZtH-5). Acyl group; 1.89, 2.00 (3 冫, 2.10, 2.2
1 (6s, 188, 6^cO), 7.28~8.19
(a+, 20H, 4Ph).

(7) O-(methyl 5-acetamido-4.1.8-
Tri-10-acetyl-3,5-dideoxy-α-D-galacto-2-octulopyranocilone})-(2→3)
-0-(2.4-di〇1acetyl-6-O-penzoyl-β-D-galactopyranosyl)-(l→4)-0-
(3-0-acetyl-2,6-di-0-penzoyl-β
-D-glucobylanosyl)-(1→1)-(2S,31
? , 4g) -3-0-penzoyl-2-octadecanamido-4-octadecene-1,3-diol (general formula [
■] where R=R22R3=acetyl group, R1=methyl group, R4=R5=benzoyl group, R6=-Ntl
COCBH35, compound with n=12. Below, the compound (
19). ) synthesis compound (18) 120mg (
75.3 μmol) in Example 1. After selective reduction with hydrogen sulfide in the same manner as in (7), stearin W
i45o+g (0.16 mmol) and tlsc 36
Example 1 by adding mg. React and process in the same manner as (7),
Compound (19) 128n+g was obtained. Yield 93%.

[αkoo” +11-0” (C=0.56, CH
Cl3). IRv! ! ! ”(cm-') 3
350 (NH). 2940,2860 (Me, methylene), 1740.1230 (ester), 168
0, 1660.1535 (amide). 710
(phenyl). NMR (CDCI3)
δppm: Lactose unit: 4.60 (d, 211
, J1. 2=7.7Hz, It-1). Sialic acid unit; 1.85 (s, 3H, ^cN), 2.56
(dd+IHtJ3a.xe:11.9Hz+J3e
．． a=4.8Hz, II-3e), 3.46(dd,
[1, Jr. 6:10.4H7. , J6, 7:2
．． 611z, H-8), 3.72 (s, 3H, MeO)
, 4.85 (m, IH, H-4), 5.64 (d, lH
, J5, , H=9.3HZ, NH). Ceramide unit;
0.88 (t, 6H, 2MeCH2), 5.77 (d
t, LH, 14.5=15.6Hz, J5.6”J5,
6.=7.8Hz, H-5). Acyl group; 1.94,
2.01 (2), 2.02, 2.11, 2.19 (as
, 18H, 6AcO). 7.27~8.05 (m, 20
H, 4Ph).

(8) Synthesis of compound (20) Compound (19) 99 mg (54μ 01) in Example 1
．． React and treat in the same manner as (8) to obtain compound (20) 62
+g was obtained quantitatively. Cal o=2.65' [C=0.6,CHC
13/CI{301{=1/1(v/v) Co. I R v , j, 44"(c++-' ) 3
700-3200 (0}1,NH), 2940,28
60 (Me, methylene'), 1710 (carbonyl), 1630.1550 (ad). NMR [(CD3)250-020;98/2]
δppm: lactose unit; 4.15 (d, L
H, Jl. 2=8.0Hz,}l-1), 4.22(
d, 18yJl'. 2' = 8.2Hz, H-1')
a Sialic acid unit; 1.90 (s, 311, AcN)
, 2.74 (broad dd, LH, li3e). Ceramide unit; 0.85 (t,6H,2MeCH2),
5.37 (dd, LH, J3. a”1.5Hy., J
a. 5=15.8Hz, 114). s. st
(dj, III, J5.6"J5.6- =
7.51Lz, H-5).

Reference example 2. 0-(methyl 5-acetamide-4.
7,8.9-tetra-0-acetyl-3,5-dideoxy-D-glycerol-α-D-galacto-2-nonulopyranocylonate)-(2→3)-0-(2.4-di0-
acetyl-6-0-penzoyl-β-D-galactobyranosyl)-(l→4)-0-(3-0-acetyl-2,
6-di10-penzoyl-β1D-glucopyranosyl)
-(1→1)-(2S,3R,4E)-2-azido 3
-0-Penzoyl-4-octadecene-1,3-diol (hereinafter abbreviated as compound (25)) (1) 2-(}limethylsilyl)ethyl 0-(methyl 5-acetamide 4.7,8.9 -tetra-0-acetyl 3,5-dideoxy-D-glycerol-α-D-galacto-2nonuropyranocylonate)-(2→3)-
0-(6-0-penzoyl-β-D-galactobyranosyl)-(l→4)-2.6-di0-penzoyl-β-D-glucobyranoside (hereinafter abbreviated as compound (21)).

