JPS5812280B2 - Method for producing cyclobranol or its organic acid ester - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to an improved method for producing cyclobranol or its organic acid ester by isomerizing 24-methylenecycloartanol or its organic acid ester.

More specifically, the present invention relates to a method for isomerizing 24-methylenecycloartanol or its organic acid ester into cyclobranol or its organic acid ester in high yield without causing side reactions.

Oryzanol, whose main ingredient is cyclobranol ferulic acid ester, which is a type of organic acid ester of cyclobranol, acts on the diencephalic hypothalamus and limbic system, and is useful for the treatment of autonomic nervous system imbalance and menopausal disorders. It is known to be effective and is also used as a treatment for chronic gastritis, irritable bowel disease, and peptic ulcers.

Until now, as a method for producing cyclobranol or its organic acid ester, a method has been known in which 24-methylenecycloalknol or its organic acid ester is heated to a relatively low temperature of less than 100°C in the presence of an acidic catalyst. (Tokuko Showa 5
1-39218, Japanese Patent Publication No. 51-40077).

However, this method has a low yield of about 40-46% because a part of the raw material compound and a part of the coexisting cycloartenol or its organic acid ester are decomposed or altered.
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On the other hand, a method for obtaining cyclobranol by treating oryzanol in a nonpolar linear hydrocarbon solvent in the presence of activated clay is also known.

However, in this method, the rearrangement reaction from 24-methylenecycloartanol to cyclobranol involves an increase in the amount of sterols such as stigmasterol and β-sitosterol, and a considerable decrease in the amount of cycloartenol. This inevitably results in a decrease in overall yield.

The present inventor has conducted intensive research to overcome the drawbacks of such conventional methods and to develop a method for producing cyclobranol or its organic acid ester in high yield. If the organic acid ester is reacted in an anhydrous organic solvent with sodium alcoholate or potassium alcoholate as a catalyst, isomerism can be smoothly achieved even at high temperatures of 100°C or higher without causing undesirable side reactions such as alteration or decomposition. It was discovered that cyclobranol or its organic acid ester could be obtained in high yield as the reaction progressed, and the present invention was completed based on this finding.

That is, in the present invention, when 24-methylenecycloartanol or its organic acid ester is isomerized to produce cyclobranol or its organic acid ester, the raw material compound is mixed with sodium alcoholate or potassium alcoholate in an anhydrous organic solvent. The present invention provides a method for producing cyclobranol or an organic acid ester thereof, which comprises heating to a temperature in the range of 100 to 160°C in the presence of cyclobranol or an organic acid ester thereof.

24-methylenecycloartanol or an organic acid ester thereof is used as a raw material compound in the method of the present invention. In the case of an organic acid ester, if a free carboxyl group is present, this acts on the sodium alcoholate or potassium alcoholate, resulting in an undesirable effect. Since the organic acid is activated, it is necessary to use an organic acid in which all carboxyl groups have been esterified.

That is, when an organic acid has two or more free carboxyl groups, all of the free carboxyl groups therein are 24
- It is necessary that the polyvalent ester be in a form that is used for bonding with methylenecycloartanol.

Organic acids used to form esters of 24-methylenecycloartanol include, for example, formic acid, acetic acid, impropionic acid, butyric acid, isobutyric acid, valeric acid,
Aliphatic monocarboxylic acids such as invaleric acid, methyl ethyl acetate, trimethyl acetate, caproic acid, caprylic acid, pelargonic acid, cabric acid, palmitic acid, stearic acid, malonic acid, succinic acid, curtaric acid, methylsuccinate, ethyl Aliphatic dicarboxylic acids such as malonic acid, dimethylmalonic acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebannic acid, or these with 1 to 1 carbon atoms
Monoesters with 6 alcohols, glycols, α
- fatty acid oxycarboxylic acids such as oxypropionic acid, β-oxypropionic acid, oxymalonic acid, mesoxalic acid, malic acid, tartaric acid, itartaric acid, oxyparaconic acid (itartrate lactone), citric acid, incitric acid, alloisocitric acid or mono- or diesters of these with alcohols having 1 to 6 carbon atoms, aliphatic ketocarboxylic acids such as pyruvic acid, acetoacetic acid, acetone dicarboxylic acid, α-ketoglutaric acid, and levulinic acid, or these mono- or diesters with alcohols having 1 to 6 carbon atoms; Examples include mono- or diesters with alcohol.

