JPS62292785A - Separation and purification of syringaresinols - Google Patents

Abstract

PURPOSE:To advantageously and industrially obtain the titled compound useful for a roborant, etc., by pulverizing or digesting a plant body containing lignin having syringul nucleus by a specific method, then extracting with an alkali aqueous solution and subjecting the resulting extraction liquid to adsorption with an adsorbing resin, followed by elution. CONSTITUTION:A plant body containing lignin having syringyl nucleus as an ingredient is heated under pressure in a pressure vessel in a hydrous state and rapidly discharged into a receiver tank in normal pressure to be pulverized or digested by a water-containing acetic acid in the pressure vessel, and then a water-insoluble part in the pulverized material or digested liquid of this plant body is extracted with an alkaline aqueous solution. Then an adsorbing resin in brought into contact with this extraction liquid to adsorb, and eluted with a water-soluble organic solvent to remove a water-soluble part from the eluate to give 2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3-.0]octane.

Description

Detailed Description of the Invention 3. Detailed Description of the Invention (Field of Industrial Application) The present invention relates to 2,6-bis(4-hydroxy-6°5-dimethoxyphenyl)-3,7-thioxabicyclo( 3,3
, 0] octane, that is, syringaresinol and its stereoisomers (hereinafter abbreviated as syringaresinols), in a high yield and at low cost.

(Prior art) Syringaresinol, which is classified as a lignan, which is a type of plant component, exists in hardwoods and herbs together with its glycosides, although in small amounts. It is known that metal is contained in lignin, which is one of the main chemical components of this type of metal. Also, recently in our country, Eleuthero (
Acantho-panax 5ent+cnsu
Similar to Korean ginseng, which is widely used as a medicinal plant, s) has attracted attention as being effective in tonicizing and enhancing biological defenses, but syringaresinol and its glycosides are active ingredients in Eleuthero. The existence is mainly
It was reported that it was created by a Soviet scientist. However, although syringaresinol has been attracting attention as a new physiologically active substance, no efficient and economical method for its production has been explored, Only laboratory separation methods in the research field of component chemistry had been reported.

The present inventors have previously proposed a new production method that allows syringaresinol to be obtained in good yield from inexpensive and easily available raw materials. That is, on the one hand, a plant body containing lignin containing syringyl cores, such as hardwood chips, is sealed in a pressure vessel, subjected to pressure and heat treatment in a water-containing state, drawn, lowered, and rapidly discharged into a receiving tank under normal pressure. Then, the water conservancy chips are subjected to a so-called blasting process of pulverizing them into fine particles, and then extracted with an organic solvent such as methanol, separated,
This is a purification method (Japanese Patent Application No. 11B60-58079). On the other hand, after cooking hardwood chips with hydrous acetic acid,
This method involves extracting, disintegrating, separating, and purifying the seedlings using a total organic solvent in the cooking reaction solution.

In these methods, syringylglycerol-α and β-allyl ether bonds in lignin are cleaved during blasting and cooking, and a large amount of syringaresinol is then involved in the production and polymerization of quinone methide-type radicals. This is an innovative manufacturing method.

It can be said that these methods have made it possible for the first time to industrially produce syringaresinols.

(Problems to be Solved by the Invention) However, even when the above production method is adopted, as long as extraction, separation, and purification steps 8 are performed using conventional methods, large amounts of organic solvents are used, However, there are still unresolved problems such as complicated operation.

The present invention aims to provide a method for efficiently separating and purifying phosphorus resinols produced by an explosion method and an acetic acid digestion method.

(Means for solving the problem) The uninvented names aim to establish a more efficient and economical method for producing syringaresinol by the above-mentioned blasting method and hydrous acetic acid digestion method. As a result of our research, we found that the syringaresinol portion was extracted with an alkaline aqueous solution as a method for separating and purifying it after the organic electrolyte extraction following the blasting treatment or acetic acid digestion treatment.
After treating L with an adsorption resin, it is eluted with a water-soluble organic solvent, and the water-soluble portion is extracted and removed from the eluate. They discovered that syringaresinol could be economically advantageously separated and purified after 5 years of operation, and completed the present invention. A step in which the syringaresinol produced by the blasting method or acetic acid digestion method is extracted with an alkaline aqueous solution, the extract is treated with an adsorption resin to adsorb the target product, and then eluted with a water-soluble organic solvent. The process consists of a step of extracting and removing the water-soluble part from the concentrate of the eluate and condensing the syringaresinol, and a step of purifying the concentrated part of the syringaresinol. The process will be explained in detail. The raw material plant used in the present invention is a broad-leaved tree.