) synthesis of methyl (methyl 5-acetamide-4.7,8.9
-tetra 0-acetyl-3.5-dideoxy-2-thio D-glycerol α-galacto-2-nonuroviranoside)onate 0.21 g, the compound obtained in Reference Example 1 (
3) Example 1 using 1.14 g of Molecular Sieves 3A containing 0.15 g and 0.88 g of DMTST. Compound (21) was obtained by reacting and treating in the same manner as (2).
0.097g (yield 40%) was obtained. (3) 2-(}limethylsilyl)ethyl 0-(methyl 5-acetamido 4.7,8.9-tetra 0-acetyl-3,5-dideoxy-D-glycerol α-D-
Galacto-2-nonuroviranocylonate)-(2→3)
-0-(2.4-di-O-acetyl-6-0-penzoyl-β-D-galactobyranosyl)-(l→4)-3-0
-Acetyl-2,6-di-0-penzoyl-β-D-glucopyranoside (hereinafter abbreviated as compound (22)) 85 mg of compound (21) was prepared in Example 1 using 8 ml of anhydrous pyridine and 4 ml of acetic anhydride. Acetylated in the same manner as in (3) and treated in the same manner to obtain compound (22) 81mg
(yield 94%).

(4) 0-(methyl 5-acetamide-4.7,8.
9-tetra O-acetyl-3,5-dideoxy-D-
glycerol α-D-galacto-2-oculloviranocylonate)-(2→3)-0-(2,4-di-0-acetyl-6-0-penzoyl-β-D-galactobyranosyl)-( 1→4)-3-0-acetyl-2.6-di0-
A combination of penzoyl-β-D-glucopyranose (hereinafter abbreviated as compound (23)), 666 mg of compound (22), was added to Example 1. Compound (23) 499+g (yield 8
0.9%) was obtained.

(5) O-(methyl 5′-acetamide-4.7,8
．． 9-tetra-0-acetyl-3,5-dideoxy-D
-glycerol α-D-galacto-2-nonuroviranocylonate)-(2→3)0-(2.4-di-0-acetyl-6-0-penzoyl-β-D-galactopyranosyl)
-(l→4)-3-0-acetyl-2,6-di0-benzoyl-α-D-glucopyranosyl trichloroacetimidate (in general formula [■b, R=R2'=R"=
Example 1 499 mg of compound (23), 1.2 ml of trichloroacetonitrile, and 32 mg of DB0 were prepared by combining 499 mg of compound (23), 1.2 ml of trichloroacetonitrile, and 32 mg of DB0. ．．
React and treat in the same manner as (5) to obtain compound (24) 52
2 mg (yield 93.9%) was obtained. [αko=+41.84' (C=0.76, Cfi
C13).

IRv! iA"(c1') 3700-31
50 (NH), 3150-2800 (CH), 1
740. 1230 (ester). 1680.1
540 (amide). 720 (phenyl).

NMR (CDCl3) δppra: sialic acid unit; 3.71 (s, 3H, MeO), 2.59 (dd
, LH, J3m. 3e”13.37Hz, J3@,
4:4.76Hz, H-3e). Lactose units; 8
．． 55 (s, ltl, C=NH), 6.66 (d, IH
, J+, 2=3.67Hz, }I-1), 7.43
~8.06 (m, 15H, 3Ph). Acetyl group; 1
．． 84, 1.97, 2.00, 2.01, 2.04, 2
．． 06, 2.13, 2.21 (8s, 24H, 7AcO
, AcN).

(6) 0-(methyl 5-acetamide-4.7,8.
9-tetra-0-acetyl-3,5-dideoxy-D-
Glycerol alpha 101 galacto 2-nonuroviranocylonate)-(2→3)-0-(2.4-di-0-acetyl-6-0-penzoyl-β-D-galactopyranosyl)
-(l→4)-0-(3-0-acetyl-2,6-di-0-benzoyl-β-D-glucobylanosyl)-(l→
1) -(2S,3R,4E)-2-azido-3-0-pen-zoyl-4-octadecene-1,3-diol (hereinafter abbreviated as compound (25)); compound (24) 504 mg; Compound (10) 310
Example 1 using mg. React and treat in the same manner as (6) to obtain compound (25) 552 mg (yield 92.0%)
I got it.

CaE o=−2.79” (C=0.57,
CHC13) -IR y! A4-(cm-')
3700-3150 (NH), 3150-2800 (
CH), 2100 (N3) - 1740. 12
30 (ester). 1860,1540 (amide) + 710 (phenyl). NMR (CD
C13) δppm: sialic acid unit; 5.2
6 (d, LH, Js.N.4"10.26Hz, NH)
- 4.86 (n, LH, H-4). 3.70s, 3
}1, MeO), 2-58 (dd, IH, J3m. 3
*”12.64Hz, J3@, 4=4.58Hz, H
-3e), 1.68 (t, IH, H-3a). Lactose units; 8.07-7.35 (+n, 20 ft, 4
Ph), 5.26 (dd, LH, J+. 2 = 7.88
Hz, J2, 3=9.5311z, H-2). 5
．． 04 (dd, IH, J1-.2・=7.88FI
z, J2-, 3=L0.07Hz, H-2'), 5
．． 00 (broad d, IH*H-4'), 4.89
(d, IH, J12=7.88Hz, H-1'). 4
．． 70 (d, LH, H-1), 4.61 (dd, ill
, J3. a; 3.30Hz, H-4'). 2.21,
2.12, 2.03, 2.03, 2.02, 2
．． 00, 1. 99.1. 84 (8s, 24H, 7
AcO, ^cN). Ceramide unit; . 5.68(dt
,II(,J4.s=14.11tlz,J,.6
:J5. 6=7.051Iz, H-5).

