JPS582959B2 - Benzylated sugar derivative - Google Patents

Description

[Detailed description of the invention] The present invention is based on the general formula: (However, in the formula, Bn represents a benzyl group.

) The present invention relates to a novel benzylated sugar derivative shown in

Sugars are generally a group of compounds in which all of the asymmetric carbon atoms have hydroxyl groups.

Differences in reactivity are known among these numerous hydroxyl groups,
Utilizing this, various chemical transformations have been carried out by partially protecting hydroxyl groups and further reacting the unprotected hydroxyl groups, but if these many hydroxyl groups are regioselectively activated, even more Effective and efficient chemical conversion becomes possible.

As a result of intensive research from the above viewpoint, the present inventors have obtained new knowledge that the sugar derivative of the present invention can be obtained in a high yield and regioselectively under mild reaction conditions, and have completed the present invention. Ta.

The sugar derivative of the present invention is expected to be used as a synthetic intermediate for branched oligosaccharides, a food additive as a sugar ester, a synthetic intermediate for various antibiotics, and a synthetic intermediate for macrolide compounds.

For example, it is known that various polysaccharides inhibit the growth of allogeneic tumors when transplanted into mice, and that D-mannan from various yeasts exhibits similar antitumor properties.

Although the correlation between the chemical structure of these polysaccharides and their antitumor activity has not yet been clarified, their main chains are α-(1→6)-
D-mannopyranosyl residues, and the majority of the branched chains are found to consist of α1(1→2) and α1(1→3)1 D-mannopyranosyl residues.

The compound of the present invention, for example, methyl 2,4-di-0-benzyl-α-D-mannopyranoside (5), is used as a synthetic intermediate for oligomannoside, which becomes the basic sugar chain structure in the synthesis of high mannose type polysaccharide having the above sugar chain structure. Useful.

This is illustrated below. Next, the method for producing the sugar derivative of the present invention will be described in detail.

First, starting materials include methyl α-D-mannobyranoside and methyl β-D-galactobyranoside.

The reaction between the starting material and bis(trialkyltin) oxide is carried out by adding bis(trialkyltin) oxide to the sugar derivative and heating and refluxing the mixture in an organic solvent under dehydration conditions.

As the bis(trialkyltin) oxide used, bis(trialkyltin) oxide having a C1 to 07 alkyl group as the lower alkyl group can be used, such as bis(triethyltin) oxide, bis(trimethyltin) Oxide, bis(tri-n-butyltin) oxide, bis(tri-n-propyltin) oxide, etc. can be used.

The amount of the bis(trialkyltin) oxide to be used is preferably 0.1 to 3 times the number of hydroxyl groups in the starting material to be converted, preferably 0.5 to 0.8 times the molar equivalent.

Since this reaction is reversible, the reaction can proceed advantageously by removing the water produced from the system.
The alkyl tin compound can be quantitatively obtained by carrying out the reaction while removing water under reflux using a take-up solvent such as toluene, benzene, carbon tetrachloride, cycloethane, tetrachlorethane, etc.

The reaction temperature and reaction time at this time vary depending on the reagents, solvents, etc. used, and are not particularly limited.
00 hours, preferably 1 to 30 hours at 60 to 150°C.

Since the reaction product is unstable to moisture in the air, it can be used in the next reaction without being isolated or purified.

The trialkyltin compound thus obtained is reacted with an allyl-forming agent such as allyl chloride, allyl bromide, allyl iodide, etc. in an organic solvent or without using a solvent.

The amount of the allylating agent used is preferably 1 to 10 times the molar equivalent of the amount of the bis(trialkyltin) oxide used.

As the solvent, take-out solvents such as toluene, benzene, carbon tetrachloride, cycloethane, tetra-take ethane, etc. can be used, but the allylating agent may be used in large excess as a solvent to carry out the reaction directly. I can do it.

The reaction temperature and reaction time are not particularly limited, but each -
A suitable temperature is 20 to 140°C for 1 to 200 hours.

The allylated sugar derivative thus obtained is reacted with a benzylating agent such as benzyl bromide or penzyl chloride.

At this time, it is desirable to react the benzylating agent in the presence of a hydrogen halide scavenger, such as a base such as sodium hydride, potassium hydroxide, barium hydroxide, or the like.

[J. S. Brimacombe, Methods i
n Carbohydr. Chem. , 6 (1972)
376-378] As the solvent, for example, dimethylformamide, tetrahydrofuran, dioxane, etc. can be used, and the reaction temperature and reaction time are preferably -20 to 40°C and 30 minutes to 48 hours, respectively.

Then, the allyl group of the obtained allylated benzylated sugar derivative is removed.

That is, when the above-mentioned allylated benzylated sugar derivative is reacted in a solvent containing alcohol in the presence of Pd-C, the target deallylated sugar derivative can be obtained.

Next, the present invention will be explained by giving specific examples.

Methyl-α-D-mannopyranoside (1) was refluxed with 1.5 mol (3 equivalents) of bis(tributyltin) oxide in toluene at 140°C for 4 hours while removing water, and then the toluene was distilled off. An oily substance is then obtained.

