JPH0515716B2 - - Google Patents

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to 2,6-bis(4-hydroxy-3,
Production of 5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, i.e., syringaresinol and its stereoisomers (hereinafter abbreviated as syringaresinols) at a good yield and at low cost. It's about how to do it.

(Prior art) Syringaresinol, which is classified as a lignan, a type of plant component, exists in hardwoods and herbs together with its glycosides, although in small amounts.
It is also known to be contained in lignin, which is one of the major chemical components of hardwoods and herbs. In addition, Acanthopanax senticosus has recently been attracting attention in Japan as being effective in strengthening and enhancing biological defenses, similar to Korean ginseng, which is widely used as a medicinal plant. The existence of lingaresinol and its glycosides has been reported primarily by Soviet scientists. However, although syringaresinol has been attracting attention as a new physiologically active substance, no efficient and economical method for its production has been investigated, and only a few studies have been conducted on plant ingredient chemistry. Only laboratory separation methods have been reported in the research field.

As mentioned above, syringaresinol exists as a glycoside in the extracted components of hardwood wood, and is extracted together with many other components by directly immersing the wood or bark in water-containing methanol. In this case, the amount of syringaresinol extracted is generally extremely small, less than 0.01% of the total wood;
It is about 0.5% in the inner bark of tulipifera, and at most 0.02% in the whole wood. Therefore, there are overwhelmingly many impurities, and the purification of syringaresinol requires a complicated separation process, and the resulting syringaresinol must also be extremely expensive.

In addition, in this method of extracting directly from the wood,
Three types of resinols with extremely similar structures are mixed. That is, in the following formula (), R ₁ = R ₂
In addition to syringaresinol consisting of a syringyl nucleus when = R ₃ = R ₄ = OCH ₃ , R ₁ = R ₃ = OCH ₃ ,
Pinoresinol consisting of a guaiacyl nucleus where R ₂ = R ₄ = H, and R ₁ = R ₂ = R ₃ = OCH ₃ and R ₄ =
In the case of H, medioresinol consisting of both guaiacyl and syringyl nuclei coexists, so it is necessary to perform a more sophisticated separation treatment to isolate pure syringalesinol.

Among herbs, Artemisia
absinthum), periwinkle (Vinca
Syringaresinol has been found in the extracts of plants such as Vinca rosea and Vinca rosea, but in extremely small amounts in both cases.

On the other hand, woody plants and herbaceous plants contain 20-30% and 15%, respectively.
Contains ~25% lignin. Lignin is a monolignol (primary structural unit), parahydroxycinnamyl alcohol, which is dehydrogenated by enzymes in plants to become phenoxy radicals, and the resonance body undergoes radical polymerization to form various dilignols (secondary structural units). It has been clarified that this dilignol is further polymerized to become a polymer in sequence, and finally becomes a polymer substance with a complex three-dimensional network structure.

Typical bond types of dilignols include allylglycerol-α and β-allyl ether, phenylcoumaran, biphenyl, and diallylpropane, and the existence of resinols has also been confirmed, but compared to the former four, The quantity is small. The composition ratio of parahydroxycinnamyl alcohols, which are monolignols, differs depending on the type of plant, so
The types and quantity ratios of dilignors produced are also different. In the following formula (), softwood lignin is
Almost all of coniferyl alcohol when R ₁ = OCH ₃ , R ₂ = H, hardwood lignin, coniferyl alcohol and sinapyl alcohol when R ₁ = R ₂ = OCH ₃ are 1:1, herbaceous Lignin is obtained by adding paracoumaryl alcohol when R ₁ = R ₂ = H and polymerizing each at a composition ratio of approximately 4.5:4.5:1, and syringalesinol is a hardwood containing syringyl units. and is incorporated into macromolecules of herbaceous lignin through ether bonds.

Conventionally, methods for obtaining syringaresinol from these lignins include percolation using hot water [Chem. ，
p464 (1971)], or high-pressure hydrogenolysis using a metal catalyst such as copper-chromium oxide [Mokuzai Gakkai; Vol.19, p165 (1973)]
However, these methods are all separation methods used in the field of research on the chemical structure of lignin, and have little meaning as industrial production methods.

Furthermore, a few laboratory synthesis methods for syringaresinol have been reported, but in any of these methods, it is not easy to obtain a large amount of starting material having a syringyl nucleus, and it is difficult to obtain the final syringaresinol from the starting material. The synthesis steps up to this point are complicated and can be said to be meaningless as an industrial manufacturing method.

(Problems to be Solved by the Invention) The present invention aims to provide a method capable of producing syringaresinols on an industrial scale in place of the conventional production method as described above.

