JPH0219332A - Collection of l-quebrachitol contained natural rubber serum - Google Patents

Abstract

PURPOSE:To provide L-quebrachitol by adding an acetylating agent to a natural rubber serum to acetylate the quebrachitol contained in the serum, separating the acetylated quebrachitol with a silica gel column and subsequently hydrolyzing the separated acetylated quebrachitol for a deacetylations reaction. CONSTITUTION:An acetylating agent (preferably acetic anhydride) is added to a natural rubber serum and subjected to an acetylation reaction at 30-120 deg.C for 5hr with stirring. A dehydrating agent such as concentrated sulfuric acid or zinc dichloride and a base such as pyridine are preferably used as reaction auxiliaries is the reaction. The reaction solution is subjected to a solvent extractions to remove impurities contained therein, washed with an alkali solution, passed through a silica gel column for the purification thereof and subsequently subjected to a hydrolysis reaction using an acid (e.g. hydrochloric acid or sulfuric acid) or base (e.g. NaOCH3) as a catalyst to deacetylate the acetylated product. The hydrolysis reaction is performed by heating and refluxing the purified solution is an oil bath of 100-150 deg.C for 10-20hr. The subject substance is useful as a physiologically active substance or an intermediate thereof.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention is directed to the production of L-quebrachytol (L-(-)-2-0-Metyl-chiro-i) contained in natural rubber serum.
1 tol)).

<Prior art> L-quebrachitol is a monomethyl ether of inositol, and is
It is widely found in the sap of A. brastliensis and other plants.

Inositol is a cyclohexanehexol with six hydroxyl groups on the cyclohexane ring, and there are nine stereoisomers, but myo-inositol is the most abundant in nature. It exists as phosphatidylinositol in animals and plays an important biochemical role. Additionally, some of its derivatives are constituents of useful antibiotics. For this reason, research on the synthesis of inositol conductors for biological activity, such as the synthesis of inositol phosphate esters, is actively being conducted.

L-Quebrachytol is an optically active inositol, and as mentioned above, it has the potential to function as a physiologically active substance in living organisms, and is a substance that can be used as a useful synthetic raw material in research and development of pharmaceuticals and agricultural chemicals. Until now, it has not been collected in mass production as an industrial raw material such as a synthetic raw material, and therefore it has not been supplied industrially at all to date.

<Problems to be Solved by the Invention> As mentioned above, no method has been found for mass producing L-quebrachytol as an industrial raw material such as a synthetic raw material.

Therefore, the present invention aims to mass-produce L-quebrachytol by effectively utilizing natural rubber serum, which has conventionally been discarded as waste liquid.

<Means for Solving the Problems> The present invention solves the above problems by developing a method for collecting L-quebrachytol contained therein from natural rubber serum.
Disclose.

The present invention provides a method for collecting L-quebrachytol contained in natural rubber serum, which comprises separating and collecting L-quebrachytol contained in natural rubber serum by acetylation treatment.

Furthermore, an acetylating agent is added to the natural rubber serum to acetylate L-quebrachytol in the serum, and the acetylated product is separated using a silica gel column, and then hydrolyzed with an acid or base to deacetylate it. A method for collecting L-quebrachytol contained in natural rubber serum is shown.

The present invention will be explained in detail below.

The raw material used in the present invention is natural rubber serum. Natural rubber serum is an aqueous solution that remains after removing the coagulated rubber during the natural rubber manufacturing process. This contains small amounts of non-rubber components such as proteins, nitrogen compounds, sugars, and ash. L-quebrachitol, which is to be collected in the present invention, also exists as one of the above-mentioned saccharides.

However, the nature of the natural rubber serum used in the present invention is that of a concentrated product (
Concentrated liquids) or dried powders are preferred.

Regarding such powdery non-rubber components, Japanese Patent Application No. 1986-
It is disclosed in No. 313612.

L-quebrachytol in the concentrate or solid substance (hereinafter referred to as solid residue) of the natural rubber serum is acetylated with an acetylating agent. Examples of the acetylating agent include acetyl chloride and acetic anhydride, with acetic anhydride being preferred because it is easy to handle.

The amount of the acetylating agent added must be sufficient to acetyl-substitute all the hydroxyl groups of L-quebrachytol present, and a large amount of the acetylating agent may be used.゛
Specifically, for L-quebrachitol f moIl contained in the solid residue, acetic anhydride of 5a+oj2 or more,
5 maft or more of acetyl chloride, etc. is required.