Example 3. 0-(5-acetamido-3,5-dideoxy-D-glyceroα-D-galacto-2-nonuropyranosilonic acid)-(2→3)-0-(β-D-galactopyranosyl)-( 1→4)-0-(β-D-glucopyranosyl)-(l→1)-(2S, 311.4g)-2
-acetamide 4-octadecene-1,3-diol (in the general formula [1 [[], R=acetyl Go, R1=R2
=R'=R'=RS=hydrogen atom, R7= -NHC
OCI{ 3, compound with n=12. Below, compound (27
). ) Synthesis (1) 0-(methyl 5-acetamide-4.7,8.
9-tetra O-acetyl-3,5-dideoxy-D-
Grise-α-D-galacto-2-nonuroviranocylonate)-(2→3)-O-(2.4-di-0-acetyl-6-0-penzoyl-β-D-galactopyranosyl)-( 1→4)-0-(3-0-acetyl-2,6-di-0-benzoyl-β-D-glucopyranosyl)-(
1→1)-(2S,3R,4E)-2-aceto-do-3-0-penzoyl-4-octadecene-1,3-diol (in general formula [I11], R=R2=R3=acetyl group, R'=methyl group, R'=R, 5=benzoyl group,
R7: -NHCOC}13, a compound where n = 12. Hereinafter, it will be abbreviated as compound (26). ) Synthesis of Compound (25) obtained in Reference Example 2 100 mg (60 μm
ol) in Example 1. In the same manner as in (7), the amine (hereinafter abbreviated as compound (27)) was selectively reduced with hydrogen sulfide.
) and acetylated by adding acetic anhydride 2III1 to give Example 1. Treated in the same manner as (7), compound (2
6) 93 mg was obtained. Yield 92%. However, the eluent for column chromatography is #ethyl acid/n-hexane=
471 was used.

[α]o=+13.5° (C=0.56, CHCl
3) -NMR (CDCI3) δρpm: La1
Cutose unit; 4,63 (d, LH, Jl, 2=7
．． 5Hz, H-1). 4.84(d,LH,J,-
, 2- = 7.9Hz, }I-1'), 4.99(m
, 2H, H-2', 4'), 5.18 (dd, 1B, J
2, 3=9.5Hz, H-2). Sialic acid unit; 2
．． 56 (dd, IH, J3m.3e=12.5Hz, J
x. 4"4.8Hz, H-3e). 3.72(s, 3
}1, NeO), 4.90 (m, IH, H-4). Ceramide unit; 0.88 (t,3}1,MeCH2),
5.76(dt, LH, J,. 5=14.4}1z,
J5. 6"JS. 6' = 7.2Hz, H5). Acyl group; 1.82, 1.90 (2), 2.00 (2)
, 2.02 (2), 2.11, 2.18 (9s, 271
1,7^cO,2AcN). (2) Synthesis of compound (27) 85 mg (50 pmol) of compound (26) was dissolved in 4 ml of methanol, and 17 mg of CH30Na was added to this.
was added, and the mixture was stirred and reacted at room temperature for 5 hours. Next, add 0.0% water to this. 5 ml was added at 0°C, and the reaction was further stirred for 5 hours. After the reaction is complete, add Amberlite IR-12 to the reaction solution.
After filtration, the filtrate was concentrated to dryness.
Column chromatography (filling material: Sephadex L)
}I-20, eluent: C}130H),
47 mg of compound (27) was obtained. Yield 97%. [a] o= +o. e” [(= 1.0, C
HCl3/CH30H"l/1 (v/v)]. NMR (CDCI3-CD30D;l/1)
δppm: lactose unit; 4.31 (d, IH,
JI, 2==7.5Hz, H-1), 4.44(d,
LH, J1-. 2-=7.2Hz, H-1'). Sialic acid unit; 2.86 (dd, IH, J3m, 3*:1
2. SHz, J3@. 4=4.7Hz, }I-3e)
, ceramide unit; 0.89 (t,3H,211qC}
12), 5.46 (dd, IH, J3. 4”7.1f
{z, J4. 545. 4Hz, H-4). 5
．． 70 (dt., LH, J5, 6-15. 6=
7. ltlz, H-5). Acyl group; 1.96,2
．． 04 (2s, 6tl, 2AcN).

