JPH01249796A - Preparation of phenol glycosides - Google Patents

Abstract

PURPOSE:To provide the subject compound, a plant medical ingredient, in a high yield without yielding any by-product, by reacting an acylated saccharide compound with a phenol having an alcoholic OH group on the phenyl ring thereof the presence of a specific catalyst. CONSTITUTION:An acylated saccharide compound and a phenol of formula I (R is H or methyl) (e.g., salicyl alcohol) are subjected to a glycosidation reaction in the presence of a heteropolyacid (preferably 12-tungstophosphoric acid) to provide the objective compound of formula II (G is acylated saccharide residue). The acrylated saccharide compound and the phenol are preferably in a molar ratio of 1:1-2.5. The amount of the heteropolyacid used is preferably 0.5-1wt.% of the total amount of the acylated saccharide compound and the phenol.

Description

[Detailed description of the invention] The present invention relates to a method for producing phenol glycosides.

Conventional technologies and their problems In recent years, herbal medicines derived from plants have attracted attention due to their medicinal efficacy.
Since the amount of medicinal ingredients contained in plants varies depending on the weather and other factors, it is desired to stably supply these medicinal ingredients through synthesis.

A considerable portion of medicinal ingredients present in plants are phenol glycosides, which are glycosidic bonds of phenols having an alcoholic OH group on the phenyl ring and sugars.

Conventionally, when synthesizing phenol glycosides,
For example, glycosidation of acetohalogen moieties in the presence of acid scavengers such as A g 20 sHg(CN)2, glycosidation of acylated sugars and phenyl rings in the presence of catalysts such as p-toluenesulfonic acid, ZnCQ2, etc. A method of glycosidation reaction with phenols having an alcoholic OH group has been carried out.

However, in the above method, it is extremely difficult to selectively glycosidate only the phenol position, so a large amount of by-products in which alcoholic OH groups are glycosidated are produced, and the target product, phenol glycosides. Yield is low. Moreover, large amounts of ring-expanded decomposition products, sugar chain decomposition products, browning products, etc. of the sugar compounds used as raw materials may be produced as by-products.

In that case, isolation and purification of the obtained phenol glycosides becomes extremely difficult due to the presence of large amounts of by-products.

In order to overcome these drawbacks, a method of selectively protecting only the alcoholic OH group has been carried out, but this method requires complicated operations and the yield is not sufficient.

Problems to be Solved by the Invention An object of the present invention is to provide a method for selectively glycosidating only the phenol position of phenols having an alcoholic OH group on the phenyl ring to obtain phenol glycosides in high yield. It's about doing.

Means for Solving the Problems The object of the present invention is to prepare an acylated sugar compound in the presence of a heteropolyacid, and a compound of the general formula [wherein R represents a hydrogen atom or a methyl group]. ] is subjected to a glycosidation reaction with a phenol represented by the general formula [wherein R is the same as above]. G represents an acylated sugar residue. ] This is achieved by a method for producing phenol glycosides, which is characterized by synthesizing phenol glycosides represented by the following.

As a result of intensive research, the present inventors have found that heteropolyacids exhibit a remarkable catalytic effect on the glycosidation reaction of phenols of the above general formula (1), leading to the formation of by-products in which alcoholic OH groups are glycosidated, and ring-expanding decomposition. It has been found that the target phenol glycosides can be obtained in high yield without producing by-products such as sugar chain decomposition products, sugar chain decomposition products, and browned sugar products. Furthermore, the method of the present invention has the advantage that the obtained phenol glycosides can be easily isolated and purified since no by-products are produced.

As the heteropolyacid used as a catalyst in the present invention, known ones can be used, for example, the following general formula (3
) Keggin structure heteropolyacids and the like can be mentioned.

HYMr2040 Function b H20(3) [wherein, Y is P
, As, Si or Ge. M represents Mo or W.

a indicates 3 or 4.

(However, when Y is P or As, a=3, and Y is Si
or when Ge, a=4). b represents an integer from 0 to 30. ] As a specific example of the heteropolyacid represented by the above general formula (3), for example, phosphotungstic acid (H3PWI20t
o-bH20), phosphomolybdic acid (H3PMo1
2040 bH20), silicotungstic acid (H
A S 1WI204°・bH20), silicomolybdic acid (H4SiMo, 204o・bH20), arsenic tungstic acid (H3AsW+204o-bH20), arsenic molybdic acid (H3AsMoI2o, O" bH20)
, germanotungstic acid (H4GeW12040
* bH20), germanomolybdic acid (H4G e
Mo, 2040-bH20), etc.

In the present invention, considering the stability as a catalyst, among the above-mentioned heteropolyacids, for example, 12-tungstophosphoric acid, 12-molybdophosphoric acid, 12-tungstosilicic acid, 12-molybdosilicic acid, etc. can be particularly preferably used. .