In particular, as aliphatic organic acids, saturated compounds are generally preferred over unsaturated compounds.

In addition, benzoic acid, methylbenzoic acid, ethylbenzoic acid, oxybenzoic acids (such as salsic acid, methoxybenzoic acid, and ethoxybenzoic acid), dioxybenzoic acids (
For example, glotocatechuic acid, vanillic acid, invaranilic acid, baellatrum acid, piperonyl acid, etc.), trioxybenzoic acids (for example, gallic acid, etc.), benzenedicarboxylic acids (for example, phthalic acid, inphthalic acid, terephthalic acid, or these having 1 to 10 carbon atoms) monoesters with aliphatic or aromatic alcohols), benzenetricarboxylic acids (
For example, trimesic acid, trimellitic acid, hemimellitic acid or mono- or diethyl acids thereof with aliphatic or aromatic alcohols having 1 to 10 carbon atoms (7-A/), carboxylic acids having a benzene ring (e.g. phenyl acetic acid, aromatic mono-, di- or tri-carboxylic acids such as hydroatropic acid, hydrocinnamic acid, cinnamic acid, allocinnamic acid, coumaric acid, mandelic acid, ferulic acid, benzoyl acetic acid, etc.) or derivatives thereof and cyclopropanecarboxylic acid; Alicyclic carboxylic acids such as cyclopenecarboxylic acid, naphthenic acid, naphthalic acid, quinic acid or monoesters thereof can also be used.

These raw material compounds used in the method of the present invention do not necessarily have to be in pure form; for example, a mixture of 24-methylenecycloartanol and one or more types of 24-methylenecycloartanol organic acid ester, 24-methylenecycloartanol, etc. A mixture of at least two or more types of cycloartanol organic acid esters, at least one or more types of 24-methylenecycloartanol and 24-methylenecycloartanol organic acid esters, and other sterols (or sterine), triterpene alcohols, sterol organic 1 of acid ester or triterpene alcohol organic acid ester
oryzanol containing at least one of 24-methylenecycloartanol and 24-methylenecycloartanol ferulate ester, 24-methylenecycloartanol and 24-methylenecycloartanol ferulate ester; It may also be in the form of a mixture of oils and fats.

Originally, vegetable oils such as rice bran oil, rice bran germ oil, wheat germ oil, peanut oil, sesame oil, corn oil, and olive oil contain
Oryzanol contains 24-methylenecycloartanol ferulic acid ester as an active ingredient, and commercially available oryzanol is mainly manufactured using these vegetable oils as raw materials, but various oryzanol-containing products obtained during this manufacturing process can also be used as a raw material in the method of the present invention.

For example, in the deacidification process of vegetable oil, that is, for the purpose of refining vegetable oil to obtain edible neutral oil, the free fatty acids in the raw vegetable oil are centrifuged as alkaline soap.The crude oil and fat containing a large amount of alkaline soap is called "futsu". The crude fatty acid obtained by treating these foods with inorganic acids such as sulfuric acid and hydrochloric acid is called dark oil, but since oryzanol has the property of being well soluble in alkaline fats and oils, it is used as a byproduct during the deoxidation process of vegetable oil. In the obtained futz and dark oil, oryzanol is transferred from the feedstock oil and concentrated, resulting in a concentration of about 3% compared to the original price oil.
It is concentrated to ~15 times its volume and contains about 1 to 30% oryzanol.

In addition, the residual concentrate obtained by separating the fatty acids in the dark vegetable oil by distillation, or the residual concentrate obtained by esterifying the fatty acids in the dark vegetable oil with a lower alcohol and then separating it by distillation, or the vegetable oil, can be treated with an ion exchange resin. The resulting oryzanol-containing oil contains 2 to 70% oryzanol.

Furthermore, the water-containing solvent is separated from the solution of the oryzanol-containing polar solvent obtained by alkaline deoxidation treatment of vegetable oil in the presence of a water-containing polar solvent (e.g., 50% ethanol aqueous solution) and a non-polar solvent (e.g., hexane). The concentrate contains 30-70% oryzanol.