Example 4. 0-(5-acetamido-3,5-dideoxy-o- Chryserow α-D-galacto-2-nonuroviranosilone rIl)-(2→3)-0-(β-D-
Car-y') Toby-y/Sil)-(1→4)-0
-(β-D-glucopyranosyl)-(1→1)-(25
, 3R, 4E)-2-[(RS)-2-hydroxytetradecanamide-4-octadecene-1,3-diol (in the general formula [■, R=acetyl group, R'=R2=
R3=R'=R5=hydrogen atom, R7=-NHCOCH
(OH)C+zH2st n=12 compound. Hereinafter, it will be abbreviated as compound (29). ) synthesis (1) 0-(methyl 5
-acetamido-4.7,8.9-tetra-0-acetyl-3,5-dideoxy-D-glycerol-α-D-galacto-2-nonuroviranocylonate)-(2→3)0-
(2.4-di-0-acetyl-6-0-penzoyl-β
-D-galactobyranosyl)-(l→4)-0-(3-
0-acetyl-2,6-di-0-penzoyl=β101 glucopyranosyl)-(1→1)-(2s,3R,4E
)-2-C(RS)-2-acetoxytetradecanamide]-3-0-penzoyl-4-octadecene-1,3
one diol (in the general formula [m], R=R2=R3=acetyl group, R1=methyl group, R'=R5=benzoyl group,
R7=-NIICOCH(OCOCJ)C+2H2s
compound. Hereinafter, it will be abbreviated as compound (28). ) Synthesis Example 3. Compound (27) obtained in (1) (Compound (2)
5) (RS)-2-acetoxytetradecane fil (combined from 100B (60 pmol))
Example 1 by adding 34B (0.12 mmol) and %lSC 35B. The reaction and treatment were carried out in the same manner as in (7), and the compound (
28) 103 mg was obtained. Yield 90%. However, as the eluent for column chromatography, ethyl acetate/n-hexane = 371 was used.

[αko. = +10.7"(C"0.66, CH
C13).

NMR (CDCl3-CD30D) δpp:
Lactose unit; 4.84 (d, IH, Jl, 2”
8.4Hz, H-1), 5.01(d, LH, J12・
=8.3Hz, H-1'), 5.21(t, IH, J2
, 3=8.5Hz, H-2).

Sialic acid unit; 1.83 (s, 3H, AcN), 2.
56 (dd, IH, J3,, 4=4.8flz, H-
3e), 3.71(s, 3H, Neo). Ceramide unit; 0.88 (tt6H, u匡CH2). Acyl group;
1.89, 1.98, 1.99, 2.00, 2.02,
2.11, 2.14, 2.18 (8s, 24H, 8^c
O), 7.26-8.06 (+, 20 H, 4Ph).

(2) Synthesis of compound (29) Compound (28) 90m+c (47 μmol) was prepared in Example 3. Compound (29) 53m was treated in the same manner as (2).
I got g. Yield 98%.

[αko=+1.5” [C=L Ct-ICl
3/CH30)+=l/l(v/v)co.

I R v,4Q4m(Cm-') 3400
(Oll, Nll). 2940, 2860
(Ae, methylene) + 1710 (kanoreboninore), 1630.1550 (amide).

NMR (CDCI3-CD30D=1/1)
δppm: lactose unit; 4.31 (d, 18
, J,, 2=7.9Hz, H-1), 4.33(d,
1Mr J). 2 ・= 7. 5 tl Z +
H-1') @ sialic acid unit; 2.03
(s, 3H, AcN), 2.86 (dd, IH, J3g
．． 3e"12.2Hz, J3e, 4=4.7}1z
, H-3e). Ceramide unit; 0.89 (t., 6H
, liicH2), 4.96(dd,].H,H-4)
, 5.73 (dt, LH, J4.5:l5.OHz
, J5. 6=J'+6・=7.5Hz, H-5).

Example 5. 0-(5-acetamido-3.5-dideoxy10-glycerol α-D-galacto-2-nonulopyranosilone a)- (2-+ 3)-0- (β-
D-galactopyra/cy#)-(1→4)-0-(β-D-glucopyranosyl)-(l→1)-(25,3R,
4E) -2-[(R)-3-Hydroxytetradecanamidoco-4-octadecene-1,3-diol (in general formula [I11], R=acetyl group, R'=R2=R3
=R'=RS=hydrogen atom, R7=-NHCOCR2C
}I(OH)CzH23+ Compound where n=L2. below,
It is abbreviated as compound (3l). )'s joint precept (1) 0-(methyl
5-acetamido-4.7,8.9-tetra-O-acetyl-3,5-dideoxy 101 glycerol-α-D-galacto-2-nonuroviranocylonate)-(2→3)-
O-(2.4-di0-acetyl-6-0-penzoyl-β-D-galactopyranosyl)-(1→4)-0-(
3-0-acetyl-2,6-di-0-penzoyl-β-
D-glucopyranosyl)-(1→1)-(2S,3R,
4E)-2-[(R)-3-acetoxytetradecanamide]-3-0-penzoyl-4-octadecene-1.
3 diol (in the general formula [m], R=R2=R3=acetyl group, R1=methyl group, R'=R5=benzoyl group,
R7-NHCOCH2CH(OCOCH3)C++l
I23, compound with n = 12. Hereinafter, compound (30)
It is abbreviated as ) Example 3. Compound (27) obtained in (1)
) (combined from compound (25) 90B (54 p mol)) was added with 28IIg of (R)-3-acetoxytetradecanoic acid and WSC 31B to prepare Example 1. (
Compound (30) 90mz was reacted and treated in the same manner as in 7).
I got it. Yield 89%.

