JPH0372491A - Sugar chain-related antigen derivative - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R<1> is 3-300 alkyl; R<2> is lower alkanoyl). EXAMPLE:Propyl 2-acetamide-3-0-(alpha-L-fucopyranosyl)-4-0-[2-O-(alpha-L- fucopyranosyl)-beta-D-galactopyranosyl]-2-deoxy-beta-D-glucopyranoside. USE:A tumor marker. PREPARATION:A glucosamine synthetic element of formula II and a galactose synthetic element of formula III are mutually bound to form a compound of formula IV. Thence, two molecules of fucose synthetic element of formula V are bound to the above compound.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention is directed to oligosaccharide derivatives, more specifically fucosyl SSEA (stage-
specific embryonic antige
n) Concerning new derivatives of the -1s or Le' antigen.

[Conventional technology]

Due to advances in basic research on sugar chain abnormalities that occur as cells become cancerous, sugar chain antigens have been in the spotlight as tumor markers in recent years. One of such sugar chain-related antigens is the following formula (n) Fuccr 1-+ 2 Gaiβ1-4 GJ2c
NAcβ1-↑ Fuccr1 3Galβ1--4Gj! c β1-+Cer
The sugar chain structure represented by (II) (hereinafter referred to as rLe' J) has extremely high cancer specificity, and antigens having this sugar chain structure are extremely sensitively reflected in the body fluids of cancer patients.
In addition, specific antibodies that can recognize the sugar chain structure have been established, making them extremely useful as cancer screening and cancer diagnostic materials (CancerRes, 46.
2619-2626 (1986); Bioche
m, Biophys.

Res, Commun, , 100.1578-15
86 (1981); J, Biol, CheaI
, .

259, 4672-4680 (1984); J.
Rial, Chem, 258.11793-1
1797 (1983); Cancer Res, ,
43.5489-5492 (1983) etc.].

[Problem to be solved by the invention]

However, there are several problems with the preparation of Le' and the specific antibodies therefor. That is, a purified antigen is required to prepare a Le'-specific antibody, and when measuring a tumor marker using the specific antibody,! There is a need for purified antigens that can be used as antigens or insolubilized antigens or standard antigens, but isolating and purifying such purified antigens from living organisms requires complicated steps, yields are small, and costs are high. There is a problem.

In addition, Le' can also be prepared by synthetic chemical means, but there is a problem in that the yield of the step of bonding the ceramide (Cer) moiety in its structure to the sugar chain moiety is extremely low [Ca
rbohydrate Re5earch, 155(1
986).

C1-C5; 156 (1986), CI-C5;
162 (1987), 237-246].

Therefore, Le' is chemically homogeneous, can be produced efficiently in large quantities, and has antigenicity equivalent to natural Le'.
The development of Y derivatives has been desired.

[Means to solve the problem]

As a result of intensive research in order to solve the above problems, the present authors have found that among the sugar chain structures of formula (II), Fucαl-+2
Gaj! β1-46I! The present invention was completed by discovering that a chemically modified partial structure of cNAc↑Fucαl exhibits antigenicity similar to that of Lema and is easy to synthesize.

That is, the present invention is based on the following general formula (I) [wherein R1 represents an alkyl group having 3 to 30 carbon atoms, R
a represents a lower alkanoyl group] (hereinafter referred to as "Lev derivative").

In the general formula (I) representing the L e Y derivative of the present invention, R1
is an alkyl group having 3 to 30 carbon atoms, such as 2-methylpropyl, 2-methylbutyl, 2,2-dimethylpropyl,
2-methylpentyl, 2,2-dimethylbutyl, 2,3
-dimethylbutyl, 2-methylhexyl, 3-ethylpentyl, 2,2.4-)limethylpentyl, propyl,
Butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, heneicosyl, tocosyl, tetradecyl, bentacyl, hexanoyl, heptadecyl, ophtacosyl, nonacosyl,
Indicates triacontyl group, etc. Among these, carbon number 1
Those with numbers 6 to 26 are particularly preferred because they are relatively easy to synthesize and also have excellent antigenicity.

Furthermore, the lower alkanoyl group for R2 has 1 to 1 carbon atoms.
6 represents a straight chain or branched chain alkanoyl group, such as formyl, acetyl, propionyl, butyryl, pentanoyl, hexanoyl group and the like.

The Le"m conductor of the present invention can be prepared, for example, by the following reaction process formula (1):
It can be synthesized by the method shown below.

In addition, the symbols used in the following reaction process formula have the following meanings.

The LeY derivative of the present invention is produced by combining a large glucosamine synthesizing element (I [ (I) is produced.

The manufacturing method for each of these synthetic elements and the reaction steps described above will be explained below.

l) Synthesis method of glucosamine synthesis element (II[) According to the following reaction scheme (2), glucosamine synthesis element (I[[
) is manufactured.

Hereinafter, margin α.That is, each reaction shown in reaction step (2) can be carried out by a commonly used method, for example, by the following method.

Step (i) is to neutralize D-glucosamine hydrochloride to produce D-
This is the process of obtaining glucosamine. As a neutralizing agent, an organic base such as triethylamine or diethylamine is used.

Step (if) is a step of obtaining an acetylated form of D-glucosamine by reacting D-glucosamine obtained in step (i) with an acetylating agent. The acetylating agent may be any one that is commonly used for acetylation, and for example, acetic anhydride is preferred. The reaction is preferably carried out in the presence of a neutralizing agent such as pyridine.

Step (iii) is a step of ether bonding a desired alkyl group to the 1-position of the acetylated product obtained in step (ii). The reaction is carried out by dissolving a desiccant and a Lewis acid in a suitable solvent, mixing the acetylated product and an alcohol having a desired alkyl group therein, and reacting the mixture. Examples of the solvent used here include commonly used organic solvents such as methylene chloride and chloroform, and as the desiccant, neutral desiccants such as calcium sulfate and molecular sieve are preferred. Also,
Examples of Lewis acids include iron(III) chloride, )! Examples include J fluoromethanesulfonate, 3-fluoroboron etherate, tin chloride (rV), and examples of the alcohol include primary saturated alcohols containing a desired alkyl group. The reaction may be carried out at room temperature overnight.

Step (iv) is a step of benzylidene-forming the D-acetylglucosamine-1-alkylated product obtained in step (iii). First, the alkylated product is dissolved in a suitable solvent, and a base such as sodium methoxide or sodium hydroxide is added thereto for reaction. Next, the base is neutralized by applying it to a cation exchange resin or using a commonly used acid, concentrated under reduced pressure, and then converted to benzylidene. As a method for benzylidene formation, for example, ■ Adding benzaldehyde and a catalyst such as zinc chloride, ■
Examples include adding benzaldehyde acetal, tosylic acid, and camphorsulfonic acid.

Step (V) is a step of acylating the hydroxyl group at the 3-position of the benzylidene obtained in step (iv).

The reaction is carried out by reacting the benzylidene compound with an acylating agent such as acetic anhydride.

Finally, step (vi) is a step of ring-opening the acylated benzylidene obtained in step (V). The reaction is
For example, the benzylidene described above is dissolved in a suitable solvent and added to sodium cyanoborohydride, lc1. -LiAIH,
It is carried out by reacting with a reducing agent such as. When sodium cyanoborohydride is used, it is preferable to dropwise add a saturated ether solution of HCl. After the reaction, the glucosamine synthesis element (II
I) can be obtained.

2) Synthesis method of galactose synthesis element (rV) A galactose synthesis element (IV) is produced according to the following reaction process formula (3).

Each reaction shown in the margin below, that is, reaction process formula (3), can be carried out by a commonly used method, for example, by the following method.

Step (i) is a step in which only the 3-hydroxyl group of D-galactose is benzylated. First, methyl 3-0-benzyl-β-D-galactopyranoside can be obtained by methylating the 1-position hydroxyl group of commercially available D-galactose by a conventional method.

Step (ii) is the methyl 3-〇- obtained in step (i)
This is a process in which the benzylidene form of benzy-β-D-galactopyranoside is converted to a base, for example, by reacting a benzylidene forming agent such as benzaldehyde in the presence of a catalyst such as zinc chloride to form methyl 3-O-benzyl-4, 6-〇-
Benzylidene-β-D-galactopyranoside can be obtained.

Step (iii) is a step of acylating the hydroxyl group at the 2-position of the benzylidene compound obtained in step (ii).

The reaction is carried out by dissolving the benzylidene compound in a solvent such as pyridine, and then reacting it with an acylating agent such as a benzoyl halide such as benzoyl bromide and benzoyl chloride.

Step (iv) is carried out by subjecting the benzylidene compound acylated in step (iii) to acid hydrolysis using an appropriate acid such as hydrochloric acid or acetic acid.

Step (V) is a step of benzylating the 4- and 6-position hydroxyl groups of methyl 2-acyl-3-0-benzyl-β-D-galactopyranoside obtained in step (iv). The benzylation reaction may be carried out, for example, in the presence of a suitable base by adding a benzyl halide activator such as tetrabutylammonium iodide and a benzylation agent such as a benzyl halide such as benzyl bromide or benzyl chloride. This is done by

Step (vi) is a step of substituting the methoxy group at the 1-position of the methyl 2-acyl-3,4,6-)cou-0-benzyl-β-D-galactopyranoside obtained in step (V) with a hydroxyl group. It is. The reaction is carried out by treating the methylated product with hydrochloric acid, acetic acid, etc. under acidic conditions.

Finally, step (vii) is the step (vii) of 2 obtained in step (vi).
-○-benzoyl-3.4.6-) Lee○-benzyl- This is a step of substituting the 1-position hydroxyl group of D-galactose with a para-nitrobenzoyl group to synthesize a galactose synthesis element (IV). In this reaction, paranitrobenzoyl halides such as valanitrobenzoyl bromide and paranitrobenzoyl chloride are used as the noranitrobenzoylating agent.

3) Synthesis method of fucose synthesis element (V) According to the following reaction scheme (4), the fucose synthesis element (V
) is manufactured.

Each reaction shown in the margin below, that is, reaction process formula (4), can be carried out by a commonly used method, for example, by the following method.

Step (i) is 2.3 of the 1-0-methyl-L-7 course.
and a step of benzylating the hydroxyl group at the 4-position. The reaction is carried out in the presence of a base using a benzylating agent such as a benzyl halide such as benzyl chloride or benzyl bromide. Note that 1-0-methyl-L-fucose can be obtained, for example, by reacting L-7 course with methanol in the presence of an ion exchange resin.

Step (ii) is a step in which the methoxy group at the 1-position of the benzylated product obtained in step (i) is returned to a hydroxyl group.