All of these oryzanol-containing materials are suitable as raw materials for the method of the present invention.

It goes without saying that, in place of the 24-methylenecycloartanol ferulic acid ester, oils and fats containing other organic acid esters of 24-methylenecycloartanol are used as raw materials.

As described above, 24-methylenecycloartanol, 2
When a raw material oil or fat obtained by concentrating oryzanol, an organic acid ester containing 4-methylenecycloartanol ferulic acid ester, is used as a raw material for the method of the present invention, it is necessary to remove fatty acids present therein in advance.

This fatty acid can be removed by a conventional method such as a distillation method, an esterification method, a metal salt method, or a treatment method with an amine salt or an ammonium salt.

Next, in the method of the present invention, as an anhydrous organic solvent, hexaalkylphosphoramide, dialkyl sulfoxide, aliphatic hydrocarbon, aromatic hydrocarbon, nuclear substituted aromatic compound having a boiling point of 98 to 250°C, preferably 100 to 200°C is used. Group hydrocarbons, alcohols, ethers, ketones, halogenated alkanes, etc. are used.

This material is used in a substantially anhydrous state.

The presence of water is undesirable because decomposition products and byproducts of unknown composition are produced.

Specific examples of solvents used in the method of the present invention include n-hebutane, n-octane, isooctane, isononane, methylcyclohexane, toluene, xylene, ethylbenzene, inglobilbenzene, diethylbenzene, sec-butylbenzene, amyl chloride, dibromo Ethylene, dichloropentane, trichloroethane, trichloropropane, tetrachloroethane, monochlorobenzene, 0-dichlorobenzene, monochlorotoluene, monobromobenzene, dichloroethyl ether, n-7” ethyl alcohol, isobutyl alcohol, in-amyl alcohol, tertiary amyl Alcohol, fusel oil, 3-methoxybutyl alcohol, n-hexyl alcohol, 2-methylpentanol-1,2-ethylbutyl alcohol, sec-heptyl alcohol, heptanol-3, sec-octyl alcohol, methyl n-probyl Ketone, methyl n-butyl ketone, diethyl ketone, methyl isobutyl ketone, methyl n-amyl ketone, ethyl butyl ketone, methyl hexyl ketone, imbutyl ketone, cyclohexanone,
Methyl cyclohexanone, n-butyl ether, dioxane, dimethyl dioxane, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, ethylene glycol ethyl ether, dimethyl sulfoxide,
Examples include hexamethylphosphoramide.

Further, in the method of the present invention, it is necessary to use a sodium or potassium alcoholate as a catalyst, and this alcoholate is preferably one derived from an alcohol having 3 to 8 carbon atoms.

These include potassium tert-butyrate,
Particular mention may be made of potassium sec-butyrate, potassium n-butyrate, potassium tert-pentylate, sodium t-butyrate, but also sodium sec-butyrate, sodium n-butyrate, sodium n-octylate, potassium n-octylate, potassium 2-butylate. -Ethylhexylate and the like can also be used.

These catalysts are usually used in amounts ranging from 1 to
400%, preferably in the range of 10 to 200%.

As a catalyst, such a sodium or potassium alcoholate alone is sufficient, but if necessary, metallic sodium or metallic potassium can be used in combination to accelerate the reaction.

To suitably carry out the method of the present invention, 1 to 3 raw material compounds are used.
Dissolve or suspend in 0 times the amount of anhydrous organic solvent, add the required amount of catalyst, and incubate at 100 to 160°C for 20 minutes to 15 minutes.
The reaction time is preferably 1 to 10 hours.

In this way, 24-methylenecycloartanol or its organic acid ester can be isomerized to cyclobranol or its organic acid ester at a conversion rate of 27 to 47.3%.

For example, when commercially available oryzanol with a cyclobranol content of 6% or less is treated by the method of the present invention, cyclobranol is reduced to 1%.
It can be increased by up to 5-30%.

In the method of the present invention, when a sodium or potassium alcoholate is used alone as a catalyst, cyclopranol organic acid ester is produced from 24-methylenecycloartanol organic acid ester, and cyclopropanol organic acid ester is produced from 24-methylenecycloartanol. From 24-methylenecycloartanol and its organic acid ester, cyclobranol and its organic acid ester can be obtained.