[a] o= +9.1° (C=0.44, C
HC13) -NMR (CDCI3-CD30D=1
/1) δppm: lactose unit; 4.88
(d, ill, Jl, 2:7.9}1z, II-1)
, 4.85 (d.111sJl・.2・=7.9Hz,
H-1'), 4.99 (m, 2tl, tl-2', 4'
), 5.12(dd, l}I, J2. 3=9.9t
lz, H-2). Sialic acid unit; 1.64 (tllH
, J3m. 3e=J3m. 4=12.5Hz, H-
3a), 1.83 (s, 3H, AcN), 2.56 (d
d,1}1,J3g. 4”4.8Hz, H-3e),
3.72 (s, 3H, AEO). Ceramide unit; 0.
88 (t, 6H, 4JLtCHz). 5.75 (dt
, IHj4. 5”l5-4Hz, J5, 6”JS.
6' = 7.5Hz, H-5). Acyl group; 2.0
0(2), 2.01(2), 2.02(2), 2.12
,2.18(8s,241{,8AcO),7.26-
8.06 (m, 20 H, 4 Ph). (2) Compound (
3l) 80 mg (43 p mol) of compound (30) was added to Example 3. Compound (31) 50m was treated in the same manner as (2).
g was obtained quantitatively. [α o = -0.6' [C
=1, CHC13/CH30H=1/1 (v/v).

I R v,! ．． H- (cod-') 35
00-3300 (OH, NH), 2940, 2850
(Me, methylene). 1710 (carbonyl)
, 1650.1550 (amide).

NMR (CDCI3-CD30D=1/1)
δpp 12 lactose units; 4.32 (d, LH,
J+. 2:7.7HZ,H-1), 4.44(d,0
1, J12- = 7.71 {z, H-1'). Sialic acid unit; 2.04 (s, 3H, AcN), 2-8
8 ( d d * l } l t J ] a.
3 g ” 10 - 6 Hz t J 3 g
, 4 = 4. 5 Hz tH-3e). Ceramide unit; 0.89 (t, 6H, 2MeCHz). 5.
46 (dd, I11, J34=7.111Z, J45
=15.6Hz, +{-4). 5.70 (dt, 1
H y J5. 6”J 5. 6.”7. 5Hz
v H-5) eExample 6. 0-(5-acetamido-3,5-dideoxy-D-glycerol α-D
-galacto-2-nonuroviranosilonic acid) -(2→3)
-0-(β-D-galactobyranosyl)-(1-)4)
-0-(β-D-glucobi-7/sil)-(1→1
)-(2RS)3-(2-tetradecylhexadecaneamide)-1,2-propanediol (general formula [IV]
where R=acetyl group # R'=R2=R3=R'=R
S=hydrogen atom, R8: -CH(CI4H2Q)2 compound. Hereinafter, it will be abbreviated as compound (34). ) Synthesis (1) 0-(methyl 5-acetamide-4.7,8.
9-tetra-0-acetyl-3,5-dideoxy-D-
Grise-alpha-D-galacto-2-nonuroviranocilanotone-(2→3)-O-(2,4-di-O-acetyl-6-0-penzoyl-β-D-galactopyranosyl)
-CL→4)-0-<3-0-7cetyl-2,6-di0-benzoyl-β-D-glucopyranosyl)-(1→
1)-(2RS)-2-0-penzoyl-3-penzyloxylponylamino-1,2-propanediol (
In the general formula [■], R=R2=R3==acetyl group, R
'=methyl group, R'=RS=benzoyl 2E I R
8" Penzyloxy Go compound. Hereinafter, Compound (24) obtained in Synthesis of Compound (32) Reference Example 2 150 mg (0.11
mmol) and (2RS)-2101penzoyl-3-penzyloxycarbonylamino-1,2-propanediol 74B (0.22 mmol) were dissolved in 3+ ul of vi-dried dichloromethane, and added with molecular sieves 4A AM- 300 type (MS-4A-AV-30
0) Add 1.4g of ether, stir at room temperature for 30 minutes, cool to 0°C, and add 30ml of BF3-diethyl ether.
g was added and stirred at the same temperature for 4 hours. After the reaction was completed, dichloromethane was added to the reaction solution for extraction, and the dichloromethane layer was washed with aqueous sodium bicarbonate and water, dried over anhydrous Na2SO4, and concentrated. The obtained syrup was subjected to column chromatography (filling material: Wako Gel C-200, eluent: #ethyl acid In-hexane = 3/1) to obtain compound (32) 1
42 mg was obtained. Yield 85%. C (L) o= +
7.0° (C=0.9, C}ICI3). N M
R (CDCI 3 ) δppm: Lactose unit; 4.60 (d, LH, Jl. 2 = 9.0H
z, H-1), 4.64 (d, LH, JV2・=8.2
11z, II-1'). 5.20(t,Ill,J+
．． 2=J2. 3=9.011z, II-2). 5
．． 45(near t,}I-3). Sialic acid unit;
1.63(Ser I H y J 3 a]e”J3m
, 4=12.5}1z,}l-3a), 1.82(s,
3H, AcN), 2.56 (dd+IH+J3c.4=
4.7Hz, H-3e), 3.59(broad d,
IH, J67=2. O}Iz, J7.6=8.8Hz,
H-7), 3.71(s,3H,)4eO). 4.85
(m, IH, H-4), 5.33 (dd, LH, J6.
7"2.0I{Z, J7.8"8.8Hz, H-7),
5.48 (a+, LH, }I-8). Acyl group; 1.
98, 1.99, 2.00, 2.02, 2.07, 2.
12, 2.21 (7s, 21H, 7AcO). 7.22
~8.05(■,25}1.5Ph). (2) 0-(methyl 5-acetamido-4.7,8.9-tetra0
-acetyl-3,5-dideoxy-10-glycerol-α-D-galacto-2-nonulopyranocilone}) -(2→
3) -0-(2.4-di-O-acetyl-6101penzoyl-β-D-galactopyranosyl)-(1→4)-
0-(3-0-acetyl-2,6-c-Q-henzoyl-β-D-glucopyranosyl)-(1→1)-(2RS
)-2-0-penzoyl-3-(2-tetradecylhexadecaneamide)-1,2-propanediol (in general formula [IV], R=R2=R'=acetyl group, R1=methyl group I R' =R5=benzoyl group, R8=-CH(
Compound of Cl4829)2. Hereinafter, it will be abbreviated as compound (33). ) Synthetic compound (32) 100mz (64 it mol) was dissolved in ethanol 5Il11, and 10% Pd-
C catalyst 60 mg and vinegar aO. 2 ml was added and hydrogen gas was introduced at room temperature for 2 hours. After the reaction was completed, the catalyst was filtered off and concentrated, and 3 ml of dichloromethane and 1.4 ml of dichloromethane were added to the resulting residue.
-Dioxane III11 was added and dissolved. 2 to this
-Tetradecylhexadecane* 57mg and WSC
After the reaction was completed, dichloromethane was added to the reaction solution for extraction, and the dichloromethane layer was washed with aqueous sodium bicarbonate and water, dried with anhydrous Na2SO4,
Concentrated. The resulting syrup was subjected to column chromatography (filling material: Wakogel C-200, eluent: CHC
I3/CH30+1=50/1) to give compound (33
) 84 IQg was obtained. Yield 71%.