The reaction is carried out by treating the benzylated product with hydrochloric acid, acetic acid, etc. under acidic conditions.

Finally, step (iji) is the 2, 3 obtained in (ii)
．． 4-) Di-0-benzyl-6-zooxy-α-L-
This is a step of substituting the hydroxyl group at the 1-position of galactose with a varanitrobenzoyl group to obtain an L-fucose synthesis element (V). The reaction is carried out using the reaction process (v) of the galactose synthesis element described above.
This is done in the same way as ii).

4) Synthesis of LeY derivative The synthetic element synthesized in steps 1) to 3) above is subjected to reaction scheme (1).
According to the method, the Le' derivative of the present invention is produced. That is, each reaction shown in reaction process formula (1) can be carried out by a commonly used method, for example, by the following method.

First, step (i) is a step of binding the glucosamine synthesizing element (III) and the galactose synthesizing element (rV). For example, galactose synthesis element (IV) is dissolved in a suitable solvent, and a 20 to 40%, preferably 30% or more hydrogen bromide acetic acid solution or a hydrogen bromide saturated methylene chloride solution is added thereto and reacted to produce the synthesis element (IV). IV) is brominated.

Add this to a solution of glucosamine synthesis element (rV), and further add a reactant of sugar bromide, such as silver salts such as silver triflate, silver perchlorate, silver carbonate, mercury salts, etc., for several minutes or more, preferably 2 minutes. It is carried out by reacting for ~10 hours.

Step (ii) is the conjugate (VT) obtained in step (i)
This is a step in which the acyl groups at the 2'- and 3-positions are eliminated. The reaction is carried out by reacting the conjugate (VI) with a strong base such as sodium methoxide, sodium hydroxide, potassium hydroxide and the like. As the solvent, a solvent having active protons, such as a lower alcohol, a hydrous lower alcohol, a mixture of a lower alcohol and an organic solvent, etc. can be used.

Step (iii) is the conjugate obtained in step (ii) (
(2)) and the fucose synthesis element (V). The PNBz part of the fucose synthesis element (V) is
Bromination is carried out in the same manner as in step (i), and a reactant such as sugar bromide is then added in the same manner as in step (i) to obtain a precursor of a LeY derivative (■).

Finally, step (iv) is a step of converting the benzyl group of the precursor (■) obtained in step (iii) into a hydroxyl group.

The Ley derivative of the present invention can be obtained by subjecting the precursor (■) to catalytic reduction using a reduction catalyst such as palladium or by catalytic hydrogen transfer reduction.

The Ley derivative of the present invention obtained as described above can be used without particularly requiring purification, but it can also be purified, for example, by gel filtration, if necessary.

[Action and effect]

The LeY derivative of the present invention is chemically homogeneous, can be efficiently synthesized in large quantities, and has antigenicity equivalent to natural Le'.

〔Example〕

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 Propyl 2-acetamido-3-〇-(α-L-fucopyranosyl)-4-〇-[2-〇-(
α-L-fucopyranosyl)-βD-galactopyranosyl]-2-deoxy-β-D-glucopyranoside (R1 propyl, R2 = acetyl in the hole (1)) was synthesized.

(1) 2-amino-2-deoxy-D-glucose methanol 100mj! Add diethylamine 9 + nIl to the solution, stir at room temperature, and add 10 g of D-glucosamine hydrochloride.
was added little by little. After continued stirring overnight at room temperature, the resulting precipitate was collected by filtration, washed with cold ethanol, and dried. 7.89 g (95%) of white powder was obtained.

(2) 2-acetamido-1,3,4,6-chitler○
-acetyl-2-deoxy-β-D-glucobylanose acetic anhydride 38+d and pyridine 62ff+j! Mix, 0
It was cooled to <0>C and 6 g of 2-amino-2-deoxy-D-glucose was added. After stirring at room temperature for 3 days, the reaction mixture was cooled with ice, and the resulting precipitate was collected by filtration and washed with cold ethanol. This was dried to obtain 10.9 g (90%) of white powder.

(3) Allyl 2-acetamido-3,4,6-) Lee〇-Dingcetyl-2-deoxy-β-D-glucopyranoside Add 4 g of calcium sulfate and 3 g of ferric chloride to 40 ml of methylene chloride, and stir at room temperature for 10 minutes. did. Then 2
-acetamido-1,3,4,6-chitler〇-acetyl-2-deoxy-β-D-glucobylanose 3.89
g and 5 ml of allyl alcohol were added and stirred overnight. The reaction mixture was poured into an ice-cooled saturated aqueous sodium hydrogen carbonate solution and stirred until no bubbles were generated. This was extracted with chloroform, washed with water, and dried over anhydrous magnesium sulfate. The solids were then filtered off, the filtrate was concentrated under reduced pressure, and the resulting silica was separated and purified by silica gel column chromatography using benzene-acetone as an eluent. 3.40 g (91%) of white powder was obtained.

'H-NMR spectrum (ppm) δ AM-400CDCL/TMS 1.94-2.07 (s*4, 12H, AC main 4) 3.
69 (ddd, IH, H-5, J,, s”9.8
2. Js, 6a=2.52. J5. ah=4.
84Hz) 3, 87 (dt, Ill, H2, Jl+ 2=8
．． 50. J2.3=10.55. J2. i+l1
=8,59) 4,05-4.11 (m, LH,0-[:R2-C
H=C)1. a) 4, 13 (dd, l) I, H-
6a, J, , gb=12.24) 4, 25 (d
d, IH, H-6b) 4.30-4.35 (m,
ill, 0-CH,-CH=CH2)4.71 (d
, LH,H-1) 5,06 (t, ill, H-4,J,, 4=9
．． 44) 5, 175.20 (m, IH, CL-CH
=CH2-a)5,23-5.28 (m, IH,C
H2-CH=CH2b)5.29 (dd, ill,
H-3>5, 60 (d, IH, NH) 5, 81-5.90 (m, LH, (:L-Ctl=
CL) (4) Allyl 2-acetamide-4,6-〇-benzylidene-2-deoxy-β-D-glucopyranoside methanol 40mj2 to allyl-2-acetamide-3
,4,6-)Le○-acetyl-2-deoxy-β-D
- 1.55 g of glucopyranoside was dissolved, 1.08 g of sodium methoxide powder was added under water cooling, and the mixture was reacted at room temperature for 4 days. Cation exchange resin Amberly) IR
-120B was added to neutralize the mixture, and the mixture was compressed under reduced pressure to obtain a syrup. Add to this 2 g of zinc chloride and 10 m of benzaldehyde.
11 was added and stirred overnight at room temperature. 5 each of water and hexane
0ml was added and stirred at room temperature, and the resulting precipitate was collected by filtration and washed with hexane until the benzaldehyde odor disappeared. After drying, 1.26 g (90%) of white powder was obtained.

'H-NMR spectrum (ppm) δ AM-400CDC1,/TMS 2.05 (s, 3H, Ac) 3.45-3.53 (m, 2H,H-2,8-6a
) 3, 49 (dd, H-6a, Js, 5a=9
．． 35. Jsa, sb"9.94Hz) 3, 57
(t, IH, H-3, J2. , =9.11. J,
, ,=9.63)3.79 (t, LH,H-4,
J4. s=9.72) 4, 08-4.13 (m,
18.0-CFIz-CH=CH2a)4.19 (t
, IH,H-5,J, , , =9.86) 4, 32
-4.38 (m, 2H, H-6b, Cl-CH2
-f:H=C)I2b)4.34 (dd, H-6b
) 4,78(d, 1B, H1,,L, 2”8.26
)5, 23-5.33 (m, 2N, CHa-CH
=CH2)5,55(s, 1)1. Benzylidene-H
) 5.72 (bs, LH, 0H) 5, 86-5.95 (m, IN, C) 12-C)
l=['H2)7.34-7.52 (m, 5H, A07 Teitku H) (5) Allyl 2-acetamido-4,6-〇-benzylidene-3-〇-chloroacetyl-2-deoxyβ- D-Glucopyranoside Allyl 2-acetamido-4,6-〇-benzylidene-2-deoxy-β-D-glucopyranoside 3.49g and pyridine 3.5+nj! methylene chloride 300+++
j! A solution of 3 ml of chlorocetyl chloride in methylene chloride (50 ITIIl) was added dropwise under ice-salt cooling. The reaction mixture was returned to room temperature and stirred for an additional 2 days. The mixture was neutralized by adding IJum, dried with magnesium sulfate, and concentrated under reduced pressure to obtain crude crystals.

Recrystallize from ethanol to obtain white crystals. ? Og(
64%> obtained.

'H-NMR spectrum (ppm) δ AM-400CDCN3/TMS 1, 97 (s, 3) 1. Ac) 3, 53 (dt, LH, H-5, J4. s=9.
86. Js, s□=9.59. JS+ab=4
, 88tlz) 3, 74 (t, IH, H-6a, Jsa, 5b=
to, 02) 3.81 (t, 1)1. H-4,
J3.4=10.09) 4, 02-4.09 (m,
4H,H-2,0-CHz-CH=C)12-.

C1-CH2-CD) 4,30-4.35 (m, IH,0-C11i-C
H=CH2b) 4, 36 (dd, LH, If-6b
)4,67 (d, LH,H-1,J,1=8.61
)5, 19-5.30 (m, 2H, CH2-CH=
CH2)5,38 (t, ill, H-3)5,5
1 (s, LH, benzylidene-H)5, 57 (d
, 1N, NH) 5,81-5.89 (m, 1N, CH, -CH=
CH2) 7, 27-7, 44 (m, 5H, A07 Teitku H) (6) Allyl 2-acetamido-6-
〇-Benzyl-3-〇-chloroacetyl-2-deoxy-β-D-glucopyranoside freshly distilled tetrahydrofuran (T) IF) 70
0ml, allyl 2-acedoamide-4,6-0-benzylidene-3-〇-chloroacetyl-2-deoxy-β
-D~ 3.19 g of glucopyranoside and 4 g of molecular sieve MS3-A were added and stirred at room temperature for 10 minutes.

After adding 5 g of sodium cyanoborohydride, a saturated ethereal solution of hydrogen chloride was added dropwise until the generation of bubbles stopped. After further stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure, neutralized by adding sodium bicarbonate, extracted with chloroform, dried using magnesium sulfate, and concentrated under reduced pressure.

The residue was separated and purified by silica gel column chromatography using chloroform-methanol as an eluent to obtain 2.31 g (73%) of white crystals.