Any material containing lignin having a syringyl core as a component, such as bamboo, straw, coconut shell, coconut shell, or almond shell, can be used. In addition, in consideration of workability and processing efficiency, the shape of the raw material is preferably a number of pieces or smaller pieces.

In the case of blasting, the above-mentioned plant body is treated with 15-30 kg/- of superheated steam for 5-30 minutes, and the resulting fine powdered hydrated plant body is added to an alkaline aqueous solution such as Na0)i, KOH, etc. as it is or After being suspended in several times the amount of water and filtered, it is immersed to extract syringaresinol along with the lignin decomposition product. In this case, if water extraction is performed in advance, organic acids such as acetic acid and xylic acid will be removed together with sugars and sugar-modified products, and in addition to the alkali necessary for extraction, the organic acids will be consumed to neutralize these organic acids. This is advantageous in that not only can alkali be saved, but also contamination and deterioration of the resin in the subsequent resin adsorption step can be reduced.

In addition, in the case of acetic acid digestion, the above-mentioned plants are treated with an acetic acid solution containing less than 50% water at 150-200°C for 1-5 hours, and the cooking reaction solution containing syringaresinols is reduced by 10%, and then water is added. The resulting insoluble portion is extracted and dissolved in the aqueous alkali solution.

By this alkali treatment, the lignin decomposition products having free phenolic hydroxyl groups, including syringaresinols, are converted into water-soluble alkali salts and extracted.

A suitable alkali for extracting syringaresinols is an alkali metal hydroxide. The concentration used can be diluted, but if the pH is below 10, a large amount of alkaline solution is required, the extraction efficiency is low, and the yield of syringaresinol is low.

Additionally, if the concentration of the alkaline solution is extremely high, it will be necessary to adjust the pH of the extract in order to prevent deterioration of the adsorption resin in the subsequent resin process, which will require the use of a large amount of acid, making the process complicated. Therefore, it is economically disadvantageous. Therefore,
The appropriate concentration of the alkaline solution used is 0.1 to 10%, but if the pH is adjusted to within the range of 10 to 14 at the final stage of extraction, it can be sent directly to the subsequent resin process, making it more efficient. It is.

The extract of the lignin decomposition product containing syringaresinols extracted with alkali under stirring is separated from the residual plant body or insoluble portion by filtration or centrifugation. This extract contains macromolecules with a molecular weight of several thousand to small molecules with a molecular weight of about 100.

If the pH of this extract exceeds 14, it is adjusted to 14 or less and then passed through a column filled with an adsorption resin made of a copolymer of styrene and divinylbenzene together with water. The part consisting mainly of low-molecular decomposition products, including syringaresinol, is adsorbed by the resin, while the high-molecular part passes through the column without being adsorbed. in this case,
The rate at which the liquid is passed through the column varies depending on the processing conditions and extraction conditions of the raw material plant, but the rate at which the hardwood material is passed through the column is 25 to 30 kg/
When the material is blasted under pressure for 10 minutes, extracted with hot water, and then extracted with a 1% NaOH aqueous solution with a volume of 20 times the weight of the material, the volume is less than 10 times the filling volume of the resin. However, it is not appropriate to pass the liquid at a rate of 20 times or more because there is a possibility that some of the syringaresinol may pass through without being adsorbed. After finishing the liquid passage, the resin is washed with water about 3 to 5 times the amount of resin.

The adsorption resin used in the present invention is a copolymer with a giant network structure, and a copolymer of styrene and divinylbenzene is well known.
2 (product name) and Mitsubishi Kasei Corporation's Iaion) lP20
(trade name) 0 Next, in order to elute the syringaresinol adsorbed on the resin, a water-soluble organic solvent such as methanol or acetone is passed through the column. The appropriate rate of liquid flow is 5 times or less the filling volume of the resin per hour. If the liquid is passed 10 times or more, the replacement of the solvent with the adsorbed material on the resin will be insufficient, and a large amount of elution solvent will be required to completely remove the syringaresinol, which will reduce efficiency. Not the point. The total amount of liquid to be passed through requires approximately 2 to 5 times the volume of the filled resin. After the elution operation is completed, water is allowed to pass through and the bathing solvent is replaced, thereby regenerating the resin.