This was mixed in a large excess of arylf hepamide under a nitrogen atmosphere.
Heating is carried out at 0°C for 7 days.

The reaction product was subjected to silica gel column chromatography (C
H2Ct2-acetone) and purification yields methyl 3,6-di-0-aryl-alpha-D-mannopyranoside (
2) and methyl 3-0 aryl α-D-mannopyranoside (3) were obtained in yields of 71% and 13%, respectively.

When the compound (2) is reacted with sodium hydride and benzyl bromide in dimethylformamide at -10°C for 2 hours, methyl 3,6-diO~aryl2,
4-di-O-benzyru-α-D-mannopyranoside (4
) was obtained almost quantitatively.

Next, the compound (4) was mixed with ethanol-acetic acid monohydrate (2
:1:1) Reaction using a catalytic amount of 10% Pd-C in a mixed solvent yields the target methyl 2,4-di-0-benzyl-α-D-mannopyranoside (5) in a yield of 53%. .

Similarly, methyl β-D-galactopyranoside (6
) is stannylated and then reacted in allylbamide to form methyl 3,6-diO-allyl β-D-galactopyranoside (7) and methyl 610-allyl β-D.
- Galactopyranoside (8) with a yield of 51% and 1
1%, and further benzylation of compound (7) yields methyl 3,6-diO-allyl-2,4-di0-benzyl-β~D-galactopyranoside (9), followed by removal of the allyl group. When carrying out
) in an overall yield of 31%.

This can be expressed in a diagram as follows.

Among the compounds in the figure, (2), (3), (4), (5)
, (7), (8), (9), and (10) are all new compounds.

The present invention will be explained in detail below using examples.

Example 1 Methyl α-D-mannopyranoside (1) 402 mg (1
mmol) and bis(tri-n-butyltin) oxide8
93 (1.5 mmol) was dissolved in toluene and refluxed at 140° C. for 4 hours while removing distilled water, and the toluene was distilled off.

The resulting oil was dissolved in a large excess of allyl bromide (10
ml) and heated at 80° C. for 7 days under a nitrogen atmosphere.

The reaction product was subjected to silica gel column chromatography (C
After separation and purification with H2Cl2-acetone), methyl 3,6-di-0-allyl α-D-mannopyranoside (2)[α]D+29.6° (Ω1.6)) and methyl 3-0-allyl α-D-mannopyranoside (3) [[
α)D+51.4°(C0.93): ]34 each
9■ (yield 71%) and 58■ (yield 13%) were obtained.

Example 2 Compound (2) obtained in Example 1 was reacted in dimethylformamide with excess benzyl bromide in sodium hydroxide at -10°C for 2 hours, and then purified by chromatography to obtain methyl 3,6 -G0-Arylu2
,4-di-O-benzyl~α-D-mannopyranoside (
4) [α], +33.5° (Ω0.55)) is obtained quantitatively.

Example 3 Compound (4) obtained in Example 2 was purified by chromatography by treatment with a catalytic amount of 10% Pd-C in ethanol-acetic acid monohydrate (2:1:1). After that, crystallization from isopropyl ether gave methyl 2,4-
Di-0-benzyru-alpha-D-mannopyranoside (5) [
[α]D+23.5°(C0.77)] was obtained by 321mg.

(Total yield from compound (1) 53%) Example 4 Methyl β-D-galactopyranoside (6) 402 mg (
Tributyltin formation was carried out in the same manner as in Example 1 using 1 mmol), and then reacted with allyl bromide to form (
80-85°C for 8 days), chromatographic separation and purification was performed to obtain methyl 3,6-di-0-aryl-β-D-
Galactopyranoside (force [[α]D + 1.3° (C0.
60)] and methyl 6-0-aryl β-D-galacto.
Pyranoside (8) ([α]D-23.0° (C0.90
) were obtained in amounts of 251 mg (yield 51%) and 49 mg (yield 11%), respectively.

Example 5 Compound (7) obtained in Example 4 was reacted and purified in the same manner as in Example 2.

Methyl 3,6-di-0-aryl-2,4-di-0-benzyl-β-D-galactopyranoside (9) [[α]D-
9.9° (C0.90) was quantitatively obtained.

Example 6 Compound (9) obtained in Example 5 was subjected to reaction, separation and purification, and crystallization in the same manner as in Example 3 to obtain methyl 2,4-di0
-benzyru β-D-galactopyranoside (16) [[
α]D-10.6° (C0.41), m. p. :144
~146°C) 188 mg (total yield 31 from compound (6)
%)Obtained.

Claims (1)

[Claims] 1. A benzylated sugar derivative represented by the general formula: (wherein, Bn represents a benzyl group). 2. The benzylated sugar derivative according to claim 1, which is 2-methyl 2,4-di-0-benzyl-α-D-mannopyranoside. 3. The benzylated sugar derivative according to claim 1, which is methyl 2,4-di-0-benzyl-β-D-galactopyranoside.