'H-NMR spectrum (ppm) δ to M-400CD (j!, /TMS 1,94 (s, 3H, Ac) 3,57 (dt, 1) 1. H-5, J4. s=
9.51. Js, 6=4.75Hz) 3, 75 (
t, IH, H-4, J3.4=9.96) 3, 78
(d, 2H, H-6) 3.93 (dt, IH,) I-2, J 1.2=8
．． 61. Jl, 3=10.40. Jl, NH-
4,82) 4,04-4.10 (m, LH,0-Ctl, -C
H=CH2a)4,12(s, 2H,Cj'-CL-
CD) 4,28-4.33 (m, LH,0-CH2
-CH=CH2b)4,54-4.62 (m, 2H
, benzyl-○) 4,61 (d, H-1) 5,15-5.27 (m, 3N, H-3, CI2
-CH=CH2)5,21 (dd, H-3) 5,80-5.90 (m, IH,CH--Ctl=
CL)5.98 (m, 2N, NH,DH)7,2
5-7.36 (m, 5tl, A07TE4”/Kuh
) (7) Methyl β-D-galactopyranoside 2.000 mj of methanol saturated with hydrogen chloride! 180 g of D-galactose was added to the mixture, and the mixture was heated under reflux for 24 hours. After condensing the reaction mixture under reduced pressure with S, the resulting silica was dissolved in hot ethanol, and after cooling, 72.2 g (37%) of white crystals were obtained.

'H-NMR spectrum (ppm) δ JNM FX-200CDCj'3/TMS1, 96
(s, 3tl, Ac) 3, 24-4.70 (n+, 23H, ring-H,
Benzyl-HlO-CH2-CH=CL, C7! -C
L-CO)4,34 (d, H(, J l, 2=8
．． 06Hz) 4, 47 (d, H-1°+Jl・1・
=7.98)4,90-5.22 (m,4H,benzyl-H,H-3,CH2-CH=CH2)5,04
(dd, H-3, J=8.54.9.52) 5, 41
(dd, 1)1. H-2°, Jl-,,-=1
0.14) 5, 65-5.87 (m, IH, CH2
-CH=CH2)5,96 (d, 1B, NH,J
l, NH-4,28) 7,00-'? , 90 (m
, 25B, Ryo07 Teitsuku H) (8) Methyl 3-0
-Benzyl-β-D-galactopyranoside 13.58 g of methyl β-D-galactopyranoside and 19.1 g of dibutyltin oxide were added to 450 ml of benzene.
? g was added thereto, and the mixture was heated under reflux for 4 days while removing the resulting water azeotropically. After cooling the reaction mixture, add 28.41 g of tetrabutylammonium iodide to 9.1 g of benzyl bromide.
3mf was added and the mixture was further heated under reflux overnight. The reaction solution is about 3
The resulting solution was concentrated under reduced pressure to 1/2 volume, and the resulting crystals were collected by filtration and washed with a small amount of cold ether to obtain 16.92 g (85%) of white crystals.

'H-NMR spectrum JLz (ppm) δJNM F
X-200CDCj' 3/TMS1, 98 (s,
3H, AC) 3, 28-4.90 (111,288, ring-■,
Benzyl H9O-C)'Iz-CH"C)12.C1
-CHz-CO, 08 lines 2) 3, 34 (dd, H-
3°, J2°, , -=9.89. J3°, ,・=
2.81) 12) 4, 25 (d, H-1, J,, 2=
7.81) 4.47(d, H-1', Jl, 1=8.3
0) 5, 10-5.32 (m, 21(, CH2-C
H=CH2)5,71-5.98 (m, 2H,NH
, CH2-CH=CH-)5,76 (d, NH,J
L N11=7.56) 7, 18-7.43 (m,
20H, A07 Teitsuku H) (9) Methyl 3-○-benzyru 4.6-0-benzylidene-β-D-galactopyranoside 40 g of methyl 3-○-benzyru β-D-galactopyranoside and zinc chloride 300 benzaldehyde per 100g
ml was added and stirred at room temperature for 2 days. 250 mf each of water and hexane were added and stirred, and the resulting crystals were collected by filtration. 4
2.26g (81%)'H-NMR spectrum (ppm
)δ JNM FX-200CDC1,/TMS1, 10
(d, F-6, J=6.10Hz)l, 2? (d
, F-6, J=6.10) 1.56 (s, Ac) 2, 88-5.45 (m, Ring-H, Benzyl-〇.

0-CH,-CH=CH2) 4,87 (F-1,J=3.91) 5,61 (d, NH,J=6.35)5,67 (
d, F-1, J=3.90)5, 72-5.97 (
m, CH2-CH=CH2)6,70-7゜24(T
Romantic-〇)ilG Methyl 2-○-benzoyl-3-〇-benzyl-4,6-〇-benzylidene-β
-D-galactopyranoside pyridine 200mj2, methyl 3-○-benzyru4
, 6-○-benzylidene-β-D-galactopyranoside (10 g) was dissolved, 10 mf of benzoyl chloride was added dropwise at 0° C., and the mixture was stirred overnight at room temperature.

The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous solution of hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography using a benzene-7-ton system as an eluent to quantitatively obtain white crystals.

'H-NMR spectrum (ppm) δ JNM FX-2000M5O-d, /CH,C0CH
.

0,86 (t, 0-CHI-CH2-C)1. )1
．． 10-1.35 (m, P-6 pieces 2.0-CH2-CH
2-CH5) 1, 15 (d, F-6, J=7.08
) 1z) 1, 19 (d, F-6, J='/, 08
)2,03 (s, Ac) 3,30-5.35 (ring-H,OH,0-CHz
-CH2-CTo)5, 07 (d, F-1, J=2
．． 20) 5.28 (bs, F-1) αυ Methyl 2-0-benzoyl-3-〇-benzyl β-D-galactopyranoside methyl 2-O-benzoyl-3-0- in 300 ml of 60% acetic acid aqueous solution Benzyl-4,6-〇-benzylidene-β
- Add 11.8g of D-galactopyranoside and add about 80℃
The mixture was allowed to react for 12 hours. The reaction solution was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution to neutralize it, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography using benzene-7ton system as an eluent to obtain 9.62% (84%) of colorless silica.

0 Methyl 2-0-benzoyl-3,4,6-)ly-benzyl-β-D-galactopyranoside methyl 2-0
-Benzyl-3-〇-benzyl-β-D-galactopyranoside (8.02 g) was dissolved in 500 ml of dimethylformamide (DMF), and at 0°C 24 g of benzyl bromide was dissolved.
．． 59 Width 11 Tetrabutylammonium iodide 76.
3 mg and 1.98 g of sodium hydride were added.
Allowed time to react. After stopping the reaction by adding acetic acid dropwise, the mixture was concentrated under reduced pressure, and the residue was poured into an ice-cooled saturated aqueous solution of hydrogen carbonate (U) for neutralization, extracted with chloroform, dried over magnesium sulfate, and condensed under reduced pressure. The residue was separated and purified by silica gel column chromatography using benzene-acetone as an eluent to obtain 111.36 g of pale yellow silane (
97%).

C32-0-benzoyl-3,4,6-) ly○-benzyl-D-galactose 80% acetic acid 40ml and methyl 2-○-benzoyl3.
4.6-) Lee O-benzyru β-D-galactopyranoside 3. Dissolve OOg and add 1N hydrochloric acid 20+
nj! was added and reacted at about 100°C for 7 hours. The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography using benzene-acetone as an eluent to obtain 1.77 g (61%) of pale yellow crystals.

α4) 2-0-benzoyl-3,4,6-)ku0
-benzyl-1-0-paranitrobenzoyl-α-ri-monogalactobyranose 2-0-benzoyl-3,4 in 300 ml of methylene chloride
, 6-) Ku0-benzyru-D-galactoseph, 50
g was dissolved, and 12 ml of pyridine was added at 0°C. Here, 50 methylene chloride solution of 3 g of para-nitrobenzoyl chloride
ml was added dropwise and reacted for 12 hours. The reaction solution was poured into an ice-cooled saturated hydrogen carbonate solution (IJ rum aqueous solution), neutralized, extracted with chloroform, dried using magnesium sulfate,
It was concentrated under reduced pressure.

The residue was separated and purified by silica gel column chromatography using benzene-acetone as an eluent to obtain 8.79 g (92%) of pale yellow crystals.

■ Add 8 g of methyl 6-thioxidi α-L-galactopyranoside L-fucose to 80 ml of methanol and wash with methanol to add 8 g of Amberlite IR-1208 resin.
was added and heated under reflux for 18 hours. The cold resin was removed and the mixture was concentrated under reduced pressure, and ethanol was added to the resulting silica to crystallize it. 5.47g (63%) Methyl 2.3.4-
) Li○-benzyru-6-zooxy-α-L-galactopyranoside To 60 ml of toluene were added 5 g of methyl 6-thioxidi α-L-galactopyranoside, 40 ml of benzyl chloride, and 15 g of powdered potassium hydroxide, and the mixture was heated under reflux overnight. did. Cold water was added and the organic layer was separated, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a sillage. This was purified by silica gel column croftography using benzene as an eluent, yielding 9.78 g (78%) of pale yellow silica.
I got it.

α'Q 2.3.4-) Coo-0-benzyl-6-zooxy-α-L-galactose 80% acetic acid 160+nj! Mix 50 mj7 of 1N hydrochloric acid and add 8 g of methyl 2.3.4-
The reaction was carried out at 00°C for 2 hours. After cooling, chloroform was added and the mixture was washed with ice-cooled saturated aqueous sodium hydrogen carbonate solution and water. It was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by column chromatography using benzene-ethyl acetate as an eluent to obtain 5.72 (74%) of white crystals.

(2) 2.3.4-) 0-benzy-6-zooxy-l-〇-paranitrobenzoyl α and β-L-
Galactopyranose 2,3,4-tri〇-benzyru-6-zooxy-α-
11.0 g of L-galactose and 300 m of methylene chloride
ji! 50 mj of a methylene chloride solution of 15 ml of pyridine and 6 g of balanitrobenzoyl chloride at 0°C. was added and allowed to react overnight. The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography using benzene as an eluent, and pale yellow crystals with a purity of 7.04% were obtained.
g (β52%) and 4.48 g (α3
3%) obtained.