[αko o= +6.2' cc=o. sg,CHC
13].

NMR (CDCI3-CD30D=1/1)
δppm: lactose unit; 4.73 (d, IH
, J+. =7.7Hz, H-1), 4.91(d,1
8+J+. 2=7.7Hz, 11-1'), 5.20(
t,J,,3=8.2HZ,H-2),5.49(Jin,
18, H-3). Sialic acid unit; 1.63 (t., L
H, J,]e”J1a4=12.21+z,11-3a
), t. 82 (s.311, AcN), 2.57 (dc
LILJ3e. 4=4.6Hz, H-3e), 3.7
2(s,3H,AeO), 4.81(m,LH,}I
-4). 5.34 (dd, LH, J6.7”2.7HZ
, J7. e"8.9Hz, H-7), 5.48(m, 1
1 {, H-8). Lipophilic group; 0.88(t,6B,2
NeCHz), 1.26 (S, 5211, 26CH2)
. Acyl group; 1.97, 1.99, 2.01, 2.1
2 (2), 2.20, 2.22 (7s, 21H, 7Ac
O), 7.20-8.06 (+i, 20H, 4Ph).

(3) Synthesis of compound (34) 83 mg (44 it mol) of compound (32) was added to Example 3. Process in the same way as (2). Compound (34) 50
mg was obtained quantitatively.

[a] o=-5.0@[C=0.9, CHC13
/CH30H:1:1]-I R VW! A (am
-') 3700-3350 (OH, NH). 2
940,2850 (Me, methylene), 1700
(carbonyl), 1630.1540 (amide).