On the other hand, when an alcoholate and metallic sodium or metallic potassium are used together as a catalyst, cyclobranol can be obtained from any of 24-methylenecycloartanol, its organic acid ester, or a mixture thereof.

On the other hand, when an alcohol is used as a solvent, the final product is cyclobranol regardless of the type of catalyst or the raw material compound.

With other solvents, either cyclobranol or its organic acid ester can be obtained depending on the raw material compound.

According to the method of the present invention, when 24-methylenecycloartanol or its organic acid ester coexists with other sterols and triterpene alcohols, 24-methylenecycloartanol can be produced without causing decomposition or side reactions of these substances. Alternatively, only the organic acid ester thereof can be selectively rearranged to cyclobranol or the organic acid ester thereof, and therefore there is an advantage that the desired product can be obtained in high yield.

Cyclobranol or its organic acid ester obtained by the method of the present invention can be isolated and crystallized by a conventional method if necessary.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 15% by weight of campesterol, 1% by weight of stigmasterol, 4% by weight of β-sitosterol, 3% by weight of cycloartanol, 38% by weight of cycloartenol, 3% by weight of 24-methylenecycloartanol, and 3% by weight of cycloartanol. 1.6 g of oryzanol containing 1% by weight of branol was suspended in 20 d of dimethyl sulfoxide, 3.55 i' of potassium-tert-butyler was added thereto, and the mixture was stirred while heating at 100 to 110° C. for 5 hours.

After the reaction was completed, the reaction solution was searched by range chromatography (developing solvent: chloroform:benzene 1:3), and as a result, no decomposition of sterol and triterpene alcohol-ferulic acid ester was observed.

Next, the reaction solution was neutralized with dilute hydrochloric acid and concentrated under reduced pressure. 60 ml of 2N caustic potash ethanol solution was added to the obtained crystal residue, and after saponifying by heating under reflux at 81°C for 6 hours, water was added, and then Extracted with ethyl ether.

The generated potassium ferulic acid salt was removed to the aqueous layer, and the ethyl ether layer was washed with water, dehydrated, concentrated under reduced pressure, and dried. The crystals were dissolved in hexane and the components of the neutral part of oryzanol were analyzed by gas chromatography. did.

The gas chromatography equipment used was manufactured by Hitachi, and the measurement conditions were: Column: 3 m long x 2 m long, Support: Chromosolve W.
-HP (80-100 mesh) with 1% silicone oil (silicon Cv-1) adsorbed (product of Gascro Industries Co., Ltd.), column temperature 240°C, detection temperature 270°C.
℃, carrier gas: helium, and a flow rate of 60 ml/min.

The retention time (minutes) of each component was as follows.

Campesterol 6.56, stigmasterol 7.0
7, β-sitosterol 8.11, cycloartanol 8.53, cycloartenol 9.20, 24-methylenecycloartanol 10.56, cyclobranol 1
It was 2.23 minutes.

Table 1 shows the analysis results of this component and the rearrangement rate from 24-methylenecycloartanol ferulate to cyclobranol ferulate.

Example 2 Campesterol 0.8%, cycloartanol 1.5
%, cycloartenol IO. 1.51 of a mixture of acetate esters of 2% and 87.5% of 24-methylenecycloartanol were suspended in 30 ml of ortho-dichlorobenzene, and 0.0. 9 f was added and stirred while heating at 140°C for 5 hours.

After the reaction was completed, the reaction mixture was cooled, neutralized with dilute sulfuric acid, and concentrated under reduced pressure.

Water was added to the obtained crystalline residue, and the mixture was extracted with chloroform.

The chloroform layer was washed with water, dehydrated, and concentrated under reduced pressure.

The yield of the obtained crystals was 1.41S', which was 94%.

The crystals were dissolved in hexane, and the components were analyzed by gas chromatography.

The results showed campesterol 0.8%, cycloartanol 1.5%, cycloartenol 10.2%, 24-
The acetate esters were 49.3% methylenecycloartanol and 38.2% cyclobranol.

The conversion rate of 24-methylenecycloartanol acetate to cyclobranol acetate was 43.6%.