Although the reaction temperature and reaction time vary depending on the acetylating agent used, in the case of acetic anhydride, it is preferable to heat the reaction at 30 to 120° C. for 5 hours or more while stirring.

Solid residue 1 kgk as an additive in addition to acetyl and other agents
It is preferable to use concentrated sulfuric acid with a concentration of around 100 mJZ per m, a dehydrating agent such as zinc chloride with a ratio of around 103, or a base such as pyridine with a ratio of around 31 per kg of solid residue as a reaction aid.

It is preferable to remove other impurity components contained in the reaction solution after the acetylation. In addition to acetylated L-quebrachytol (penta-0-acetylquebrachytol), the solid residue also contains α-globulin, hevein, metal compounds such as potassium, magnesium, and copper as protein components. This is because there is.

Methods for removing impurities include solvent extraction and the like.

The solvent extraction method, solvent, etc. may be carried out in the same manner as in the purification of L-quebrachytol described later.

Impurities can be further removed by washing the extraction solvent with acid or alkali.

For acid or alkali cleaning, the solution is not particularly limited, but as the pickling liquid, hydrochloric acid, nitric acid, aqueous sulfuric acid, etc. are preferable, and as the alkaline washing liquid, sodium bicarbonate, sodium hydroxide aqueous solution, etc. are preferable. Washing with water or saline may also be used.

The organic phase after the above-mentioned washing needs to be dried with mirabilite, reduced pressure drying, etc.

Furthermore, since impurities such as amorphous substances are not completely removed even by the washing, it is preferable to further purify the acetylated product by passing it through a silica gel column. That is, the acetylated product was dissolved in methylene chloride, toluene, etc., and ethyl acetate/toluene (50011λ/1.5IL) was added.
, developed with acetone/benzene (300 mj2/1.5 J2). Silica gel is Wako Gel C manufactured by Wako Pure Chemical Industries.
-300, 330g, etc. are suitable.

The column effluent is concentrated under reduced pressure and dried under reduced pressure to obtain penta-0-acetylquebrachytol.

Next, the deacetylation operation will be explained.

The penta-0-acetylquebrachytol is hydrolyzed and deacetylated 6. The catalyst used here can be an acid or a base. The acid is preferably hydrochloric acid or sulfuric acid, and the concentration is preferably from IN to 3N, for example, 120 llln of a 2N aqueous hydrochloric acid solution per 35 g of penta-0-acetylquebrachytol. The base is preferably sodium methoxide or an aqueous sodium hydroxide solution; for example, 1 mail of 200 ml of a methanol solution of sodium methoxide is suitable for 35 g of penta-o-acetylquebrachytol.

Further, at this time, it is preferable to add ethyl alcohol, methyl alcohol, etc. as a solvent in an amount approximately equal to that of the acid. This is because the solubility of penta-0-acetylquebrachytol increases.

As for the reaction conditions, it is preferable to heat and reflux the mixture in an oil bath at 100 to 150°C for 10 to 20 hours.

After hydrolysis using an acid, it is preferable to concentrate under reduced pressure again and dry under reduced pressure to obtain a solid. After hydrolysis using a base, the reaction solution is treated with an acidic resin such as Amberlite 1R120.
It is preferable to neutralize with B (imported by Organo), remove the resin, concentrate under reduced pressure, and dry under reduced pressure to form a solid.

Next, L-quebrachitol is isolated and purified. The solid material obtained by deacetylating the solid material using water or the like as a good solvent and ethyl alcohol or the like as a poor solvent is dissolved in a good solvent, and a poor solvent is added thereto until the liquid becomes sufficiently cloudy.

The precipitated crystals are kept at a low temperature for sufficient crystallization, then filtered, washed with ethyl alcohol, n-propyl alcohol, etc., and dried under reduced pressure.

In addition, as confirmation analysis of the obtained L-quebrachytol, 'H-NMR, melting point measurement, and specific rotation measurement were performed, and it was confirmed that highly pure L-quebrachytol could be obtained in high yield. Can be confirmed.

<Examples> The present invention will be specifically described below with reference to Examples.

(Example 1) Natural rubber serum concentrate (solid content 60% by weight) 20011I
1 was placed in an eggplant-shaped flask, water was concentrated under reduced pressure, and the mixture was azeotropically distilled with ethyl alcohol to obtain solid residues of toa and tg.