(To) Allyl 2-acetamido-4-〇-(2-〇-benzoyl-3.4.6-) Lee○-benzyl-β-D
-galactopyranosyl)-6-0-benzyl-3-0-
2-0-benzoyl-3,4,6-)li obtained with chloroacetyl-2-deoxy-β-D-glucopyranoside αO
-Benzyl-1-0-paranitrobenzoyl-α-D-
500 mg of galactopyranose and 15 ml of methylene chloride
Molecular sieve MS3A500cm was added to the mixture and stirred for 10 minutes at room temperature. Add 1 ml of 30% hydrogen bromide and acetic acid solution at room temperature, stir for 30 minutes, neutralize the reaction solution by pouring it into ice-cooled saturated aqueous sodium bicarbonate solution, extract with chloroform, dry with magnesium sulfate, and reduce pressure. Concentrated. This residue and allyl 2-acetamido-6-〇-benzyl-3-0-40 loacetyl- obtained in (6)
Dissolve 304 mg of 2-deoxy-β-D-glucopyranoside in 10 ml of methylene chloride and add molecular sieve A.
W-300500 was added and stirred at room temperature for 10 minutes. 91.4 µm of silver triflate was added thereto, and the mixture was allowed to react at room temperature for 12 hours.

The reaction solution was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution for neutralization, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography using benzene-ethyl acetate as the eluent.
104 mg (15%) of white powder was obtained.

(1) Allyl 2-acetamido-4-0-(3,4,
6-tri〇-benzy-β-D-galactopyranosyl)-6-〇-benzy-2-deoxy-β-D-glucopyranoside methanol 10mj! , allyl 2-acetamido-4-〇-(2-O-
benzoyl-3,4,6-)lyO-benzyl-β-D
-galactopyranosyl)-6-〇-benzyru3-〇-
Add 80 mg of chloroacetyl-2-deoxy-β-D-glucopyranoside, and add 10 mg of sodium methoxide.
(2) was added and stirred at room temperature for 18 hours. After terminating the reaction by adding 2 ml of acetic acid dropwise, the mixture was concentrated, the residue was neutralized by pouring it into an ice-cooled saturated aqueous sodium bicarbonate solution, extracted with chloroform, dried over magnesium sulfate, and condensed under reduced pressure.

This was purified by column chromatography using benzene-ethyl acetate as the eluent, yielding 61 mg (94%) of white powder.
)Obtained.

(21> Allyl 2-acetamido-6-0-benzyl-
3-〇-(2,3,4-tri〇-benzyru α-L-
Fucopyranosyl〉-4-〇-[3,4,6-)Le○-
Benzyl-2-0-(2,3,4-)-benzy-α-L-fucopyranosyl)-β-D-galactopyranosyl]-2-deoxy-β-D-glucopyranoside 2,3.4-) Lee○-benzyru6-zooxy1
Dissolve 200 mg of -0-paranitrobenzoyl-α or -β-L-galactopyranose in 4 ml of methylene chloride, add 500 mg of molecular sieve MS3A, and
The mixture was stirred at ℃ for 10 minutes. 2 ml of hydrogen bromide saturated methylene chloride solution was added thereto, the temperature was returned to room temperature, and the reaction was allowed to proceed for an additional 10 minutes. The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. This residue and allyl 2-acetamido-4-〇-(3,4,6-)ly○
-Benzyl-β-D-galactopyranosyl)-6-〇-
Benzyl-2-deoxy-β-D-glucopyranoside 6
Dissolve 1■ in a 1:1 mixture of benzene and nitromethane, add Molex Collar Sieve MS4A500■, and stir at room temperature for 10
The mixture was stirred for a minute. 100 μm of mercury cyanide (It) was added thereto, and the mixture was allowed to react for 600 hours. The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure.

This residue was purified by column chromatography using benzene-ethyl acetate as the eluent to obtain 52 mg of white powder (
41%).

(22) Propyl 2-acetamido-3-〇-(α-L
-fucopyranosyl)-4-〇-[2-〇-(α-L-fucopyranosyl)-β-D-galactopyranosyl]-2-
Deoxy-β-D-glucopyranoside allyl 2-acetamido-6-〇-benzyl-3-0-
(2,3,4-)Li○-benzyru α-L-fucopyranosyl)-4-〇-[3,4,6-)Li0-benzyru α−
L-fucopyranosyl)-β-D-galactopyranosyl]
-2-deoxy-β-D-glucopyranoside (52 mg) was dissolved in methanol (10 mA) and 10% palladium on carbon 5 was added.
00 mg and 1 ml of formic acid were added and reacted at room temperature for 1 hour. The reaction mixture was filtered using a filter aid and concentrated under reduced pressure to obtain 20 μg (90%) of a slightly yellow glass.

Example 2 Decyl 2-acetamide-3-〇-
(α-L-fucopyranosyl)-4-0-[2-〇-(α
-L-fucopyranosyl)-β-D-galactopyranosyl]-2-deoxy-β-D-glucopyranoside (-R'=C2°H21% R2=acetyl) in the hole (I).

(1) Decyl 2-acetamido-3,4,6-)-O-acetyl-2-deoxy-β-D-glucopyranoside methylene chloride 300mj! In, molecular sieve AW
-3003g, decanol 4.29mj! and Example 1
2-acetamide-1,3,4゜6- obtained by
Add 10.5 g of Chitler○-acetyl-2-deoxy-β-ri-glucobylanose and stir at room temperature under nitrogen atmosphere.
Stirred for 0 minutes. then trimethylsilyl trifler)
4.35mj! was added and stirred overnight. The reaction mixture was poured into an ice-cooled saturated aqueous sodium hydrogen carbonate solution and stirred until no bubbles were generated. This was extracted with chloroform, washed with water, and dried over anhydrous magnesium sulfate. The solid was then filtered off, the filtrate was concentrated under reduced pressure, and the resulting solid was separated and purified by silica gel column chromatography using benzene-acetone as an eluent.

11.0 g (83%) of white powder was obtained.

'H-NMR spectrum (ppm) δ JNM G5X-500CDCZ3/TMSO, 88 (
t, 3H, R-CH3) 1.15-1.37 (m, 14H, CH, book 7) 1,
50-1.63 (m, 2H,0-CH2-CH2-
R) 1, 96-2.10 (s*4.12H, AC) 3
．． 47 (dt, IH, low CL-Ra) 3.71 (d
dd, l)l, H-5, Jl, s=9.85.
Js, 1-=2.44°Js, gb"4.81Hz
) 3,80-3.92 (m, 2H,H-2,0-CH
, -Rb) 4, 13 (dd, LH, H-6a, J
a,, 5b42.37) 4.27 (dd, 18.
H-6b) 4, 70 (d, LH, H-1, J+,
2=8.25)5,06 (t, 18.H-4,J
l, 4=9.50)5.32 (t, 1)1. H
-3, Jl, s=9.37)5,64(b, LH,
NH) (2) Decyl 2-acetamide-4,6-〇-benzylidene-2-deoxy-β-D-glucopyranoside methanol 200ml 17 to decyl-2-acetamide-
3,4,6-)Le○-acetyl-2-deoxy-β-
Dissolve 10.0 g of D-glucopyranoside, add 4.4 g of sodium methoxide powder under water cooling, and dissolve at room temperature.
I reacted for a day. Acidic ion exchange resin Amberly) IR
-120B was added to neutralize the mixture, and the mixture was concentrated under reduced pressure to obtain Shirabu. Add to this 20g of zinc chloride and 10g of benzaldehyde.
0mI! was added and stirred at room temperature for 3 days. 250 mj7 each of water and hexane were added and stirred at room temperature, and the resulting precipitate was collected by filtration and washed with hexane until the benzaldehyde odor disappeared. After drying, 6.35 g (69%) of white powder was obtained.

'H-NMR spectrum (ppm) δ JNM G5X-5000M5O-da/TMSO, 8
6(t, 3)1. R-CH3) 1.17-1.34
(m, 141 (, C82 7) 1, 34-1.50 (
m, 2H,0-CH2-CH,-R)1,80 (s
, 3H, Ac) 3,24-3.53 (m, 4H,H-2,H-4,
H-5,0-C)I*-Ra)3,41 (t, h-
4, Js, 4=9.16. J4. s=8.94H
z) 3°49 (Q, H-2, J+, 2=8.8
2. Jl, 3=9.10. Jl, wu=9.0
5) 3,60 (dt, 1H,)l-3,Jl,. □
=5.61) 3, 64J, 77 (m, 2H,H-
6a, 0-CHa-Rb)3,72 (t, H-6
a, Js,, ab=lo, 20) 4, 19 (d
d, IH,H-6b) 4, 46 (d, IH,H-
1) 5, 24 (d, 18.0H) 5, 59 (s, LH, benzylidene-〇) 7, 32
-7.52 (m, 5H, γ Romantic H>7,
79 (d, LH, NH) (3) Decyl 2-acetamido-3-0-acetyl-4
,6-0-benzylidene-2-deoxy-β-D-glucopyranosidedecyl 2-acetamido-4,6-〇-benzylidene-2-deoxy-β-D-glucopyranoside 6.35 g
was dissolved in 60mf of pyridine, and 40+n of acetic anhydride was added under water cooling.
j2 was added and stirred at room temperature for 1 day. After neutralization by adding sodium hydrogen oxide while cooling with water, the mixture was extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure to obtain crude crystals. Recrystallized from ethanol to obtain 6.94 g of white crystals (quantitative)
Obtained.

'H-NMR spectrum (ppm) δ JNM G5X-500CD (j!, /TMSO, 87
(t, 3H, R-C)13) 1.12 1.38 (
m, 14N, CLOT) 1,42-1.60 (m,
2H,0-CH--CH2R) 1.96(s, 3tl
, Ac) 2,06 (s, 3)1. Ac) 3,35 (dt, LH,0-CHa-Ra)3.4
3-3,86 (m, 4H, H-4, H-5,)I-6
a, low C11, -Rb) 4.08 (Q, LH, H
-2,,L,2=8.83. Jl, 3=9.5
2. Jl, M11=9, 36Hz) 4.37 (dd, IH, J-6b, J=4.77
, 10.14) 4, 46 (d, ill, H-1)
5, 24 (t, IH, H-3, Jl, 4=9.7
6) 5, 49 (s, IH, benzylidene-H) 6,
09 (cl, 1) 1. N)I)? , 25-7.4
7 (m, 5B, A07Te4-/Kuh) (4) Decyl 2-acetamido-3-〇-acetyl-6-○-benzy-2-deoxy-β-D-glucopyranoside freshly distilled tetrahydrofuran (THF) 50
mn1. :, 7” syl 2-acetamido-3-〇-acetyl-4.6-〇-benzylidene-2-deoxy-βD
- 3.00 g of glucopyranoside and 1 g of molecular sieve MS3-A were added and stirred at room temperature for 10 minutes. 3g
After adding sodium cyanoborohydride, a saturated ethereal solution of hydrogen chloride was added dropwise until the generation of bubbles stopped. After further stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure, neutralized with addition of hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure.

The residue was separated and purified by silica gel column chromatography using chloroform-methanol as an eluent to obtain 2.83 g (94%) of white crystals.