Example 3 2 g of a mixture of acetic esters (neutral part equivalent: 1.82 g) consisting of 12% campesterol, 6% cycloartanol, 38% cycloartenol, and 44% 24-methylenecycloartanol was added to orthodichlor. benzene 20
ml and methachlorotoluene (20 ml), 2 fI of sodium-tert-butyrate and 0.5 g of sodium metal were added thereto, and the mixture was heated and reacted at 140° C. for 10 hours.

After the reaction is complete, cool and add 50 ml of absolute ethanol to the reaction solution.
After pouring into the solution while stirring, the solution was neutralized with dilute sulfuric acid and concentrated under reduced pressure.

Water was added to the obtained residue and extracted with chloroform.

After washing the chloroform layer with water, it was dehydrated and dried, concentrated under reduced pressure and dried.

The yield of crystals was 1.6 g, which was 88%.

The crystals were dissolved in hexane, and the components were analyzed by gas chromatography.

The results were 12% campesterol, 6% cycloartanol, 38% cycloartenol, 27% 24-methylenecycloartanol, and 17% cyclobranol.

The conversion rate of 24-methylenecycloartanol acetate to cyclobranol was 38%.

Example 4 2 g of palmitic acid ester of 12% campesterol, 6% cycloartanol, 38% cycloartenol, and 44% 24-methylenecycloartanol were suspended in a mixed solvent of 20 ml of methylhexyl ketone and 20 ml of normal hexyl alcohol. To this, 4v of potassium sec-butyrate was added and reacted at 130°C for 8 hours.

After that, the same gas chromatography operation as in Example 1 was carried out, and the resulting components were 12% campesterol, 6% cycloartanol, 38% cycloartenol, 24%
- Methylene cycloartanol 30%, cyclobranol 14% tarred.

The conversion rate of 24-methylenecycloartanol palmitate ester to cyclobranol was 31%.

Example 5 24-methylenecycloartanol-orthobutyric acid ester 2
g was suspended in a mixed solvent of 10 ml of sec-butylbenzene and 20 ml of dimethyl sulfoxide, 1.51 g of potassium tert-butylate and 1 g of potassium n-butylate were added thereto, and the mixture was heated and reacted at 110° C. for 5 hours.

After the reaction was completed, the mixture was neutralized with dilute hydrochloric acid, the solvent was concentrated under reduced pressure, water was added, and extraction was performed with chloroform. The chloroform layer was washed with water, dehydrated, concentrated under reduced pressure, and dried to obtain crystals of 1.99%.

The yield was 95%.

The crystals were dissolved in hexane, and the components were analyzed by gas chromatography.

The crystal components were 58.2% of 24-methylenecycloartanol-orthobutyric acid ester and 41.8% of cyclobranol-orthobutyric acid ester.

That is, the conversion rate from 24-methylenecycloartanol-orthobutyric acid ester to cyclobranol-orthobutyric acid ester was 41.8%.

Example 6 24-methylenecycloartanol 1.55',24-
Methylene cycloartanol ferulate ester 0.5
A mixture of 0.5 P of S', 24-methylenecycloartanol benzoate was suspended in 20 ml of n-butanol, and 41 potassium n-butyrate was added to give 11
The mixture was heated and reacted at 0°C for 6 hours.

Thereafter, the components were analyzed by gas chromatography in the same manner as in Example 1, and the results were 60.2% of 24-methylenecycloartanol and 39.8% of cyclobranol.

The dislocation rate was 39.8%. Example 7 Campesterol ferulate ester 0.2g, cycloartenol ferulate ester 0.2g. 2g, 24-methylenecycloartanol 0.14g, 24-methylenecycloartanol isobanilic acid ester 0.21
A mixture of 0.2 g of f124-methylenecycloartanol ferulic acid ester (total amount 0.95 g, neutral part equivalent amount 0.72 g) was mixed with a mixed solvent of 10 ml of ethylene glycol dipropyl ether, 20 ml of orthodichlorobenzene, and 5 ml of toluene. To this was added 0.5 g of potassium secondary platylate and 0.21 g of sodium metal, and the mixture was heated and reacted at 120° C. for 6 hours.

After the reaction was completed, the reaction solution was neutralized with dilute hydrochloric acid, and then treated in the same manner as in Example 1. The yield of crystals was 0.7 g, which was 97%.