The eluate is concentrated and the solvent is distilled off to obtain a brown solid containing syringaresinols. The amount of solids obtained is approximately 174 in the solid content of the extract passed through the resin under the above-mentioned crushing treatment conditions, and the amount of syringaresinol is approximately 4.
Concentrated twice as much. Moreover, most of this solid material is a water-soluble alkali salt, but syringaresinol is not an alkali salt, but is free syringaresinol itself. Therefore, it is not necessary to treat this portion with an acid or the like to liberate it, and pure syringaresinol can be obtained by directly purifying it by a method such as column chromatography. However, as it is, there are many impurities, and when it is subjected to column chromatography, etc., a large amount of carrier and solvent is present, so after removing water-soluble parts such as alkali salts, It is better to make it by IT. To remove the water-soluble portion, suspend the solid in water, stir well, and then collect the insoluble portion, or suspend the solid in an organic solvent that is poorly soluble in water, such as chloroform, stir well, and then collect the insoluble portion. There are two methods: collecting the dissolved part, adding water, shaking and washing, and distributing it using a liquid-liquid system such as water-ethyl acetate. By these methods, the content of syringaresinol in the solid material obtained after removing the water-soluble part was 10
~40%. If this concentrated Claxin is produced by various methods such as chromatography, pure crystals of syringaresinol can be efficiently obtained.

The syringaresinol obtained in the present invention is syringaresinol and evisyringaresinol, both of which are optically inactive.

(Example) Hereinafter, the present invention will be specifically explained based on Examples.

[Example 1] A pressure vessel (withstand pressure 40 kg/ctA, container 21), which had a steam blowing pipe and an air discharge pipe in the upper part, a discharge pipe with a ball valve in the lower part, and a receiver tank with a silencer, was made of birch wood. 200 g of the chip was sealed as a dry product. Then open the air exhaust pipe and pump 2 kg for 2-3 seconds at a time.
/-gauge of saturated steam was blown in to expel the air, and this operation was repeated six times. After steam replacement, the air exhaust pipe was closed, and 30 kg/-gauge saturated steam was introduced into the pressure vessel and jacket to rapidly heat and pressurize. The maximum temperature reached in the container was 265°C. After reaching 235℃,
Immediately, the introduction of saturated steam was stopped, and this state was maintained for 8 minutes. After that, the lower pole pulp is opened and the contents of the pressure vessel are discharged into the receiving tank within a very short time. The ejection time is almost instantaneous.

The inside of the receiving tank was washed with water, and the discharged birch fine powder was collected as a suspension.

Add hot water of about 80°C to the obtained fine powder suspension and prepare 1 of 21.
The mixture was dispersed in an aqueous solution of NaQH, stirred, and then filtered. The same treatment was repeated two more times, and a total of six alkaline extracts were combined. The pH of this alkaline extract was 11.8, and the solid content was 77 g.

This alkaline extract was added to Amberlite X manufactured by Organo.
3/hour to a column packed with 1/i water of AD-2.
The liquid was passed at a rate of 1. After passing the alkaline extract, 51 parts of water was passed at a rate of 31 parts per hour to wash the resin. The combined solid content of the passing liquid and washing liquid was 56 g.

Next, 3j of methanol was passed through at a rate of 1.5j per hour, and the eluate was collected. When the obtained eluate is concentrated to dryness, 2
1.5 g of solid was obtained. This solid was pulverized, dispersed in 400 mj of water, and then extracted with 100 mj of ethyl acetate. Ethyl acetate extraction was performed three times, with a total extracted solid of 5.5 g.

This solid was charged into a column packed with silica gel (Nie 200 manufactured by Wako), and ethyl acetate:benzene/1:
3 (volume ratio), and the shrimp syringaresinol and syringaresinol portions were collected while monitoring by silica gel thin layer chromatography.

A portion consisting only of shrimp syringaresinol and syringaresinol, and a mixed portion of both are considered. The mixed part is the same
Silica gel column chromatography was performed again under the same conditions to obtain 1.7 g and 1.2 g of crude crystals of syringal and galesinol, respectively.

When each crude crystal was recrystallized with dichloromethane-n-hexane, 1.6 g and 1.0 g of pure crystals of evicilingaresinol and syringaresinol were obtained, respectively, and the infrared absorption spectra of each standard were obtained. and the melting points were the same. Also, in the mixing test with each standard sample, no melting point depression of 1 was observed.

[Example 2] The number of cotton seeds of 200 g as dry weight was used in saturated water vapor of 2
5 kg/c! Ii gauge, maximum temperature approximately 220℃.

The apparatus of Example 1 under the conditions of Itsukushima temperature holding time of 12 minutes.

Follow the procedure to obtain a fine powder suspension.