'H-NMR spectrum (ppm) δ JNM G5X-500CDCJ! 3/TMS0,88
(t, 3H,R-[:H,)1.10(,35(m
, 14H, C82 7) 1, 45-1.62 (m,
2)1.0-C)1. -CH, -R)1,94 (s,
3H, AC) 2,10 (s, 3H, Ac) 3.20-3.95 (m, 8H, Ring I1.
Otl, low CH, -R) 4.50 (d, LH, H
−1, J, , , = 8.30Hz) 4.59 (dd
, 2H, benzyl-H)5,07 (dd, IH,
H-3, J = 8.92.10.63) 5, 77 (d,
LH, NH, Jl, *u=9.28) 7, 24-7
．． 40 (m, 5H, AO?T'/ChuH) (5)
Decyl 2-acetamido-3-0-acetyl-4-〇-
(2-O-benzoyl-3,4,6-tri〇-benzyl-β-D-galactopyranosyl)-6-〇-benzyl-2-deoxy-β-D-glucopyranoside 2- obtained in α0 of Example 1 ○-benzoyl 3.4゜6
-) IJ-○-benzyru-1-○-paranitrobenzoyl-α-D-galactopyranose 500■ was dissolved in methylene chloride 15+++Il, and molecular sieve MS3
500 ml of A was added and stirred at room temperature for 10 minutes. To this was added 1 ml of 30% hydrogen bromide acetic acid solution at room temperature, stirred for 30 minutes, neutralized by pouring the reaction solution into ice-cooled saturated aqueous sodium bicarbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. did. This residue and decyl 2-acetamido-3-〇-acetyl-6-0-benzyl-2-deoxy-β-D-glucopyranoside 493m
g to 30mj of methylene chloride! 3002 g of molecular sieve ΔW-3 was added thereto, and the mixture was stirred at room temperature for 10 minutes.

Add 257 mg of silver triflate to this and let it cool for 40 minutes at room temperature.
Allowed time to react. The reaction solution was cooled with ice-cooled saturated hydrogen carbonate)
Pour into IJum aqueous solution to neutralize, extract with chloroform,
It was dried using magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography using benzene-ethyl acetate as an eluent to obtain 392 ml (38%) of a white powder.

'H-NMR spectrum (pp+n) δJNM G5X
-500CDC1,/TMS0,87 (t, 3H,
R-CHa)1,12-1.30 (m, 14H,C
H, *7) 1, 45 (, 52 (m, 2H, 0-CL-
CL-R) 1,90 (s, 3H, Ac) 1,94 (s, 3H, Ac) 3, 2Hdt, 2H,0-C)I2-Ra) 3.38
(d Ren, 1N, H-5, J-, s=7.79.J6.
-=3.89, 7.79Hz) 3, 46-3.58 (
m, 4H, H-3', H-5', H-6a,
H-6°a) 3, 63-3. TO(m, 3H,H
-6b, H-6°b, 0-C11,-Rb)3,9
0 (t, LH, H-4, J, , , = 7.68) 4
, 01 (d, LH, H-4°j3", 4°=2.7
5) 4, 04 (Q, LH, H-2, Jl, 2=8
．． 71. Jl, 3=8.52. Jl, NH-9
, 16 > 4.17 (d, IH,)I-1) 4,26-4.98 (m, IOH,H-1°, H
-3, benzyl-H)4,51 (d, H-1',
J, ', 2' = 7.94) 4, 94 (t, H
-3) 5.50 (dd, IH, L2', Jl",
s' = 10.09) 5, 63 (d, IH, N) I
) 7, 16-7, 99 <m, 25H, A07 Teitku H) (6) Decyl 2-acetamido-4-0-(3,
Decyl 2-acetamide-3 to 30 ml of methanol
-〇-acetyl-4-〇-(2-0-benzoyl-3,
Add 200 mg of 4,6-)-benzyl-2-deoxy-β-D-glucopyranoside, add 1 g of sodium methoxide, and stir at room temperature for 6 hours. Stirred. Acetic acid 2
mji! was added dropwise to stop the concentration, and the residue was neutralized by pouring it into ice-cooled saturated aqueous sodium bicarbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. This was purified by column chromatography using benzene-ethyl acetate as the eluent, and a white powder was obtained at 1 to 2
mg (quantitative) was obtained.

'H-NMR spectrum (ppm) δ JNM FX-200CDCN3/TMS0, 87-1
．． 64 (m, 19tl, deci, II/-H) 1,98
(s, 3H, Ac) 3,00-4.06 (m, 16H, Ring-H,0
-CH2-R, 01 pieces 2) 4.24 (d, LH, H (
, Jr. 2=7.81Hz) 4, 27-4.91 (
rn, 9t1. H-1', benzyl-1)4,7
7 (d, LL', J +°, 2°=8.31)
5,60 (d, 1)1. NH, J2. *M=7
．． 57) 7,2-7.5 (+n, 20H, a07te4"lkuH) (7) Decyl 2-acetamido-6-〇-benzyl-3-0- (2,3,4-triO- benzyl-α-L-fucopyranosyl)-4-〇-[3,4,
6-) Li○-benzyru2-0- (2,3,4-tri〇-benzyruα-L-fucopyranosyl)-β'-
D-galactopyranosyl]-2-deoxy-β-D-glucopyranoside 2,3.4-) IJ-○~ obtained in Example 1 00
Benzyl-6-zooxy-1-〇-valanitrobenzoyl-α or -β-L-galactopyranose 393mg
was dissolved in 20 ml of methylene chloride, 500 μm of molecular sieve MS3A was added, and the mixture was stirred at 0° C. for 10 minutes. Add 4 mjl of hydrogen bromide saturated methylene chloride solution to it! was added, the temperature was returned to room temperature, and the reaction was continued for an additional 10 minutes. The reaction solution was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution to neutralize it, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure.

This residue and decyl 2-acetamide-4-〇(3,4
, 6-) Lee○-benzyl-β-D-galactopyranosyl)-6-0-benzyl-2-thio-β-D-glucopyranoside (150 mg) in benzene-nitromethane 1:1
Dissolve in the mixture and add molecular sieve MS4A 500
mg was added thereto, and the mixture was stirred at room temperature for 10 minutes. 500 mg of mercury(II) cyanide was added thereto, and the mixture was reacted for 12 hours. The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous solution of hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. This residue was mixed with benzene-
Purification was carried out by column chromatography using ethyl acetate as an eluent, yielding 79.2 cm (27%) of a white powder.

'H-NMR spectrum (ppm) δJNM FX-
200CDC1,/TMS0, 88-1.35 (m,
25)1. Fuc-6 pieces 2. Decyl-H)1,10
(d, Fuc-6, J=6.34)1z)1,56
(s, 3H, AC) 1,62-1.82 (m, 2H,0-CL-C)I
2R) 2.25-5.00 (m, ring-H, 0-C
H2-R, Benji JL/-H) 4, 89 (d, Fu
c-1, J = 3.18) 5.14 (d, IH, GIc
NAc-1, J = 8.05) 5, 59 (d, IH,
NH, J = 6.35) 5, 67 (d, LH, Fuc
-1, J=3.90) 6, 50-7.80 (m, a0
7 Teitsuku H) (8) Decyl 2-acetamido-3-
0-(α-L-fucopyranosyl)-4-〇-[2-〇-
(α-L-fucopyranosyl)-β-D-galactopyranosyl]-2-deoxy-β-D-glucopyranosidedecyl 2-acetamido-6-0-benzyl-3-〇-
(2,3,4-tri〇-benzyl-α-L-fucopyranosyl) -4-0-[3,4,6-tri〇-benzyl-2-〇-(2,3,4-)ly-0-penzyl −α−
L-fucopyranosyl)-β-D-galactopyranosyl]
-2-deoxy-β-D-glucopyranoside 45.4
mg was dissolved in lOmβ methanol, 500 mg of lO% palladium on carbon and 1 rnR of formic acid were added, and the solution was dissolved at room temperature for 12
Allowed time to react. The reaction mixture was filtered using a filter aid and concentrated under reduced pressure to obtain 20.6 mg (95%) of a slightly yellow glass.

'H-NMR spectrum (ppm) δ JNM FX-2000M5O-d6/TMS0, 70
-1.80 (m, Fuc-6 2. Ac, Decyl-H) 3,00-5.50 (m, Ring-H, DH,
0-CH, -R) 4,82 (bs, Fuc-1) 4,95 (bs, Fuc-1) 8,02 (b, NH) Example 3 According to the following method, octadecyl 2-acetamide-3
-0-(α-L-fucopyranosyl)-4-0-C2-0
-(α-L-fucopyranosyl)-β-D-galactopyranosyl]-2-deoxy-β-D-glucopyranoside (
- In the hole (I), R''''CraHsr, R2=acetyl) was synthesized.

(1) Octadecyl 2-acetamido-3,4,6-tri〇-acetyl-2-deoxy-β-D-glucopyranoside methylene chloride 300mj! In, molecular sieve AW
-3003g, octadecanol 7.00g and 2-acetamide obtained in Example 1 (2)-1゜3,4.6-
Add 11.1 g of Chitler○-acetyl-2-deoxy-β-D-glucobylanose and stir at room temperature under nitrogen atmosphere.
Stirred for 0 minutes. Next, 5 ml of trimethylsilyl triflate was added and stirred overnight. The reaction mixture was poured into an ice-cooled saturated aqueous sodium hydrogen carbonate solution and stirred until no bubbles were generated. This was extracted with chloroform, washed with water, and dried over anhydrous magnesium sulfate. The solid was then filtered off, the filtrate was concentrated under reduced pressure, and the resulting solid was separated and purified by silica gel column chromatography using benzene-acetone as an eluent.

15.5 g (quantitative) of white powder was obtained.

'H-NMR spectrum (ppm) δ JNM G5X-500CD (J!3/TMSO, 88
(t, 3H,R-CI(3)1.15(,40(m,
3ON, CL book 15) 1, 50-1.65 (m, 2
H,0-CHz-CHz-R)1.95-2.08 (
+44.12H, Ac) 3, 48 (dt, LH, 0-
CH2-Ra) 3, 73 (ddd, IH, tl-5
, J4. s=9.78. Js, sa”2.36°Js 6-・4,81tlz) 3,80-3.90 (m, 2H,tl-2,0-C
H2-Rh) 4, 13 (dd, LH, H-6a,
Jsa, ab"12.14) 4, 27 (dd, I
H,H-6b) 4,71(d, IH,H-1,J,,
=8.25)5,06 (t, IH,H-4,J,,
, =9.86)5,31 (t, IH,H-3,J
l, = 10.09) 6, 15 (d, 1N, NH,
Jl, +u+=9.03>(2) Octadecyl 2-acetamido-4,6-〇-benzylidene-2-deoxy-β-D-glucopipinoside methylene chloride 100mj! , methanol 200I111
Octadecyl 2-acetamide-3,4,
6-) Li○-acetyl-2-deoxy-β-D-glucopyranoside IL, Og was dissolved, 4 g of sodium methoxide powder was added under water cooling, and the mixture was allowed to react at room temperature for one day. Acidic ion exchange resin Amberly) IR-120B
After neutralization, the mixture was concentrated under reduced pressure to obtain Shirabu. Add to this 50g of zinc chloride and 150mj of benzaldehyde! was added and stirred at room temperature for 3 days. Water and hexa 76250m
1 liter of the mixture was added and stirred at room temperature, and the resulting precipitate was collected by filtration and washed with hexane until the benzaldehyde odor disappeared.