(Means for Solving the Problems) From the perspective of effective use of wood resources, the present inventors have found that lignin and hemicellulose can be used more effectively than the conventional sulfite method or kraft method. In the process of investigating how wood components change through pulping using organic solvents, or organosorvolysis pulping, which is attracting attention, we discovered that when hardwoods and herbs are steamed with hydrous acetic acid, syringaresinol is produced. It was found that these products could be obtained in good yield.

It has already been reported in US Pat. No. 3,553,076 that high-quality pulp consisting of cellulose and a small amount of hemicellulose can be obtained by cooking wood chips in hydrous acetic acid at high temperatures. At the same time, most of the hemicellulose is hydrolyzed into monosaccharides and oligosaccharides, and lignin is decomposed into low-molecular compounds that are easily soluble in organic solvents or alkalis. The present inventors used hardwood wood chips to cook them at high temperature with hydrous acetic acid, separated the insoluble part, that is, the unbleached pulp, and examined the dissolved components of the cooking waste liquid. As a result, they found that syringaresinol. It has become clear that it contains a large amount of , leading to the completion of the present invention.

The present invention involves cooking plants containing lignin having syringyl cores, such as hardwood chips, with hydrous acetic acid at high temperatures, recovering acetic acid from the resulting cooking waste, and then extracting and purifying it with an organic solvent. A novel method for producing syringaresinol is provided, and according to the present invention, syringaresinol can be economically and efficiently produced in good yield from inexpensive and easily available raw materials. I can do it.

The process for producing syringaresinol of the present invention consists of a process of cooking a raw material plant with hydrous acetic acid, and a process of extracting and purifying the cooking waste liquid with an organic solvent, and these steps will be explained in detail below.

The raw material plants used in the present invention include broad-leaved trees,
Any material that contains lignin with a syringyl core, such as bamboo, straw, cottonseed husks, coconut husks, and almond husks, can be used, but if the content is low, there will be a lot of impurities, making the purification process complicated. Therefore, since this is economically disadvantageous, it is preferable that Klason lignin contains 5% or more of the plant body. In addition, considering workability and cooking efficiency, the shape of the raw material is preferably chips or small pieces of several centimeters or less.

The above-mentioned plant body is placed in a pressure vessel, and acetic acid containing water is added as a cooking liquid and sealed. As cooking liquid,
If the water content increases, the solubility of the lignin decomposition product will decrease, and the elution of lignin from the plant will be suppressed, resulting in a low yield. Especially good. Additionally, a suitable lignin solvent other than acetic acid may be added to the cooking liquor;
Specific examples include methanol, ethanol, propanol, isopropanol, acetone, dioxane ethyl acetate, etc. However, if the amount of these additive solvents is too large, the reaction to lower the molecular weight of lignin will be suppressed, and the yield of syringaresinols will be reduced. The rate is low and it is not appropriate.

In addition, the ratio of cooking liquor to raw material plant varies depending on the type of raw material plant, but usually 3 or more is required.
If it is less than 3, the reaction to lower the molecular weight of lignin and the elution of decomposed products tend to be insufficient.

The optimum treatment temperature is 150-200°C. At temperatures below 150°C, the reaction to reduce the molecular weight of lignin is insufficient.
The production of syringaresinol is also small. or,
The higher the temperature, the faster the reaction progresses, and the yield of syringaresinol tends to be higher. However, when the temperature exceeds 200℃, the lignin, which has been reduced to a low molecular weight, undergoes a condensation reaction, resulting in complex formation due to carbon-carbon bonds. This results in a condensation product, and the yield of syringaresinol becomes low.

The maximum temperature holding time varies depending on the type of raw material plant, but it is usually between 30 minutes and 10 hours; longer treatment will lower the yield of syringaresinol and is not economically viable. It is disadvantageous.

Through the above treatment, the hemicellulose in the raw material plant is hydrolyzed and becomes soluble in the acetic acid solution, the lignin is also reduced in molecular weight, and the lignin decomposition products containing syringaresinols are dissolved in the acetic acid solution.

Next, the digested plant is removed from the pressure vessel and dissolved components and residue are separated. A filter or centrifugal dehydrator or the like is used for separation. Since the separated residue has adsorbed dissolved components, it is redispersed in fresh acetic acid solution to extract the dissolved components. Both solutions are combined, the solvent is distilled off, and the mixture is concentrated. This concentrate is a mixture of a water-soluble hemicellulose hydrolyzate and a water-insoluble lignin decomposition product containing syringaresinol, which is directly separated and separated by a known method.
Although it may be purified, syringaresinol can be obtained more efficiently by separating and removing the water-soluble portion in advance.