To acetylate this solid residue, distilled pyridine 2
50ml, suspended in 250mu of acetic anhydride and heated at 60°C for 16
The mixture was heated and stirred for hours. Next, the reaction solution was ice-cooled, 12C1 mJ2 of methyl alcohol was gradually added, and the mixture was stirred at 0°C for 2 hours. This is to decompose the remaining acetic anhydride into methyl acetate and acetic acid to lower the boiling point and facilitate the subsequent vacuum concentration operation. Thereafter, the reaction solution was concentrated under reduced pressure, 1.2jZ of ethyl acetate was added and stirred, and insoluble materials were filtered with suction.

Mother liquor IN-HCl 500a+4! , saturated sodium bicarbonate solution 500
m1, water 500mJZ, saturated sodium chloride aqueous solution 50
After washing twice at 0 mL each time, the organic phase was dried with mirabilite. After filtering the Glauber's salt, the filtrate was concentrated under reduced pressure and further dried under reduced pressure to obtain 40.7 g of an oily residue. This was dissolved in methylene chloride 50o+1, and a column (silica gel, Wakogel C-300, manufactured by Wako Pure Chemical Industries, Ltd., 330g)
and ethyl acetate/toluene (500ml/
1.51).

After development, the column effluent was collected, concentrated under reduced pressure, and further dried under reduced pressure to obtain oily penta-0-acetylquebrachytol (
Penta-o-acetylquebeachito
l) 35.2 g was obtained.

2N to the obtained penta-0-acetylquebrachytol
-120 mj of hydrochloric acid! , and 120 ml of ethyl alcohol were added thereto, and the mixture was heated under reflux in a 110°C oil bath for 16 hours. After cooling, the mixture was concentrated under reduced pressure and further dried under reduced pressure. 30 ml of water was added to the obtained solid, and after dissolving the solid, ethyl alcohol was added until the liquid became cloudy. The amount added was 210 Ilf. Next, the cloudy liquid was left at 7° C. for 48 hours to effect crystallization. The precipitated crystals were suction filtered, washed with ethyl alcohol, and then dried under reduced pressure. The obtained L-quebrachytol crystals were 1
It was 6.5g. The yield was about 15% (by weight) from the solid residue of natural rubber serum.

As confirmation analysis, 'H-NMFt, melting point, and specific rotation were measured for the obtained L-quebrachytol.

'H-NMR is JNM made by JEOL
A GX-400FT spectrometer was used, and heavy water (D2o) was used as the solvent. Moreover, 3-(trimethylsilyl)-1=propanesulfonic acid sodium salt (OSS) was used as an internal standard.

In 'H-NMR analysis, peaks of methine protons having 5 hydroxyl groups, methine protons having methoxy groups, and one singlet peak of 3 protons based on methoxy groups were confirmed with high purity (Figure 1). reference).

Specific optical rotation was measured using a DIP-4 type polarimeter manufactured by JASCO Corporation. The measurement was carried out using a sodium D line and a 10a+m square quartz cell. According to the results of specific rotation analysis, [α] I
)20 = -B Oo (C+H20) was obtained.

Melting points were measured using a MEL-TEMP (US fR) capillary melting point meter. Melting point analysis shows melting point 190-192
It was ℃.

The above values of specific rotation and melting point are the values reported by Anderson (melting point 190-194℃, specific rotation -
81°) and showed good government.

(Report; “THE CARBOHYDRATES”,
Vol, rA, P.

519.1972, W. PigIlan and
D. ) Edited by Iorton, Academic Press
From the above results, the crystals obtained were L-quebrachytol and had high purity.

<Effects of the Invention> The method of the present invention makes it possible to collect a large amount of highly purified L-quebrachytol from natural rubber serum. It can be manufactured and supplied as a food additive, and can be expected to make a major contribution to society.

[Brief explanation of the drawing]

Figure 1 shows 'H-N obtained by one embodiment of the method of the present invention.
It is a graph showing the results of MR.

Claims (2)

[Claims] (1) A method for collecting L-quebrachytol contained in natural rubber serum, which comprises separating and collecting L-quebrachytol contained in natural rubber serum by acetylation treatment. (2) Adding an acetylating agent to natural rubber serum to acetylate L-quebrachytol in the serum, separating the acetylated product using a silica gel column, and then hydrolyzing and deacetylating it. Characteristic method for collecting L-quebrachytol contained in natural rubber serum.