After drying, 9.686 g (94%) of white powder was obtained.

'H-NMR spectrum) Lt (ppm) δJNM F
X-200CDCe3/TMSO188-1,61(m
, 35H, octadecyl-○) 1,92 (s, 3
H, AC) 3.16-4.28 (m, 8H, ring H, 0-
CH2-R,011)4,36 (dd, LH,1(
-6b, J=4.84.10.14Hz) 4, 46
(d, LH, H-1, Jl, 2=8.74) 5, 5
3 (s, LH, benzylidene-H)5, 77 (d
, 1)1. NH, Jl, □=9.21>7, 24-
7.51 (m, 5H, A07 Teitsuku H) (3)
Octadecyl 2-acetamido-3-〇-acetyl-4
．． 6-0-Benzylidene-2-deoxy-β-D-glucopyranoside octadecyl 2-acetamide-4,6-0-benzylidene-2-deoxy-β-D-glucopyranoside 5.6
Dissolve 1g in 60ml of pyridine and add 40ml of acetic anhydride under water cooling.
ml was added and stirred at room temperature for 1 day.

After neutralizing by adding U ram (rehydrated under water cooling with hydrogen chloride), the mixture was extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure to obtain crude crystals. Recrystallization from ethanol yielded 5.55 g (92%) of white crystals.

'H-NMR spectrum (ppm) δ JNM FX-200CDC1,/TMSO, 88-
1,64 (m, 35)1. Octadecyl-H)1,9
4 (9,3H, to C) 2,09 (s, 3H, Ac) 3.51 (dt, LH, low CHz-Ra) 3.57
-3.93 C+++, 4H, H-4, 8-5, 8-6
a, low C) 12-Rb) 4, 08 (Q, 1) 1.
H-2, J+, 2=8.78. J2. s;9.
48゜JL Xl1=9.34Hz) 4, 36 (dd, LH, H-6b, J=4.76
, 10.13Hz) 4, 46 (d, LH, H-1) 5, 23 (t, 18.) I-3, J3. ,=9
．． 79) 5, 48 (s, IH, benzylizo: / -
H) 6, 11 (d, 1) 1. N) Ri7, 26-7, 47 (m, 5H, A07T/KH) (4) Octadecyl 2-acetamide-3-〇-
Acetyl-6-〇-benzyl-2-deoxy-β-D-
Glucopyranoside freshly distilled tetrahydrofuran (THF) 50
mI! , octadecyl 2-acetamido-3-0-acetyl-4,6-○-benzylidene-2-deoxy-β
3.00 g of -D-glucopyranoside and 1 g of monocular sieve MS3-A were added and stirred at room temperature for 10 minutes.

After adding 3 g of sodium cyanoborohydride, a saturated ethereal solution of hydrogen chloride was added dropwise until the generation of bubbles stopped. After further stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure, neutralized by adding sodium bicarbonate, extracted with chloroform, dried using magnesium sulfate, and concentrated under reduced pressure.

The residue was separated and purified by silica gel column chromatography using chloroform-methanol as an eluent to obtain 3.00 g (quantitative) of white crystals.

'H-NMR spectrum (ppm) δ JNM FX-200CDC1,/TMSO, 88-
1,60 (35H, octadecyl-H) 1.94 (s
, 3H, Ac) 2.10 (s, 3H, Ac) 3, 33-3.95 (+t+, 88. Ring-H,
OH,0-CH2-R)4,52 (d, 1)1.
H-1, J12=8.30Hz) 4.59 (dd,
2H, benzyl-H)5,09 (dd, 18.8-
3. J=8.92.10.62)5,96 (d,
ill, NH, J2. *, I"9.03) 7, 25
-7.42 (m, 5H, aromatic-H) (5
) Octadecyl 2-acetamido-3-〇-acetyl-4-0-(2-〇-benzoyl-3.4゜6-tri〇-benzyl-β-D-galactopyranosyl)-6-0-
Benzyl-2-deoxy-β-D-glucopyranoside 2-○-benzoyl obtained from αυ of Example 1 3.4゜6
-Tory〇-benzyru-1-〇-balanitrobenzoyl-α-D-galactopyranose 500mg and methylene chloride 15mj! Molecule Collar Sieve MS3A dissolved in
500 μm was added and stirred at room temperature for 10 minutes. Add 1 ml of 30% hydrogen bromide acetic acid solution to this at room temperature and stir for 30 minutes.
The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. Octadecyl 2-acetamido-3-○-acetyl-6-○-benzyl-2-deoxy-β-D-glucopyranoside (746 mg) and methylene chloride (25 o + j!) Dissolve in molecular sieve AW-
3003 g and 0.177 ml of tetramethylurea were added and stirred at room temperature for 10 minutes. Here is a silver trifler) 317m
g was added thereto, and the mixture was stirred at room temperature for 10 minutes. The concentrated residue of the galactopyranosyl bromide derivative was mixed with 15mj of methylene chloride!
The solution was added dropwise to the above reaction mixture over about 2 hours, and the reaction was further allowed to proceed at room temperature for 90 hours. The reaction solution was poured into a water-cooled saturated aqueous sodium bicarbonate solution to neutralize it, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography using benzene-ethyl acetate as the eluent, and a white powder was obtained with 922%
■(65%) obtained.

'H-NMR spectrum (ppm) δ JNM FX-200CDC1,/TMS0, 8-1.
6 (m, 35H, octadecyl group) 1.89, 1.
94 (S book 2.6H, Ac book 2) 3, 11-5 (, 23
H,! Junk proton, benzyl proton, octadecyl 0-CH2) 4, 18 (d, IH, H-1, J,, 2=7.5
7Hz) 4, 50 (Hl', J+, 1."8.
06Hz) 5, 49 (q, f(-2°, J2-
, 31 = 10.25Hz) 5, 76 (d, LH,
NH, J = 9.28Hz) 7-8 (m, 25N, aromatic proton) (6) Octadecyl 2-acetamido-4-〇-(3,4,6-)Le○-benzyl-β-D-galactopyra nosyl)-6-0-benzyl-2
-deoxy-β-D-glucopyranoside In 30 ml of methanol, add octadecyl 2-acetamido-3-〇-acetyl-4-〇-(2-○-benzoyl-3.4.6-)so-0-benzyl-β-D-galactopyrano sil)-6-〇-benzy-2-deoxy-β-
100 mg of D-glucopyranoside was added thereto, 1 g of sodium methoxide was added thereto, and the mixture was stirred at room temperature for 7 hours.

After terminating the reaction by adding 2 ml of acetic acid dropwise, the mixture was concentrated, and the residue was neutralized by pouring it into ice-cooled saturated aqueous sodium bicarbonate solution, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. This was purified by column chromatography using benzene-ethyl acetate as the eluent, and a white powder with 87%
．． 1 (quantitative) was obtained.

'H-NMR spectrum (ppm) δ JNM FX-200CDC1,/TMS0, 07-1
．． 64 (m, 35H, octadecyl group) 1.96
(s, 3)1. AC) 3, 2-4.1 (m, 16tl, ring proton,
0-C112-R, 08 pieces 2) 4, 25 (d, I
H, H-1, J+, ! =7.57Hz) 4, 3-4
．． 9 (111,9H, benzyl proton, H-1'
)4,73 (H-1', J,9.,,=8.
54Hz) 5, 81 (d, IH, NH, J=7.5
7Hz) 7,2-7.5 (m, 20H, a07te'/kubroton) (7) Octadecyl 2-acetamido-6-〇-benzyru-3-〇-(2,3,4-tri〇-benzyru α -L-fucopyranosyl)-4-〇-(3
,4゜6-tree〇-benzyru2-〇-(2,3,4
-) Li0-benzyruα-L-7cobylanosyl)-β
-D-galactopyranosyl]-2-deoxy-β-D-
Glucopyranoside Example 1 2,3.4-) 0-benzyl-6-zooxy-1-0-paranitrobenzoyl-α
Alternatively, dissolve 820ff1g of mono-β-L-galactopyranose in 50ml of methylene chloride and add molecular sieve M
500 μ of S3A was added and stirred at room temperature for 10 minutes. 24 ml of 30% hydrogen bromide and acetic acid solution was added thereto and reacted for 10 minutes. The reaction solution was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution to neutralize it, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. octadecyl 2
-acetamido-4-〇-(3,4,6-)lyO-benzyl-β-D-galactopyranosyl)-6-0-benzyl-2-deoxy-β-D-glucopyranoside 350
mg was dissolved in 30 ml of a 1:1 mixture of benzene and nitromethane, 1 g of molecular sieve AW-300 was added thereto, and the mixture was stirred at room temperature for 10 minutes. Here, mercury(II) cyanide Ig
A solution of the concentrated residue of the fucosylpromide derivative dissolved in 20 ml of a solution having the same composition was added dropwise over about 2 hours, and the mixture was allowed to react for 15 hours. Pour the reaction solution into ice-cooled saturated aqueous sodium bicarbonate solution to neutralize, extract with chloroform,
It was dried using magnesium sulfate and concentrated under reduced pressure. This residue was purified by column chromatography using benzene-ethyl acetate as the eluent, and 341 mg of slightly yellow glass was obtained.
(53%) obtained.