These heteropolyacids can be used alone or in combination of two or more, and can be used as an insoluble catalyst by being supported on silica gel, alumina, activated carbon, or the like. Supporting may be carried out in accordance with a known method; for example, the carrier may be added to a solution of the heteropolyacid in water or a polar low-boiling solvent, thoroughly mixed, and then dried under reduced pressure. The supported amount is not particularly limited and may be selected as appropriate, but it is usually about 5 to 50% of the weight of the carrier. Furthermore, these heteropolyacids can also be used in combination with conventionally used catalysts such as para-toluenesulfonic acid and ZnC92.

In the present invention, any known saccharide can be used as the raw material sugar compound, such as monosaccharides, polysaccharides, oligosaccharides, etc. Representative examples of monosaccharides include hexoses such as glucose, mannose, galactose, glucosamine, mannosamine, and galactosamine, and coal sugars such as arabinose, xylose, and ribose.

Representative examples of oligosaccharides include lactose, trehalose, maltose, cellobiose, isomaltose, gentiobiose, laminaribiose, chitobiose, xylobiose, mannobiose, sophorose, maltotriose, maltotetraose, and hydrolysates of starch, cellulose, etc. etc. can be mentioned. Typical examples of polysaccharides include chitin, chitosan, starch, cellulose, and the like. Furthermore, the sugar compounds include derivatives of the above-mentioned monosaccharides, oligosaccharides, and polysaccharides, such as sugar esters, glycosides, and the like.

Particularly preferred sugar compounds in the present invention include, for example, glucose, galactose, mannose, maltose, and lactose.

In acylating the above-mentioned sugar compound, conventionally known methods such as Fisher's method (E.

Fisher's method (Chem, Berr.).

49.584 (1916)) etc. For example, glucose noacylation is carried out by mixing finely powdered anhydrous glucose and anhydrous sodium acetate and heating the resulting mixture with stirring. The monovalent residue of the acylated sugar compound becomes the sugar residue represented by the symbol G in the above general formula (2).

In the present invention, the above general formula (1) is subjected to a glycosidation reaction with an acylated sugar compound in the presence of a heteropolyacid.
The phenols represented by are known compounds, for example, according to the method of Adkins et al. [J, Am, C
hem, Soc,.

52.4349 (1930)) etc. Specific examples include salicyl alcohol,
p-hydroxybenzyl alcohol, 2-hydroxy-
Examples include 4-methyl-benzyl alcohol.

The reaction between the acylated sugar compound and the phenol of general formula (1) is carried out in the presence of a heteropolyacid without a solvent or in a suitable solvent. The ratio of the acylated sugar compound and phenol to be used is not particularly limited and may be selected as appropriate, but usually the latter is about 1 to 10 times the mole of the former, preferably 1 to 2.5 times the mole. Just use it to a certain degree. The amount of heteropolyacid used is also not particularly limited, but it is usually 0.00% of the total amount of acylated sugar compound and phenol.
It may be about 1 to 5.0% by weight, preferably about 0.5 to 1.0% by weight. The above reaction is carried out at a temperature of about 20 to 180°C for about 1 to 24 hours. Further, the reaction pressure can be appropriately selected within the range of normal pressure to 1 mmHg reduced pressure.

The anomer ratio of the obtained phenol glycosides can be arbitrarily selected by changing the pressure or by changing the type of heteropolyacid. Suitable solvents for the above include hexane, heptane, octane, jsOP
Saturated hydrocarbons such as ER (trade name, manufactured by Esso Oil Co., Ltd.), aromatic hydrocarbons such as toluene, xylene, mesitylene, ethylbenzene, laurylbenzene, ketones such as acetone, diethyl ketone, methyl isobutyl ketone, acetic acid Examples include esters such as butyl and ethyl butyrate, ethers such as diethyl ether and isopropyl ether, and diethylene glycol dialkyl ethers such as ethylene glycol dibutyl ether and diethylene glycol dibutyl ether.

In this way, a phenol glycoside represented by the general formula (2) in which the phenol position of the phenol of the above general formula (1) is selectively glycosidated can be obtained. The phenol glycosides are isolated and purified from the reaction mixture by conventional purification means.

Effects of the Invention According to the production method of the present invention, there is no generation of by-products as observed in conventional glycosidation reactions, and the desired phenol glycosides can be selectively obtained in high yield.

Moreover, the obtained phenol glycosides can be easily isolated and purified.

EXAMPLES Examples and comparative examples are given below to make the present invention even clearer.

Example 1 8.0 g of pentaacetyl β-D-glucopyranosulfate
(0.20 mol) and salicyl alcohol 49.6 g
(0.40 mol) was dissolved in diethylene glycol dibutyl ether 150n+2 and heated to 100°C. Add 1.0 g of 12-molybdophosphoric acid to this solution, and add 20 m
The reaction was carried out for 2.5 hours while removing the acetic acid produced at 100 to 110° C. under reduced pressure of mHH.