NMR [(CD3)250-D20;98/2]
δPP+ll: lactose unit; 4.16 (d, I
H, Jl. 2=7.911z,H-1), 4.20(
d, IH, Jl-. 2-:8. IHZ, H-1')
,1 sialic acid unit; 1.89 (5138, AcN)
, 2.75 (dd, LH, J3a. 3e=12.2H
z, J3e. a=4-6Hz, H-3e). Lipophilic group; 0.85 (t,6H,2MeCl{2). 1.2
3(m, 52H, 26Cl{2). Example 7. 0-(5-acetamido-3,5-dideoxyD-glyceroα-D-galacto-2-nonuroviranosilonic acid)-(2→3)-0-(β-D-galactopyranosyl)-(l →4)-0-(β-D-glucobylanosyl)-(1→1)-3-(2-tetradecylhexadecaneamide Ll-propanol (in general formula [V], R=acetyl group, Rl=R2 : R 3 ==
R 4 = hydrogen atom, R 8: -CH(CIlI82
9) Compound 2. Hereinafter, it will be abbreviated as compound (37). ) or (1) 0-(methyl 5-acetamide 4.7,8
．． 9-tetra-0-acetyl-3,5-dideoxy-D
-Grise-α-0-galacto-2-nonuroviranocylonate)-(2→3)-O- (2. 4-di-0-acetyl-6101penzoyl-β-D-galactobyranosyl) -(1→4)-0-(3-0-acetyl-2,6
-D-0-penzoyl-β-D-glucopyranosyl)=
(1→1)-3-penzyloxycarbonyla main No. 1
-Probanol (R=R2=R' in the general formula [V]Gm
=7 cetyl group, R'=methyl group, R4=benzoyl group,
A compound in which R 8 =penzyloxy group. Below, the compound (
35). ) or Compound (24) obtained in Reference Example 2 200 mg (0.14
3IIIlol), 3-penzyloxycarbonylamino-l-propano? 60mg (0.3mm
ol), Molecular Sieves 4AAW-300 type (85-4A-AM-300) 1.8g and BF3
- Using 40 ml of diethyl ether, Example 6A1)
React and treat in the same manner as above to obtain 182 mg of compound (35)
I got it.

Yield 88%. [(X] o=+5.2” (C=0.58,
CHCh).

NMR (CDCl3) δppm: Lactose unit; 4.61 (dd, ILJ2・3:13.6tlz
, J3. a: 3.6Hz. }l-3'), 4.6
3 (d, LH, J+. 2”7.311Z, H-1).
4.89 (d, LH, J+■=7.9}1z,}l-
1'), 5.19 (dd, IH, Jz3:9-5Hz,
H-2), 5.49 (t, IH, J3.4=9.5H
z, H-3). Sialic acid unit; 1.83 (s, 3H,
AcN), 2.57 (ddtlLJ3m. 3e=12
．． 5Hz, J3c4=4.6Hz, H-3e), 3.7
0(s,3H,MeO), 4.87(++,IH,H-
4), 5.19 (d, IH, J,. N14”lO.3
HZ, NH), 5.35 (dd, IH, J6■: 2.8
Hz, J7. e”8.9Hz+H-7), 5.55(
m,111,H-8)-acyl group; 1.97,2.0
0, 2.01 (2), 2.02, 2.12, 2.22 (
7s, 218, 7AcO), 7.27-8.06 (m,
20H, 4Ph). (2) 0-(methyl 5-acetamido-4.7,8.9-tetra 0-acetyl-3,5
-Dideoxy-D-glycerol α-D-galac. Toh 2
1nonuropyranosilone})-(2→3)-O-(2.
4-di-0-acetyl-6-0-penzoyl-β-D-
Galactobyranosyl)-(1→4)-0-(3-0-acetyl-2,6-di-0-penzoyl-β-D-glucopyranosyl)-(1→1)-3-(2-tetradecylhexadecaneamide) -1-propanol (general formula [V]
In , R = R 2 = R 3 = acetyl group, R
'=methyl group, R4=benzoyl group, R8=-CH(
C141129)2 compound. Hereinafter, it will be abbreviated as compound (36). ) Synthetic compound (35) 80 mg (50 μmol) was dissolved in 5 ml of ethanol and 60 lIlg of 10% Pd-C catalyst
Example 6. Hydrogen gas was introduced and reacted in the same manner as in (2). 2- to the obtained amine
Tetradecylhexane a somg and WSC 32m
Example 6. Compound (36) 12 (+g) was obtained in the same manner as in (2). Yield: 73%
.

[αco o=+1.0' cc=o. a, CI
lCl3]. NMR (CDCI3-CD30D=1/
1) δppm: lactose unit; 4.63 (
dd, III, J2. x”10.5Hz, J34=3
．． 5HZ. 83′), 4.64(d,ill,J,,
2=7.911z, LL). 4.98 (d, LH, J
2:8.21Iz, II-1'), 5.17(dd,
IH, J2. 3=9.51{z, tl-2), 5.5
0(t., IH, J2.3”J3.4”9.5HZ,H
-3). 7.31-8.06 (m, 151{, 3Ph)
. Sialic acid unit; 1.82 (s, 3H, AcN), 2
．． 5 7 ( d d g l } I t J 3 m
, 3 @ :13. 1Hz + J3e
4=4-3HzrH-3e)
, 3.71 (s, 3H, MeO), 4.89 (m, IH
, H-4), 5.33 (dd, If{, Js7=2.
4Hz, J7.6=9.5Hz, H-7), 5.50(
+1, IH, II-8). Lipophilic group; 0.88 (m,
6H,2MeCH2). 1.25 (s, 5211,
26CH2).

Acetyl group; 1.99, 2.00, 2.01 (2),
2.03, 2.13, 2.22 (7s, 21tl, 7A
cO).