The crystals were dissolved in hexane and analyzed using gas chromatography. The results were 19.4% campesterol, 19.5% cycloartenol, 36.1% 24-methylenecycloartanol, and 25.0% cyclobranol. Met.

The dislocation rate was 40.9%.

Examples 8-28 A mixture of 12% cycloartenol and 88% 24-methylenecycloartanol, butyric acid, inpropionic acid, monobutyl succinate, monomethyl adipate, methylethyl acetate, citric acid, α-ketoglutaric acid, ethoxybenzoic acid Monoesters and diesters of acids, benzoic acid, hydrocinnamic acid, vanillic acid, monoethyl phthalate, phenyl acetic acid, mandelic acid, naphthenic acid, nicotinic acid, p-aminobenzoic acid, succinic acid, azelaic acid, phthalic acid, terephthalic acid. 21 of each in 20 ml of orthodichlorobenzene
, dichloroethyl ether 10ml, ethylbenzene 1
The suspension was suspended in 0 ml of a mixed solvent, 12 portions each of potassium and tert-butyrate were added thereto, and the mixture was heated at 130° C. for a specified period of time to react.

After the reaction was completed, the reaction solution was examined using thin-layer chromatography (developing solvent: chloroform:benzene 1:3), and as a result, it was found that each organic acid ester was slightly decomposed.

Next, after neutralizing the reaction solution with diluted hydrochloric acid, the solvent was concentrated under reduced pressure, and the resulting crystal residue was added with a solution of 4 N
After adding 0 ml and heating under reflux at 81°C for 4 hours for saponification decomposition, water was added and extracted with chloroform to transfer the organic acid potassium salt to the aqueous layer and the neutral part of the triterpene alcohol to the chloroform layer.

After washing the chloroform layer with water, it was dehydrated and dried, and then concentrated and dried under reduced pressure.

The obtained crystals were dissolved in hexane, and component analysis was performed using gas chromatography.

The results and the conversion rate of 24-methylenecycloartanol organic acid ester to each cyclobranol organic acid ester are shown in Table 2.

Example 29 Campesterol 17%, stigmasterol 3%, β
- 1.51 of a mixture of 10% sitosterol, 5% cycloartanol, 32% cycloartenol, and 33% 24-methylene cycloartanol was added to 1 1 of methachlorotoluene.
The suspension was suspended in a mixed solvent of 0ml and 20rrLl of 1-chlorooctane, 0.5P of potassium tertiary pentylate and 0.41L of potassium metal were added thereto, and the mixture was reacted by heating at 120°C for 6 hours.

After the reaction is complete, cool and add 50 ml of absolute ethanol to the reaction solution.
After pouring into the solution while stirring, the solution was neutralized with diluted hydrochloric acid and concentrated under reduced pressure.

Water was added to the obtained residue and extracted with chloroform.

The chloroform layer was washed with water, dehydrated, concentrated under reduced pressure, and dried.

The yield of crystals was 1.42 g, which was 94%.

The crystals were dissolved in hexane, and the components were analyzed by gas chromatography.

The results were campesterol 17%, sticmasterol 3%, β-sitosterol lO%, cycloartanol 5%, cycloartenol 32%, 24-methylenecycloayortanol 18%, and cyclobranol 15%. .

The conversion rate of 24-methylenecycloartanol to cyclobranol was 45%.

Examples 30 to 37 24-methylenecycloartanol (Example 30), and baelatormic acid (Example 31), cinnamic acid (Example 32), and allocinnamic acid (Example 3) of 24-methylenecycloartanol
3), coumaric acid (34), mandelic acid (35),
Benzoylacetic acid (36), α-naphthalic acid (37)
) of each ester with 15 m of dimethyl sulfoxide.
1, and 1.5 g of potassium tertiary petyrate is suspended in this.
was added and reacted by heating at 120°C for 5 hours.

After the reaction was completed, the reaction solution was neutralized with dilute sulfuric acid, and then Example 1
Table 3 shows the results of measuring the components by gas chromatography after the same treatment as above and the conversion rate (%) of 24-methylenecycloartanol and its respective organic acid esters to cyclobranol and cyclopranol each organic acid. It was shown to.