When the above concentrate is added dropwise to 5 to 10 times the volume of water with stirring, the lignin decomposition product containing syringaresinols precipitates, and the hemicellulose hydrolyzate dissolves in the water. The precipitate is collected by centrifugation or filtration and then dried to obtain a dark brown solid containing syringaresinol. This product may be purified by a known method, but since it contains many impurities and its purity is low, it is further dissolved in ether, ester, aromatic hydrocarbon, or chlorinated hydrocarbon, and the soluble portion is collected. It is more efficient to purify the target product with high purity.

Alternatively, the cooking eluate may be freeze-dried or dried under reduced pressure to remove water, and then extracted with ether, ester, aromatic hydrocarbon, or chlorine-substituted hydrocarbon. When the solvent is distilled off from the extract, a solid containing 5 to 10% of lingaresinol is obtained. The yield of this solid material varies depending on the type of raw material plant, but for hardwoods, the yield is 10 to 10% per dry weight.
reaching 15%.

If the obtained solid is purified according to known methods such as recrystallization or various chromatography, highly pure syringaresinol can be obtained.
The syringaresinol obtained in the present invention is syringaresinol and epicyringaresinol,
Both are optically inactive.

(Function) According to the present invention, a much larger amount of syringaresinol can be obtained than the amount originally present in the lignin and extracted components of the raw material plant. The detailed mechanism of its formation will have to wait for future research including model experiments, but it can be thought of as follows.

Due to the catalytic action of high-temperature acetic acid, lignin in plants cleaves allylglycerol-α and β-allyl ether, which are the most important bonds in lignin, and sequentially becomes lower molecular weight. By removing one molecule of water from the syringylglycerol-β-allyl ether bond shown, a quinone methide structure of the following formula () is formed, and then the β-allyl ether bond is radically cleaved to form the following: A quinone methide radical of formula () is generated. After these two molecules of quinone methide radical are recoupled, a ring is formed to produce syringaresinol. The produced syringaresinol has a stable side chain structure, and the aromatic ring is also stable because the ortho and para positions of the phenolic hydroxyl group are occupied, and the only reactive position is the phenolic hydroxyl group, producing phenyl ether. Even if it does, it is thought that it will immediately cleave and return to the original syringaresinol.

The present inventors have demonstrated by nuclear magnetic resonance spectra that allylglycerol-β-allyl ether bonds have almost disappeared in the lignin decomposition product obtained by cooking hardwood under the conditions of the present invention. This has been confirmed by

In addition, in in vitro enzymatic dehydrogenation polymerization or dehydrogenation polymerization using an oxidizing agent, which is a typical radical reaction of sinapyl alcohol, syringaresinol is usually converted to 70% via quinone methide radical. It has also been revealed that it is produced with a yield of ~90% [Wood Research; No. 61, p44
−53 (1976)].

Therefore, under the conditions of the present invention, the quinone methide radical of the above formula () is generated by the cleavage of the syringyl glycerol-β-allyl ether bond in the lignin containing the syringyl nucleus, and the quinone methide radical once generated is It is thought that the syringaresinol is re-condensed, resulting in the production of a large amount of syringaresinol. Furthermore, according to these conditions, the entire reaction system is strongly acidic, so that syringaresinol is easily converted into episyringaresinol.
Therefore, it is considered that the episyringaresinol obtained in the present invention is produced by changing the syringoresinol produced by the mechanism described above.

(Effects of the Invention) According to the present invention, syringaresinols can be produced at extremely high yields using readily available and inexpensive plants such as hardwood, bamboo, and coconut shells as raw materials. Moreover, since neither the process of digesting the plant body nor the process of extraction using an organic solvent requires complicated manufacturing equipment or processing operations, industrialization is easy. You can expect high profits as it can be obtained as

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

[Example 1] 5 birch wood chips with a dry weight of 700 g
Place in autoclave, acetic acid concentration 95%, liquid ratio 5
Add acetic acid and water and encapsulate. After heating with a gas burner and raising it to 175℃ in 30 minutes,
It was kept at 173-177°C for 2.5 hours. Thereafter, it was rapidly cooled, the contents were taken out, and the pulp and solution were separated by suction filtration. Pulp another 20 95
% acetic acid, defibrated and washed while stirring. Thereafter, the pulp is separated, and this liquid and the liquid are combined and concentrated.