Add 150 mQ of ethyl acetate to the reaction solution, and add 0.1M Na
It was washed three times with 50 mQ of OH and twice with 50 mG of water, and the organic layer was concentrated under reduced pressure. Hexane was added to the residue, and the precipitated crystals were separated in a furnace, and the obtained crystals were further recrystallized from hot ethanol to obtain 58.1 g of tetra-O-acetylsalicin (yield: 64%).

Comparative Example 1 The reaction was carried out in the same manner as in Example 1 except that 1.0 g of p-toluenesulfonic acid was used as a catalyst. The main product was 16.4 g of tetra-O-acetyl salicin.
(18,0%) and 0-hydroxybenzyl-2,3,
It was a mixture of 11.63 g (12.8%) of 4,6-Chitler O-acetyl-D-glucopyranoside, and the target product, tetra-O-acetyl salicin, could not be isolated.

Comparative Example 2 13.6 g (0.11 mol) of salicyl alcohol and 25.6 g of silver oxide in 100 mQ of dehydrated chloroform
(0.11 mol) and shielded from light, acetobromoglucose 41.0g (0.10 mol) and chloroform 10
The 0+nQ solution was added dropwise over 1 hour while stirring. After further stirring at room temperature for 8 hours, the precipitated solid matter was removed and the furnace solution was diluted twice with 100 mQ of 4% sodium bicarbonate solution. 2 with water
Washed twice.

Ether-petroleum ether was added to the residue obtained by distilling off the chloroform layer under reduced pressure to obtain a solid.

The composition of the solid is tetra-0-acetyl salicin 20
．． 9 g and 0-hydroxybenzyl-2,3°4.6-chitler O-acetyl-β-D-glucopyranoside 14.
It was 3g of mixture. This was purified by silica gel chromatography (eluent: hexane:ethyl acetate = 3:2), but only 14.5 g (yield: 32%) of the target product, tetra-0-acetylusalicin, was obtained.

Example 2 Pentaacetyl β-D-glucobylanose 39°0g
(0.10 mol) and 24.8 g (0.20 mol) of p-hydroxybenzyl alcohol were dissolved in 80 m of diethylene glycol dibutyl ether (2) and heated to 100°C. To this solution was added 0.5 g of 12-tungstophosphoric acid. In addition, the mixture was reacted for 2 hours while removing acetic acid produced at 100°C to 110°C under a reduced pressure of 20 mmHg.

The reaction solution was treated in the same manner as in Example 1 to obtain 26.4 g of p-hydroxymethylphenyl-2,3,4,6-chitler O-acetyl-α-D-glucopyranoside (yield: 5
8.1%).

Comparative Example 3 When the reaction was carried out in the same manner as in Example 2 except that 25.0 g of ZnCQ was used as a catalyst, the yield of the target phenyl glucoside was extremely low at 5.1 g (yield 11.3%), and the structure A large amount of unknown brown matter was formed as a by-product.

Example 3 Pentaacetyl β-logalactose 39.0g (0,
10 mol) and 27.8 g (0.20 mol) of 2-hydroxy-4-methyl-benzyl alcohol in 15 OPE
RG (trade name, manufactured by Esso Oil ■) dissolved in 150 mQ,
It was heated to 110°C.

Add 0.7 g of 12-tungstosilicic acid to this solution and
The reaction was carried out at 115° C. for 4 hours under reduced pressure of mmHg. Add 100 mQ of ethyl acetate to the reaction solution and dilute to 100 rll12
After washing twice with water, ethyl acetate was distilled off under reduced pressure.
The residue was left at 0°C overnight. After the crystals containing the precipitated oil-like substance were separated by furnace, the crystals were further recrystallized with hot ethanol to obtain 2-hydroxymethyl-5-methylphenyl-2.
'13'14', 6'-tetra-0-acetyl β
-D-galactopyranoside 23.0g (yield 49.3%
) was obtained.

(that's all) ゝ・〜’−;−’

Claims (3)

[Claims] (1) In the presence of a heteropolyacid, there is an acylated sugar compound and the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R represents a hydrogen atom or a methyl group. ] is subjected to a glycosidation reaction with phenols represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R is the same as above. G represents an acylated sugar residue. ] A method for producing phenol glycosides, which comprises synthesizing phenol glycosides represented by: (2) The heteropolyacid has the general formula H_aYM_1_2O_4_0・bH_2O [wherein, Y
represents P, As, Si or Ge. M represents Mo or W. a represents 3 or 4. (However, when Y is P or As, a=3, and Y is Si
or when Ge, a=4). b represents an integer from 0 to 30. ] The manufacturing method according to claim 1, which is a Keggin structure heteropolyacid represented by: (3) The heteropolyacid is phosphotungstic acid, phosphomolybdic acid, silicotungstic acid, silicomolybdic acid,
The manufacturing method according to claim 1, which is one or more selected from arsenic tungstic acid, arsenic molybdic acid, germanotungstic acid, and germanomolybdic acid.