(3) Synthesis of compound (37) 70 mg (40 μmol) of compound (36) was added to Example 3.
．． The mixture was treated in the same manner as in (2) to quantitatively obtain 45 mg of compound (37).

[α] o=5.8' [C=0.9,
CHCl3/CH30H4:1]-I R v? A (am-') 3700-3400 (Off
, NH), 2940.2850 (Me, methylene)
, 1700 (carbonyl), 1620.1560 (
amide).

NMR [:(CD3)250-D20=98/2]
δppm: lactose unit; 4.17(d,1}
1, J+. 2=8. Ol1z, H-1), 4.21(
d, LH, J12:8.3HZ, H-1′). Sialic acid unit; L. 90 (S, 3H, AcN), 2-75 (dc
L11LJ3+3e=12.511z, J3c. 4=
4.611z, It-3c). Lipophilic group; 0.85 (
t,611,2MeCll2), 1. 23 (m,
521{,26C}l2).

[Effects of the Invention] The present invention provides novel gangliosides in which the carbon chain of the sialic acid moiety and the lipophilic group in the ceramide moiety of gangliosides are variously modified, and novel intermediates thereof, thereby improving the chemical structure of gangliosides. This invention makes it possible to study the relationship between bio-burial activity and has a remarkable effect in expanding the scope of the search for useful gangliosides.

Patent applicant: Wako Pure Chemical Industries, Ltd.

Claims (3)

[Claims] (1) Compounds represented by the general formula [I], [II], [III], [IV] or [V] ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ [I] [In the formula, R^ is fat represents an acyl group of the group, R^1 represents a hydrogen atom or a lower alkyl group, R^2, R^3,
R^4 and R^5 both represent a hydrogen atom, or each independently represents an acyl group, and R^6 is -N_3, -NH
_2 or -NHCORa (however, Ra has 1 to 30 carbon atoms
represents a saturated or unsaturated alkyl group, which may be linear or branched. ), and n represents an integer from 0 to 20, provided that when R^1 is a hydrogen atom, R^2~R
Each of ^5 represents a hydrogen atom, and when R^1 is a lower alkyl group, R^2 to R^5 all represent an acyl group (which may be the same or different). ] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] [In the formula, R, R^1, R^2, R^3, R^4, R^5
, R^6 and n are the same as above, however, when R^1 is a hydrogen atom, R^2 to R^5 all represent hydrogen atoms,
When R^1 is a lower alkyl group, R^2 to R^5 all represent an acyl group (which may be the same or different). ] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [III] [In the formula, R^7 is -NHCOCH_3, -NHCOCH
(Ra)Rb or -NHCOCH_2CH(Ra)Rb
(However, Rb represents a hydroxyl group or an acyloxy group, and R
a is the same as above. ), R, R^1, R^2, R
^3, R^4, R^5 and n are the same as above. However, when R^1 is a hydrogen atom, R^2 to R^5 all represent a hydrogen atom, and when R^1 is a lower alkyl group, R^2 to R^5 are all acyl groups (each other may be the same or different), and R^7
is -NHCOCH(Ra)Rb or -NHCOCH_2
CH(Ra)Rb, and when Rb is a hydroxyl group, R
^1 to R^5 are all hydrogen atoms. ] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [IV] [In the formula, R^8 is a saturated or unsaturated alkyl group having 1 to 30 carbon atoms (which may be linear or branched). ) or represents a benzyloxy group, R, R^1, R^2, R^3
, R^4 and R^5 are the same as above, except that when R^1 is a hydrogen atom, R^2 to R^5 all represent a hydrogen atom, and when R^1 is a lower alkyl group, R ^2 to R^5 all represent an acyl group (they may be the same or different), and when R^8 is a benzyloxy group, R^1 to R^5 are All represent acyl groups (which may be the same or different). ] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[V] [In the formula, R, R^1, R^2, R^3, R^4 and R^
8 is the same as above. However, when R^1 is a hydrogen atom, R^
2 to R^4 all represent a hydrogen atom, and when R^1 is a lower alkyl group, R^2 to R^4 are all acyl groups (they may be the same or different). represents. Also, when R^8 is a benzyloxy group, R^
1 to R^4 all represent an acyl group (which may be the same or different). ] (2) A compound represented by the following general formula [VI] or [VII]. ▲There are mathematical formulas, chemical formulas, tables, etc.▼[VI] (In the formula, TAS represents a trialkylsilyl group, and R^
1'2R^2', R^3' and R^4' represent an acyl group, and R is the same as above. ) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [VII] (In the formula, R, R^1', R^2', R^3', R^4'
and TAS are the same as above. ) (3) A compound represented by the following general formula [VIII] or [IX]. ▲There are mathematical formulas, chemical formulas, tables, etc.▼[VIII] (In the formula, R^9 represents a lower alkyl group, R, R^1
' and R^2' are the same as above. ) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [IX] (In the formula, R, R^1', R^2' and R^9 are the same as above.)