Example 38 100 parts by weight of degummed and dewaxed rice bran oil with an acid value of 24.5 was mixed with 10% caustic soda and soda carbonate in the presence of 100 parts by weight of 50% ethanol and 7350 parts by weight of Hexa. The oryzanol-containing alcohol aqueous solution obtained by deoxidizing with an aqueous solution was neutralized to pH 7.2 with a caustic soda aqueous solution, and then concentrated under reduced pressure and dried.

This concentrated dry product (oryzanol content was 58%, this oryzanol contained 46% of 24-methylene-cycloartanol ferulic acid ester, and the content of cyclobranol ferulic acid ester was 1%).

) was suspended in a mixed solvent of 20 ml of inbutanol and 2 oml of ethyl butyl ketone, 2.5 f of potassium-sec-butylene was added thereto, and the mixture was heated and reacted at 110° C. for 10 hours.

After the reaction was completed, 1.7f of mixed crystals of sterol and triterpene alcohol containing 16% cyclobranol was obtained by extraction and purification using a conventional method.

The yield was 58%. The conversion rate of 24-methylenecycloartanol ferulic acid ester to cyclobranol was 32.6%.

Example 39 Wheat germ dark oil (oryzanol content 15%, 24-methylene-cycloartanol ferulate ester content in this oryzanol 40%, cyclobranol ferulate ester content was 0) was prepared in a conventional manner. After methyl esterification and removal of fatty acid methyl by distillation,
The distillation residue was neutralized to pH 7.0 with an aqueous caustic potash solution and concentrated to dryness.

5 g of this concentrate (oryzanol content 25%, 24-methylenecycloartanol ferulate ester content 40%, cyclobranol ferulate ester content O in this oryzanol) was added to 20 rn of parachlorotoluene.
2 g of sodium tert-butyrate and 1 v of sodium metal were added thereto, and the mixture was heated and reacted at 140° C. for 8 hours.

After the reaction was completed, the mixture was extracted and purified by a conventional method to obtain 0.625' mixed crystals of sterol and triterpene alcohol containing 15% cyclobranol and 25% 24-methylenecycloartanol.

The yield was 49.6%, and the conversion to cyclobranol was 37.5%.

Example 40 Rice bran dark oil (with oryzanol content 20.5%,
Oryzanol containing 41.2% of 24-methylenecycloartanol and 24-methylenecycloartanol ferulic acid ester, and 0.1% of cyclobranol and hycyclobranol ferulic acid ester) 51 was added to an aqueous calcium hydroxide solution. After neutralization to pH 7.5, dehydration and drying, suspension in 25 ml of dimethyl sulfoxide, and 1.5 ml of potassium-tert-butylene. and potassium metal 2.
52 was added thereto, and the mixture was heated and reacted at 120°C for 8 hours.

After the reaction is completed, extraction and purification are carried out using conventional methods to obtain 15.8% cyclobranol, 25.4% 24-methylenecycloartanol, and 3% cycloartenol.
7.5%, cycloartanol 4.8%, β-sitosterol 3.3%, campesterol 13.2% mixture 0. 6 4? I got it.

The yield was 62.4%, and the conversion rate to cyclobranol was 38.1%.

Claims (1)

[Scope of Claims] 1. In producing cyclobranol or its organic acid ester by isomerizing 24-methylenecycloartanol or its organic acid ester, the raw material compound is converted into sodium alcoholate or potassium alcoholate in an anhydrous organic solvent. A method for producing cyclobranol or an organic acid ester thereof, which comprises heating to a temperature in the range of 100 to 160°C in the presence of. 2. The method according to claim 1, wherein the sodium alcoholate or the potassium alcoholate is an alcoholate derived from an alcohol having 4 to 8 carbon atoms. 3. The method according to claim 2, wherein the alkonyl having 4 to 8 carbon atoms is n-butyl alcohol, sec-butyl alcohol, tertiary-butyl alcohol, or tertiary-pentyl alcohol. 4. The method according to claim 1, wherein the anhydrous organic solvent is a dialkyl sulfoxide aromatic hydrocarbon, a nuclear substituted aromatic hydrocarbon alcohol, an ether, a ketone, or a halogenated alkane.