The obtained fine powder suspension was subjected to hot water extraction treatment in the same manner as in Example 1, and the filtration residue was extracted under the same conditions as in Example 1.
Step 5: Extraction with an aqueous NaQH solution. The pH of the obtained extract was 11.6. This extract was passed through a column filled with 1j of Yuyaion HP 20 manufactured by Mitsubishi Kasei Co., Ltd. together with water under the same conditions as in Example 1, and further,
After washing with water, it was eluted with ethanol. Ethanol was distilled off from the eluate and dried to obtain 26 g of solid.

This solid was crushed, dichloromethane soomz was added, and the mixture was stirred and extracted for 6 hours. After that, centrifugation was performed to remove the residue, and 100ml of water was added to the resulting dichloromethane solution.
/ was added, shaken and washed, the solvent was distilled off from this dichloromethane solution, and the residue was subjected to silica gel column chromatography under the same conditions as in Example 1 to separate the syringaresinol and evisyringaresinol parts. A good friend. Recrystallization was performed with dichloromethane-n-hexane to obtain pure syringaresinol and 1,0Ji ('j) crystals of pure syringaresinol and evisyringaresinol, respectively. The infrared absorption spectrum and melting point of Garesinol matched those of each sample, and no decrease in melting point was observed in the mixing test with each sample.

[Example 6] Beech wood chips with a dry weight of 70'Og were placed in a 51 autoclave, and the liquid ratio was 6. Acetic acid and water were added and sealed so that the acetic acid concentration was 90%. 180℃ in the first 30 minutes
The mixture was heated to 178 to 182°C for 6 hours, and then quickly cooled. Thereafter, the contents were taken out and the pulp and liquid were separated by filtration. The residue was immersed in 90% acetic acid of No. 51 and disintegrated using a mixer, and then the liquid and bulb were separated by filtration again and concentrated together with the P liquid. Approximately 1.
After concentrating to 51 ml, it was added dropwise to 151 ml of water, and the resulting precipitate was centrifuged and collected. After washing the collected precipitate with water, 1% NaOH9/ was added to the precipitate to dissolve it. The pH of the alkaline solution was 12.3.

As in Example 1, this alkaline solution was filled together with 6E gold water of Amberlite XAD-2 manufactured by Olga 7 Co., Ltd., and passed through the column at a rate of 3j/hour, followed by elution. The solvent was distilled off from the methanol eluate obtained, and when dried, 61 g
A solid substance was obtained.

This solid was dispersed in water according to the procedure of Example 1, and then extracted with ethyl acetate. The ethyl acetate extract was subjected to silica gel column chromatography under the same conditions and procedures as in Example 1, and then recrystallized from dichloromethane n-hexane to obtain pure syringaresinol and Ebishiri/
2.8g and 3.1g of Garesinol crystals respectively. It was confirmed that each of the obtained crystals was syringaresinol and ebisyringaresinol by comparison with standard products. ,
Using readily available and inexpensive plants such as bamboo and coconut shells as raw materials, syringaresinol gold can be produced at an extremely high yield, and then efficiently separated and purified. Moreover,
Neither the process of extracting and dissolving with alkali nor the process of treating with resin requires complicated processing equipment or operations, so industrialization is easy and high economic efficiency can be expected.

Claims (5)

[Claims] (1) A plant body containing lignin having a syringyl core as a component is (a) pressurized and heat-treated in a water-containing state in a pressure vessel, and then rapidly discharged into a receiving tank under normal pressure and pulverized;
or (b) after being digested with hydrous acetic acid in a pressure vessel;
The water-insoluble part in the crushed product or cooking liquor of the plant is extracted with an alkaline aqueous solution, the extract is adsorbed with an adsorption resin, and the water-soluble part is removed from the eluate by elution with a water-soluble organic solvent. 2,6-bis(
4-hydroxy-3,5-dimethoxyphenyl)-3,
Separation of 7-dioxabicyclo[3,3,0]octane
Purification method. (2) 2,6-bis(2,6-bis(
4-hydroxy-3,5-dimethoxyphenyl)-3,
Separation of 7-dioxabicyclo[3,3,0]octane
Purification method. (3) 2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7 according to claim 2, wherein the alkaline aqueous solution is an aqueous solution of an alkali metal hydroxide. - Separation and purification method of dioxabicyclo[3,3,0]octane. (4) Claim 1, characterized in that a copolymer of styrene and divinylbenzene is used as the adsorption resin.
2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3,3
, 0] Octane separation and purification method. (5) 2,6-bis(4-hydroxy- 3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3,3,0
] Octane separation and purification method.