When a solution concentrated to about 50% is added dropwise to 3.5 liters of water with stirring, a brown precipitate forms. The precipitate was collected by centrifugation and dried to obtain 156 g of a dark brown solid containing syringaresinol.
This solid was mixed with dichloroethane:ethanol/2:
When it is dissolved in a mixed solution of 1 (volume ratio) and added dropwise to isopropyl ether of 15, a light brown precipitate is formed, and the isopropyl ether solution becomes light reddish brown. The precipitate was separated by centrifugation, and the isopropyl ether solution was concentrated and dried to obtain 33 g of a solid containing syringaresinol.

This solid was charged to a column packed with 500 g of Wakogel C-200, eluted with benzene:ethyl acetate/3:1 as a developing solvent, and while monitoring with silica gel thin layer chromatography, The portion containing resinol and epicillin galesinol was collected. A portion consisting only of syringaresinol and episyringaresinol, and a portion containing a mixture of both were obtained. The mixed portion was eluted again using a column filled with 100 g of Wakogel C-200 under the same conditions as above, and separated into syringaresinol and episyringaresinol portions. Each was combined with the portion obtained above and recrystallized from dichloromethane-n-hexane to obtain 1.8 g and 2.1 g of pure crystals of syringaresinol and episyringaresinol, respectively.

The infrared absorption spectra of the obtained syringaresinol and episyringaresinol crystals completely matched the infrared absorption spectra of their respective standard products.
Also, no decrease in melting point was observed in the mixing test.

[Example 2] Beech wood chips weighing 700 g (dry weight) were placed in an autoclave, and acetic acid and water were added so that the liquid ratio was 6 and the acetic acid concentration was 75%. Heat to 3°C and 178-182°C
After holding for a period of time, it was quickly cooled and the pulp and liquid were separated according to the procedure of Example 1. The separated liquid was concentrated and reprecipitated in water in the same manner as in Example 1, and the precipitate was dried to form a brown solid.
Obtained 152g. After pulverizing this solid material, it was added to a 1.5 acetone solution and stirred to dissolve it. After stirring for 2 hours, insoluble portions are separated and removed by centrifugation to obtain an acetone solution. Add this acetone solution to 15
The resulting precipitate was removed by centrifugation again, and the ethyl ether solution was concentrated and dried to obtain 31 g of a brown solid containing the desired syringaresinol.

This solid was subjected to column chromatography under the same conditions and procedures as in Example 1 to obtain syringaresinol and episyringaresinol parts, which were recrystallized from methanol-chloroform to obtain pure syringaresinol. 1.5 g and 1.9 g of crystals of resinol and epicillin galesinol were obtained, respectively. The infrared absorption spectra of the obtained crystals of syringaresinol and episyringaresinol completely matched the infrared absorption spectra of the respective samples, and no drop in the melting point was observed in the mixing test.

[Example 3] Cotton seed husks weighing 700 g as a dry weight were prepared at a liquid ratio of 6.5, acetic acid concentration of 85%, a maximum temperature of 165°C, and a maximum temperature holding time of 4.
Cooking, filtration, and concentration were carried out according to the equipment and procedure of Example 1 under the following conditions, and the concentrated liquid was dropped into water.
130 g of water-insoluble portion was obtained. The obtained water-insoluble portion was dissolved in a dichloroethane-ethanol solution in the same manner as in Example 1, and the solution was added dropwise to isopropyl ether to obtain 25 g of isopropyl ether-soluble portion. This isopropyl ether soluble portion was treated under the same conditions and procedures as in Example 1 to obtain 0.7 g of syringaresinol and 0.9 g of episyringaresinol crystals.

Claims (1)

[Scope of Claims] 1. A plant body containing lignin having a syringyl core as a component is digested with a hydrous acetic acid solution, and a water-insoluble part in the cooking liquor obtained is extracted with an organic solvent. 2. , 6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane. 2. 2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7 according to claim 1, characterized in that a woody broad-leaved tree or a herbaceous plant is used as the plant. -Production method of dioxabicyclo[3.3.0]octane. 3. 2,6-bis(4-hydroxy-3,5-
Method for producing dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane. 4 Alcohols, ethers,
2,6-bis(4-hydroxy-3,5-dimethoxyph) according to claim 1, characterized in that ketones, esters, chlorine-substituted hydrocarbons or aromatic hydrocarbons are used. enyl)-3,7
-Production method of dioxabicyclo[3.3.0]octane. 5. 2,6- according to claim 1, wherein the hydrated acetic acid solution contains less than 50% by weight of water.
A method for producing bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane. 6. 2,6-bis(4
-Hydroxy-3,5-dimethoxyphenyl)-
Method for producing 3,7-dioxabicyclo[3.3.0]octane.