'H-NMR spectrum (ppm) δ JNM G5X-500CDI, /TMS0, 88
(t, 3H, R-CL, J'6.87Hz) 1.1
0 (d, 3H, Fuc-6, J=5.96) 1.2
-1.34 (II+, 33B, CL book 15.Fuc-6
)1,5(,6(m, 5H,0-CH--CH--R
, [:H*C0NH)2.54 (m, IH,G I
cNAc-2, J = 7.79) 3, 19 (bs, F
uc-4) 3.26 (bd, LH, GlcNAc-5, J=9.
62) 3, 34 (dd, IN, Ga I-5, J
= 5.04.8.71) 3, 45 (dd, 18.0
-CL-Ra, J: 6.8? , 16.49) 3, 5
3 (dd, LH, Ga1-3. J=2.29.9
．． 63) 3, 6-3.65 (m, 21(, G Ic
NAc-6a, Gal-6a) 3, 67 (b s
, 1)1. Fuc-4) 3, 72 (t, LH
, Ga1-6b, J=8.71)3, 75-3.83
(m, 3H, G IcNAc-6b, Fuc-3
,0-CHz-Rh)3,86 (dd, IH,Fu
c-3, J = 1.60.10.31) 3, 92-3.9
8 (m, 3H, GlcNAc-4, Ga1-4.
Pt1-CHza)3, 99-4.1 (m, 38.
Fuc-2, Ga1-2. Fuc-2) 4, 22 (
t, LH, GIcNAc-3, J = 9.4) 4, 28
(dd, Fuc-5, J-6, 41, 12, 83)
4, 34-4.95 (m, 22H, benzyl-8 19. Ga1-1. Fuc-5゜FIJC-1) 4, 52 (d, Ga1-1. J=5.95) 4,
55-4.61 (m, Fuc-5) 4,88 (d
, Fuc-1, J=3.21) 5, 15 (d, 1
)1. GlcNAc-1, J = 8.25) 5.56
(d, 1N, NH, J=6.88)5.67 (d
, IN, Fuc-1, J=4.13) 7.0-7.
4 (m, 50H, A07 Tateku) 1 piece 5Q) (
8) Octadecyl 2-acetamide-3-〇-(α
-L-fucopyranosyl)-4-0-(2-○-(α-L
~Fucopyranosyl)-β-D-galactopyranosyl]-
2-te°oxy-β-D-glucopyranoside octadecyl 2-acetamido-6-〇-benzyl 3
-〇-(2,3,4-tree〇-benzyru α-L-7
Kohira/Sil) -4-0-(3,4,6-)! J
−〇−Benzyru 2−〇−(2,3,4−)−Lee○−
Benzyl-α-L-fucopyranosyl〉-β-D-galactopyranosyl]-2-7"oxy-β-D-4 lucopyranoside (45.4) was dissolved in 10 mJ of methanol, and 10
% palladium on carbon and 1 ml of formic acid were added and reacted at room temperature for 2 hours. The reaction mixture was filtered using a filter aid, and after concentration under reduced pressure, 20.8 mg (9
5%) was obtained.

'H-NMR spectrum (ppm) δ J, NM G5X-5000M5O-d, /TMSO,
86 (t, 3H, R-CH4, J=8.87)1z)
1,05 (d, 3H, Fuc-6, J=6.11)
1,09 (d, 3H, Fuc-6, J=6.41)
1.15 (, 22 (m, 30H, CL book 15) 1, 41
．． 46 (m, 2H,0-CL-Ct12-R)1,
78 (s, 3H, CH, C0)3, 1-3.8 (
a+, Ring-H,0-[')12-R)4.01 (
dd, IH, Fuc-5, J=6.41.12.84
)4, 33 (d, LH, Ga1-1. J=6.8
8) 4, 71 (dd, 1N, Fuc-5, J=6
．． 11.12.83) 4, 83 (d, l) I, F
uc-1, J=3.66) 4.96 (d, LH, F
uc-1, J = 3.21) 8.04 (d, IH, J
=9.16) Example 4 According to the following method, tetracosyl 2-acetamide 3
-〇-(α-L-fucopyranosyl〉-4-〇-[2-0
-(α-L-fucopyranosyl)β-D-galactopyranosyl]-2-deoxy-β-D-glucopyranoside(-
In the hole (1), R' = C2, H, , R2 = acetyl)
was synthesized.

(1) Tetracosyl 2-acetamide 3.4.6
-) Ku0-Cetyl-2-deoxy-β-D-glucopyranoside 500ml of methylene chloride, Molecular Sieve AW
-300Log, te)u: +t/-ru! 5. (t.

g and 2-acetamide-1 obtained in Example 1 (2),
3゜4.6-tetra-0-acetyl-2-deoxy-β
6.59 g of -D-glucobylanose was added and stirred for 10 minutes at room temperature under a nitrogen atmosphere. Next, trimethylsilyl trifler (3.28-) was added and stirred for 2 days. The reaction mixture was transferred to an ice-cooled saturated aqueous sodium hydrogen carbonate solution and stirred until no bubbles were generated. This was extracted with chloroform, washed with water, and dried over anhydrous magnesium sulfate. The solid was then filtered off, the filtrate was condensed under reduced pressure, and the resulting solid was separated and purified by silica gel column chromatography using benzene-acetone as an eluent.

5.26g (60%) of white powder was obtained.

'H-NMR spectrum (ppm) δ AM-400CDCf 3/TMS 0, 87 (t, 3H, R-CH3) 1.05 1,
45 (m, 42H, [: 82 pieces 21) 1, 50-1.
TO(m, 2H,0-CH2-CH2-R) 1.90
-2.10 (s book 4.12H, AC) 3.47 (dt
, LH, DJ: L-Ra) 3, To (ddd,
IH, L5. J4. s=9.82. Js, s□
=2.46Js, 5b=4.70Hz) 3,81 (dt, LH,H-2,J,, 2=8
．． 45. J2.3=10.29°J2. ,,=8.
52) 3, 85 (dt, IH, 0-CHz-Rb) 4, 1
3 (dd, LH, H-6a, Je-, ab=12
．． 21) 4, 26 (dd, IH, H-6b) 4, 6
9 (d, 1)1. H-1) 5, 06 (t, L
H, H-4, J3. , = 9.77) 5, 32 (t,
LH, H-3) 5,49 (d, IH, NH) (2) Tetracosyl 2-acetamide 4.6-〇-
Benziritine-2-deoxy-β-D-glucopyranoside chloroform 200mj! , 3.4°6 of tetracosyl 2-acetamide in a mixed solution of 100rnl of methanol.
5.21 g of -tri〇-acetyl-2-deoxy-β-ri-glucopyranoside was dissolved, 2.07 g of sodium methoxide powder was added at room temperature, and the mixture was allowed to react at room temperature for one day. Acidic ion exchange resin Amberly) IR-120
After neutralization by adding B, the mixture was concentrated under reduced pressure to obtain a solid. Add to this 20 g of zinc chloride (n) and 200 m of benzaldehyde.
1! was added and stirred at room temperature for 3 days. 2 each of water and hexane
50m1. was added and stirred at room temperature, and the resulting precipitate was collected by filtration and washed with hexane until the benzaldehyde odor disappeared.

After drying, 2.709 g (55%) of white powder was obtained.

'H-NMR spectrum (ppm) δ AM-400CDCl3/TMS 0, 88 (t, 3H, R-CH,) 1, 05 (, 4
5 (m, 42H, CHa*21) 1, 50-1. T
o (m, 2H,0-CH,-CH2-R)2,06
(s, 3H, Ac) 3, 19-3.60 (m, 48.8-2. H-4
,H-5,0-[')1. -Ra)3,'7B (t,
1)1. ) I-3, Js, s・Js, 4=10
．． 14) 1z) 3, 84-3.92 (rn, 1) 1
．． []-[”Hz-Rh)4, 14-4.26 Cm
, 2H,)l-6a, DH)4,18 (t, )
l-6a, JS, a, = 2.92. JS,,B
b=9.88) 4, 33 (dd, 1) 1. H-6
b, JS, 8b=4.86) 4, 71 (d, i
ll, )I-1,J,, 2=8.28)5,55
(s, IH, benzylidene-H)5, 70-5.82
(b, IH, NH)? , 30-7.59 (m,
5B, Aovtic-H) (3) Tetracosyl 2-
Acetamide 3-○-acetyl 4.6-0-benzylidene-2-deoxy-β-D-glucopyranosidetetracosyl 2-acetamido 4,6-○-benzylidene-2-deoxy-β-D-glucopyranoside 2.7
Dissolve 1g in 60ml of pyridine and add 40ml of acetic anhydride under ice cooling.
rd was added and stirred at room temperature for 1 day.

The reaction mixture was concentrated under reduced pressure, and the resulting crude product was purified using an n-hexane-chloroform mixture. 2.11 g (73%) of white solid was obtained.

'H-NMR spectrum (ppm) δ AM-400CDCl3/TMSO O, 91 (t, 3H, R-CHs) 1.20 (, 40 (m, 42H, CH, book 21) 1, 5
0(,67(m, 2H,0-CH2-CH2R)1,
95 (s, 3tl, Ac) 2,08 (s, 3H, Ac) 3,41-3.56 (m, 2H,H-5,0-Ct
l, -Ra) 3, 50 (dt, H-5, J4.S
=9.53. Js, fla=9.85゜Js, a
b=9.40Hz) 3,70 (t, 1)1. H-4, J, , ,, =
9.68) 3, 76-3.89 (m, 2H, H-6
a, 0-CH, -Rb)3,81 (t, )l-6
a, Jaa+ gb=10.44) 4,04 (dt
, 18.8-2. J r , 2=9.02. J
2. s=9.65°J2. xa=9.40>4,35 (dd, LH, J-6b)4.55 (d
, IH, H-1) 5,25 (t, LH, H-3) 5,49 (d, LH, NH) 5,5Hs, LH, benzylidene-H) 7.32-7
．． 49 (m, 5H, A07 Teitku H) (4) Tetracosyl 2-acetamido 3-〇-acetyl-6-
0-benzy-2-deoxy-β-D-glucopyranoside freshly distilled tetrahydrofuran (THF) 50 rn
l, tetracosyl 2-acetamido 3-〇-acetyl-4.6-0-benzylidene-2-deoxy-β-D
-926 mg of glucopyranoside and molecular sieve MS3-A Ig were added and stirred at room temperature for 10 minutes. 1
After adding IJ g of sodium cyanoborohydride, a saturated ethereal solution of hydrogen chloride was added dropwise until the generation of bubbles stopped. After further stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure, neutralized with the addition of sodium hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure.

The residue was separated and purified by silica gel column chromatography using chloroform-methanol as an eluent to obtain 642 μm (69%) of a white solid.

H-NMR spectrum (ppm) δ AM-400COCIJTMS 0, 87 (t, 3H, R-CL) 1, 04 (, 48 (m, 42H, CL book 21) 1, 5
0-1.70 (m, 2H,0-CH,-CH,-R
)1,92 (s, 3B, Ac) 2.06 (s, 3H, Ac) 3,34 (bs, 18.0R) 3,40-3.48 (m, IH,0-CH2-Ra
)3,55 (dt, LH,H-5,J4.s=9
．． 35. Js, s=4.60Hz)3,69 (t
, IH,H-4,Ja, 4=9.52)3,72-
3.93 (m, 5H, H-4, H-6a, H-6
b, o-ch2-flb, H2) 3, 88 (dt
, H-2, J l, 2=9.01. J2.3=9
．． 46. JL□=9.22) 4, 51 (d, IH
,H-1) 4,53-4.63 (dd, 2N, benzyl-H)
5, 08 Cdd, Ill, H-3) 5, 97 (
d, lH, NH) 7, 25-7.36 ([0,5H, aromatic-
H) (5) Tetracosyl 2-acetamido 3-0-acetyl-4-〇-(2-〇-benzoyl-3.4゜6-
)IJ-0-benzyl-β-D~galactopyranosyl)
-6-〇-benzyl-2-deoxy-β-D-glucopyranoside 2-○-benzoyl-3.4゜6-) obtained in 04) of Example 1! Dissolve 559 mg of J-○-benzyru-1-0-valanitrobenzoyl-α-D-galactopyranose in 100% methylene chloride and add 30% hydrogen bromide acetic acid solution 1.
6rnl was added and stirred at room temperature for 30 minutes.

The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous solution of hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. This residue and tetracosyl 2-acetamido 3-〇-acetyl-6-0
-Dissolve 274 mg of benzylene-2-deoxy-β-D-glucopyranoside in 25-methylene chloride, add 3003 g of molecular sieve AW-300, and 0.105 g of tetramethylurea.
- was added and stirred at room temperature for 10 minutes. 225 mg of silver trifler was added thereto and reacted at room temperature for 19 hours.

The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous solution of hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and subjected to reduced pressure. The residue was purified by column chromatography using benzene-ethyl acetate as an eluent to obtain 204.5μ (42%) of a white powder.

'H-NMR spectrum (ppm) δ AM-400CDCfa/TMS 0, 89 (t, 3H, R-CH3) 1.08-1.
48 (m, 42H, 2 CH 21) 1, 48-1.60
(m, 2H,0-CH,-CH,-R)1.92
(s, 3tl, Ac) 1,99 (s, 38.AC) 3,20-3.27 (m, LH,0-CL-Ra)
3, 38 (dt, LH, H-5, J4. s=7.
78. Js, s”3.83.7.72Hz)3,4
4-3.72 (m, 7H, H-3', H-5°
, H-6a, H-6°a, H-6b.

H-6°b, 0-CH2-Rb) 3,91 (t, LH,H-4,J3.4=8.30
)4,00 (d, 1)1. H-4°+J3・1・
=2.36)4,04(q,l)1. H-2, Jl
, 2=8.73. Jz, 3=9.11°J2. −
a: 9.42) 4.19 (d, IH, H-1) 4, 25-4.98 (m, IOH, H-1',
H-3, benzyl-H) 4.52 (d, H-1', J
l, 1 = 7.93) 4, 95 (t, H-3) 5, 50 (dd, IH, H-2', Jl, ・= 10
．． 05) 5,73 (d, IH, NH) 7,00-8.00 (rn, 25H, A07 Teitku H) (6) Tetracosyl 2-acetamido 4-〇-(3,4,6-) Lee○ -Benzyl-β-D-galactopyranosyl)-6-0-benzyl-2-deoxy-β
-D-glucopyranoside A mixture of 100 ml of chloroform and 50 methanol was added with tetracosyl 2-acetamido 3-〇-acetyl-4-〇-(2-○-benzoyl-3.4.6-)-0-benzyl-β-D-galacto. Pyranosyl)-6-0
200 mg of -benzyl-2-deoxy-β-D-glucopyranoside was added, 1 g of sodium methoxide was added thereto, and the mixture was stirred at room temperature for 1 day. After stopping the reaction by dropping 2rnl of acetic acid, it was concentrated, the residue was poured into an ice-cooled saturated aqueous sodium bicarbonate solution to neutralize it, and extracted with chloroform.
It was dried using magnesium sulfate and concentrated under reduced pressure.

This was purified by column chromatography using benzene-ethyl acetate as the eluent to obtain 117 mg (6
7%) obtained.

'H-NMR spectrum (ppm) δ AM-400CDCji! , /TMSO,91(t,
31 (, R-C) 13) 1.08-1.48 (m, 4
2H, CL book 21) 1.50-1.65 (m, 2t1
．． 0-CH,-CH,-R)1,99 (s, 3H,
Ac) 3, 13-3.66 (m, 9H, tl-5, H-2
', H-3', H-5°, H-6a, tl
-6' a.

0-CH2-Ra, OH book 2) 3, 34 (dd, H-3°, J2', a'
=9.73. J3', 4" = 2.73Hz) 3
．． 70-4.05 (m, 6H,H-2,H-4,H
-6b, H-4', H-6'b.

Low CL-Rb) 4.23 (d, IH,)l-1,J,, 2=7.
75) 4, 31-4.90 (m, 9H, H-1'
, benzyl-H) 4.74 (d, H-1', J,', 1
=8.29)5.74(d, IH,NH,J2.w
++=7.54) 7, 04-7.60 (m, 20H
, A07te4''/Kuh) (7) Tetracosyl 2-acetamido-6-0-benzyl-3-0-(2,3,4-
) Li○-benzyru α-L-fucopyranosyl)-4-
0-(3゜4.6-1-Lee ○-Benzyru 2-0-(
2,3,4-triO-benzy-α-L-fucopyranosyl)-β-D-galactopyranosyl]-2-deoxy-
β-D-glucopyranoside obtained with αO of Example 1 2, 3.4-) IJ-○-
Benzyl-6-zooxy-1-0-paranitrobenzoyl-α or -β-L-galactopyranose 316 ■ methylene chloride 50 In! ! 500 μm of molecular sieve MS3A was added, and the mixture was stirred at room temperature for 10 minutes. 10 ml of 30% hydrogen bromide and acetic acid solution was added thereto and reacted for 10 minutes. The reaction solution was cooled with ice-cooled saturated hydrogen carbonate) I
Neutralize by pouring into an aqueous solution of Jum and extract with chloroform.
It was dried using magnesium sulfate and concentrated under reduced pressure. This residue and tetracosyl 2-acetamide 4-0-(3
, 4,6-tri〇-benzyl-β-D-galactopyranosyl)-6-0-benzyl-2-deoxy-β-rucobyranoside (117) was converted into benzene-nitromethane (1).
:1 Dissolved in a mixture of 30- and molecular sieve AW-3.
001g was added and stirred at room temperature for 10 minutes. 253 μm of mercury(II) cyanide was added thereto, and the mixture was allowed to react at room temperature for 38 hours. The reaction solution was neutralized by pouring it into an ice-cooled saturated aqueous solution of hydrogen carbonate, extracted with chloroform, dried over magnesium sulfate, and concentrated under reduced pressure. This residue was purified by column chromatography using benzene-ethyl acetate as the eluent, and a pale yellow glass was purified with 120 μg (58
%)Obtained.

'H-NMR spectrum (ppm) δ AM-400CDC1,/TMS 0.88 (t, R-[')1. ) 1, 10 (d, Fuc-6, J=6.37Hz) 1
, 14-1.33 (m, CH2*21. Fuc-
6) 1,40-1.62 (m, a-CH2-CI(
2-R, to C) 2.97 (m, GlcNAc-2,
J=7.61) 3.20 (bs, Fuc-4) 3.27 (bd, GlcNAc-5, J=9.37
) 3, 34 (dd, Ga 1-5. J=4.96
．． 8.42>3.41-3.48 (m, 0-CL-
Ra) 3, 53 (dd, Ga1-3. J=2.7
1.9.52) 3, 59-3.69 (m, GlcN
Ac-6a, Ga1-6a, Puc-4)3, 72
(t, Ga 1-6b, , b8.32) 3.75
-3.83 (m, GlcNAc-6b, Fuc-
3,0-CH2-Rb)3,87 (dd, Fuc-
3,, h2.30.10.87) 3, 92-3.98
(m, GIcNAc-4, Ga1-4.benzyl-H
)3,98-4.12 (m, Puc-2,Ga1-
2. Puc-2) 4, 21 (t, GIcNAc-
3, J=9.31) 4, 29 (dd, Fuc-5,
,b6.12.12.23)4,33-5.02 (m
, benzyl-H, Ga1-1. Fuc-5, Fuc-
1) 4, 47 (d, Ga1-1. J=5.06)
4,89 (d, Puc-1, J=3.70)5,1
4 (d, G 1cNAc-1, J = 7.95) 5,
58 (d, NH, J=6.54>5, 67 (d,
Fuc-1, J = 3.74) 6, 90-7.60 (
m, aromatic-H) (8) Tetracosyl 2-acetamido 3-〇-(α-L-7 cobylanosyl)-4-
0-[2-○-(α-L-fucopyranosyl)-β-D-
Galactopyranosyl]-2-deoxy-β-ri-glucopyranoside tetracosyl 2-acetamido-6-〇-benzyl 3
-0-(2,3,4-)LeeO-benzyl-α-L-fucopyranosyl') -4-0-(3,4,6-)LeeO
-benzyru-2-0-(2,3,4-tri〇-benzyru-α-L-fucopyranosyl)-β-D-galactopyranosyl]-2-deoxy-β-D-glucopyranoside 1
10 ml of methanol was added to 19 ml, 1 g of 10% palladium on carbon and 4 ml of formic acid were added, and the mixture was reacted at room temperature for 4 hours. The reaction mixture was filtered using a filter aid and concentrated under reduced pressure to obtain 57.3 square meters (91%) of a slightly yellow glass.

'H-NMR spectrum (ppm) δ AM-4000M5O-d, /TMS 0.85 (bs, R-CH=) 1,04 (d, Fuc-6, J=5.31Hz) 1
, 08 (d, Puc-6, J=5.51) 1, to
(, 35 (m, CHi book 21) 1.35-1.50 (
m, low CH2-CL-R) 1,78 (s, Ac) 3,05-3.85 (re, ring-H,0-[”H
z-R) 3, 96-4.05 (m, Fuc-5) 4
, 33 (d, GlcNAc-1, J = 7.48) 4
, 42 (d, Ga1-1. J=4.90) 4, 6
4-4.73 (m, Fuc-5) 4,83 (bs
, Fuc-1) 4,95 (bs, Fuc-1) 8,00 (d, NH, J=8.18) or more

Claims (1)

[Claims] 1. The following general formula (I) ▲There are numerical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R^1 represents an alkyl group having 3 to 30 carbon atoms,
R^2 represents a lower alkanoyl group] A sugar chain-related antigen derivative represented by: