JPS5843400B2 - Method for producing cyclobranol organic acid ester - Google Patents

Description

Detailed Description of the Invention The production method of the present invention involves subjecting 24-methylenecycloartanol organic acid ester or a substance containing 24-methylenecycloartanol organic acid ester to a heating reaction in the presence of iodine or iodine and iodide. This invention relates to a method for isomerizing cyclobranol to an organic acid ster.

As a result of detailed research by the present inventor, it was discovered that when free 24-methylenecycloartanol was subjected to a heating reaction in the presence of iodine as a catalyst or iodine and iodide, no rearrangement to cyclobranol occurred. It was recognized that it is an essential condition to substitute the hydroxyl group bonded to the carbon 3 position of 24-methylenecycloartanol at the ester position with an organic acid.

That is, by subjecting organic acid esters, including ferulic acid esters of 24-methylenecycloartanol, to a heating reaction in the presence of iodine alone or a mixture of iodine and iodide as a catalyst, cyclobranes can be easily and in high yields. We were able to establish a new method for rearrangement, or in other words, conversion, to a nol organic acid ester.

The method of the present invention not only does not generate by-products due to the cleavage of the cyclopropane ring of organic acid esters of 24-methylenecycloartanol and cyclobranol at high temperatures, unlike the conventional acid catalyst method, but also does not produce by-products due to the cleavage of the cyclopropane ring of the organic acid ester of 24-methylenecycloartanol and cyclobranol. An advantage is that methylene cycloartanol organic acid ester and cyclobranol organic acid ester do not have the disadvantage of decomposing into 24-methylene cycloartanol and cyclobranol and organic acids, respectively.

The organic acid of the organic acid ester shown above is a saturated or unsaturated C2-C4o aliphatic, aromatic, alicyclic, heterocyclic, or saccharide mono-, di-, or tricarboxylic acid.

These mono-, di-, and tricarboxylic acids have O to 4 side chains such as aliphatic, aromatic, or alicyclic hydrocarbon groups, ketone groups, hydroxyl groups, alkoxyl groups, ether groups, or ester groups. It is an organic acid in the bound form.

Representative compound names of these suitable organic acids are illustrated below.

Aliphatic monocarboxylic acids include formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, methylethyl acetate, trimethylacetic acid, caproic acid, caprylic acid, pelargonic acid, capric acid, palmitic acid,
Stearic acid, etc. are used.

Aliphatic dicarboxylic acids include malonic acid, succinic acid, cultaric acid, methylsuccinic acid, ethylmalonic acid, dimethylmalonic acid, adipic acid, pimelic acid, speric acid, azelaic acid, sebacic acid, or C1 to C6 alkyl groups of these acids. Monoester etc. are used.

Aliphatic oxycarboxylic acids include gelcholic acid and lactic acids (α-oxypropionic acid, β-oxypropionic acid)
, oxymalonic acid, menoxalic acid, malic acid, tartaric acid, ita liquor, pentaacid, oxyparaconic acid (itartrate lactone),
Citric acid, isocitric acid, alloisocitric acid, or mono- or diesters of C1 to C6 alkyl thereof are used.

As the aliphatic ketocarboxylic acid, there may be used photochromic acid, acetoacetic acid, acetone dicarboxylic acid, α-ketoglutaric acid, levyuric acid (γ-ketonic acid), or mono- or diesters of C1 to C6 alkyl thereof.

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

Aromatic heptanocarboxylic acids and derivatives thereof include benzoic acid, methylbenzoic acid, ethylbenzoic acid, oxybenzoic acids (e.g. salsic acid, methoxybenzoic acid, ethoxybenzoic acid), dioxybenzoic acids trioxybenzoic acids (e.g. gallic acid), benzenedicarboxylic acids (e.g. phthalic acid, inphthalic acid, terephthalic acid, or C1-C1o alkyls thereof) or monoesters of aromatic groups), benzene trigalponic acids (e.g. trimesic acid, trimellitic acid, hemimellitic acid or mono- or diesters of C1-C1o alkyl groups or aromatic groups thereof), having side chains Benzenecarboxylic acids (e.g. haphenylacetic acid, hydroatrobic acid, hydrocinnamic acid, atorbic acid, cinnamic acid, allocinnamic acid, coumaric acid, mandelic acid, ferulic acid, benzoyl acetic acid, etc.)
etc. are used.

As the alicyclic carboxylic acid, cyclopropane mono-1
and di-carboxylic acids, mono-4 di-carboxylic acids of cyclopropene, naphthenic acid, naphthalic acid, quinic acid,
Shikimic acid or monoesters of these C1 to C1o alkyl groups or aromatic groups are used.

Other compounds include nicotinic acid, pantothenic acid, p
-Amine benzoic acid, folic acid, ascorbic acid, various α-
Carboxylic acid compounds of amino acids (aspartic acid, glutamic acid, oxyglutamic acid, etc.) and sugars (such as D
-gluconic acid, 5-keto-D-gluconic acid, D-gulonic acid, L-idonic acid, 2-keto L-gulonic acid, 2-keto L-gulonic acid, etc.).

Among the various organic acids shown above, organic acids having an aliphatic group as a linear or side chain have different structures and exceptions, but in general, saturated types are preferable to unsaturated types.

Among the starting materials of the present invention, the content of 24-methylenecycloartanol organic acid ester refers to the following actual conditions.

That is, a mixture of at least two types of 24-methylenecycloartanol organic acid ester, a mixture of at least one type of 24-methylenecycloartanol organic acid ester and at least one type of other triterpene alcohol organic acid ester. , a mixture of at least one type of 24-methylenecycloaltanol organic acid ester and at least one type of sterol (or sterine) organic acid ester, 24-methylenecycloalknol organic acid ester and other triterpene alcohol organic acid ester and one or more of each of the three sterol organic acid esters, oryzanol containing 24-methylenecycloartanol ferulic acid ester, 24-
Examples include 24-methylenecycloartanol organic acid ester containing methylenecycloartanol ferulic acid ester or oils and fats containing oryzanol.

The ferulic acid ester of cyclobranol and other organic acid esters produced by the method of the present invention are effective for autonomic nervous system imbalance, menopausal disorders, chronic gastritis, irritable bowel disease,
Effective for peptic ulcers.

Furthermore, it is an effective drug for treating indeterminate physical complaints of the gastrointestinal system and neuropsychiatric system, as well as sequelae of head trauma and neck injury.

Vegetable oils such as rice bran oil, rice bran germ oil, wheat germ oil, peanut oil, sesame oil, corn oil, and olive oil originally contain about 0.1 to 2 of various sterols, triterpene alcohols, or their ferulic acid esters. Contains %.

Generally, commercially available pharmaceuticals called gamma-oryzanol or oryzanol are effective for climacteric disorders, autonomic imbalance, anti-stress effects, and the like.

Gamma-oryzanol or oryzanol pharmaceuticals are not a single product, but a mixture of ferulic acid esters of various sterol triterpene alcohols.

Table 1 shows the results of analysis by gas chromatography of the neutral parts of sterol and triterpene alcohol after saponification and decomposition of commercially available oryzanol and removal of ferulic acid by the present inventor.

As shown in Table 1, the neutral part of commercially available oryzanol contains only 0 to 6% of cyclobranol.

Oryzanol's active ingredient is cyclobranol ferulic acid ester.

Oryzanol having these compositions is contained in the above-mentioned vegetable oils in an amount of about 0.1 to 2%.

The oils and fats containing 24-methylenecycloartanol ferulic acid ester or oryzanol shown as the actual starting materials are fatty acids, esters of monohydric to trihydric alcohols of fatty acids, alkali metals or alkaline earths of fatty acids. It consists of at least one of salts of similar metals or heavy metals, monovalent to tetravalent amines and ammonium salts of fatty acids, or wax components.

Further, the actual situation will be described in detail below.

In the deoxidation process of vegetable oil, that is, for the purpose of refining the vegetable oil and obtaining edible neutral oil, the free fatty acids in the raw vegetable oil are converted into alkaline soap and separated by centrifugation. to be called.

The crude fatty acid obtained by treating this foot with an inorganic acid such as sulfuric acid or hydrochloric acid is called dark oil.

Since oryzanol has the property of being well soluble in alkaline fats and oils, oryzanol is transferred from the raw oil and concentrated in the foots and dark oil obtained as a by-product in the deoxidation process of vegetable oil, and the amount is about 3 to 15 times that of the original vegetable oil. It is concentrated and contains about 1 to 30% oryzanol, and is preferable as a raw material.

A residue concentrate obtained by separating the fatty acids in the dark vegetable oil by distillation, or a residue concentrate obtained by esterifying the fatty acids in the dark vegetable oil with a lower alcohol and then separating it by distillation, or a vegetable oil treated with an ion exchange resin. The obtained oryzanol-containing oil contains 2 to 70% oryzanol,
These are suitable raw materials.

Alternatively, vegetable oil can be obtained by separating the water-containing solvent from a solution of a water-containing polar solvent containing oryzanol obtained by carrying out 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, which is also a suitable raw material.

24 shown above as an actual starting material for the production method of the present invention
-methylenecycloartanolIt goes without saying that oils and fats containing 24-methylenecycloartanol organic acid ester, which is composed of the other types of organic acids mentioned above, instead of ferulic acid ester, are also suitable raw materials.

The production method of the present invention involves dissolving or suspending 24-methylenecycloartanol organic acid ester or a substance containing 24-methylenecycloartanol organic acid ester in an organic solvent by using an organic solvent suitable for dissolving or suspending 1 to 30 times the organic solvent. The catalyst, iodine alone or a mixture of iodine and iodide, is added to the raw material at a rate of 0.
1 to 300%, preferably 1 to 100%, and the reaction temperature is 2
0-200℃, preferably 30-150℃, reaction time 2
By reacting for 0 minutes to 15 hours, preferably 1 to 10 hours, 24-methylenecycloartanol organic acid ester can be converted to cyclobranol organic acid ester in a yield of 30 to 80% without side reaction decomposition. did it.

For example, the cyclobranol ferulic acid ester content, which was present in conventional commercially available oryzanol at only about 0 to 6%, could be increased to 10 to 30% by the method of the present invention.

In addition, oryzanol containing a large amount of cyclobranol ferulic acid ester could be obtained by a conventional method from the 24-methylenecycloartanol ferulic acid ester-containing fats and oils treated by the method of the present invention.

In addition, cyclobranol ferulic acid ester could be isolated and crystallized by a conventional method from the 24-methylenecycloartanol ferulic acid ester-containing material treated by the method of the present invention.

In the production method of the present invention, it is most preferable to use iodine alone as a catalyst, but inorganic and organic iodides may be used together with iodine.

These inorganic and organic iodides include potassium iodide,
Sodium iodide, robidium iodide, lithium iodide, cesium iodide, ammonium iodide, strontium iodide, barium iodide, calcium iodide, aniline hydride iodide, dimethylaniline hydride iodide, tetramethylammonium iodide, etc. Inorganic and organic iodides having a property of well dissolving iodine coexisting in the reaction system are preferred.

The coexistence of iodide accelerates the solubility of iodine, accelerates the reaction rate,
It is preferable to conserve iodine and to generate iodine when the starting material is a weakly acidic material such as dark oil, for example, in the presence of free fatty acids.

The solvent used in the production method of the present invention is at least one of C1 to C1□ hydrocarbons, halogenated hydrocarbons, esters, ketones, ethers, nitro compounds, sulfur-containing compounds, nitrogen-containing compounds, and organic acids. More than one type is used.

A specific example of this will be illustrated next.

Namely, hexane, octane, heptane, cyclobencune, methylcyclopencune, cyclohexane, methylcyclohexane, benzene, toluene, xylene, isopropylbenzene, tert-butylbenzene, ethylbenzene, chloroform, carbon tetrachloride, dichloroethane, dichlorinated propylene, Propane dichloride, trichloroethane, chlorooctane, tetrachloroethylene, bromoform, ethylene dibromide, ethane dibromide, chlorobenzene, chlorotoluene, bromobenzene, trichloroacetic acid, dichloroacetic acid, methyl acetate, ethyl acetate, propyl acetate, Butyl acetate, amyl acetate, 2-ethylbutyl acetate, benzyl acetate, methyl formate, ethyl formate, butyl formate, methyl butyrate, ethyl butyrate, propyl butyrate, nitromethane, nitroethane, nitropropane, dinitropropane, nitrobenzene, acetone, methyl ethyl ketone, methyl propyl Ketone, methyl butyl ketone, diethyl ketone, ethyl butyl ketone, pentanedione, acetonylacetone,
Isopropyl ether, butyl ether, dioxane,
Dimethyl dioxane, ethylene glycol monomethyl ether (methyl cellosolve), ethylene glycol monoethyl ether (cellosolve), ethylene glycol monobutyl ether (butyl cellosolve), diethylene glycol monomethyl ether, formic acid, acetic acid, propionic acid, butyric acid, carbon disulfide, dimethyl sulfoxide, Examples include acetonitrile, hexamethylphosphoramide, and the like.

However, when alcohols and amines are used as solvents, the starting material 24-methylenecycloartanol organic acid ester decomposes during the heating reaction, producing free 24
-Produce alcohol esters of methylenecycloartanol and organic acids or amine salts of organic acids.

Therefore, since free 24-methylenecycloartanol is not rearranged to cyclobranol in the iodine catalyst of the present invention, alcohols and amines are unsuitable as organic solvents in the present invention.

After the reaction was completed, the iodine in the catalyst could be easily removed by washing with an aqueous solution of sodium thiosulfate, potassium thiosulfate, potassium oxalate, sodium oxalate, potassium iodide, sodium iodide, ammonium iodide, or the like.

The cyclobranol organic acid ester obtained by the production method of the present invention could be confirmed by gas chromatography, column chromatography, or recrystallization method.

Alternatively, it could be confirmed by gas chromatography or column chromatography after the reaction-completed cyclobranol organic acid ester was saponified and decomposed to form cyclobranol.

Furthermore, the cyclobranol obtained by the above procedure was trimethylsilylated and then confirmed by gas chromatography.

Examples 1 to 12 21 pieces of commercially available gamma-oryzanol (product of Company A shown in Coating-1 above) were collected into respective flasks, and hexane, toluene, benzene, chloroform, bromopropylene, trichloroethylene, and tetrachloride were added to each flask. Carbon, carbon disulfide, nitromethane, acetic acid ethylacetone, and isopropyl ether were added in an amount of 50 TL each, and 0.11 iodine was added thereto, followed by a heating reaction at each temperature for 4 hours.

After cooling, 50ml of ethyl acetate was added to each and stirred.
After washing each organic solvent solution with % sodium thiosulfate swimwear solution,
It was further washed with water and concentrated under reduced pressure at a temperature below 40°C to obtain a crystalline residue.

When this crystalline residue was observed by thin layer chromatography (developing solvent: chloroform:benzene 1:3), no decomposition of the oryzanol ester was observed.

50 rrL of a 2N caustic potash ethanol solution was added to 1 ton of the above crystal residue table, and the solution was saponified and decomposed by heating under reflux for 6 hours.The solution was immediately poured into water to stop the reaction, and then extracted with ethyl ether.

The generated potassium ferulate was removed to an aqueous layer, and the ethyl ether layer was dehydrated and dried. After distilling off the ethyl ether, the obtained crystals were dried.

Each crystal was dissolved in hexane, and the components were analyzed by gas chromatography.

The gas chromatography equipment used was made by Hitachi, and the measurement conditions were: Column: diameter 3 mm x length 2 doors, carrier: chloroform W-HP (80 to 100 mesh) adsorbed with 1% silicone oil (silicon 0v-1). (Gas Kuro Kogyo Co., Ltd. product), column temperature 240℃, detection temperature 27
0°C, carrier gas: helium, flow rate 6o11L/
Measured in minutes.

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

Campesterol 6.56, stigmasterol 707
．． β-sitosterol 8.11, cycloartanol 8
．． 53, cycloartenol 9.20.

24-methylenecycloartanol was 10.56 minutes, and cyclobranol was 12.23 minutes.

The results are shown in Table 2. Example 13 24-methylenecycloartanol acetate 0.7
f was dissolved in 35-benzene, 0.05 f of iodine was added thereto, and the mixture was reacted at 80°C for 4 hours with stirring.

After the reaction was completed, the crystals obtained were quickly cooled, washed with a 1% sodium thiosulfate aqueous solution, washed with water, and dried.
55', and its components were analyzed by gas chromatography.

The result was cyclobranol acetate 46%, 24%
-The composition was 54% of methylene cycloartanol acetate, and no other components were observed.

That is, it was confirmed that 46% of 24-methylenecycloartanol acetate was rearranged to cyclobranol acetate.

Example 14 24-methylenecycloartanol butyrate 1.1
? was dissolved in a mixed solvent of 20rfLl of butyric acid and 20TfLl of toluene, and 0.03S' of iodine and 0.1fL of sodium iodide were added to this. was added and reacted at 80°C for 2 hours with stirring.

Immediately after the reaction, the solvent was concentrated under reduced pressure at below 50°C, the resulting crystalline residue was dissolved in hexane, the hexane layer was washed with a 1% aqueous sodium thiosulfate solution, then water, and after drying, the components were analyzed by gas chromatography. I did this.

The result was cyclobranol butyrate ester 48%, 24
-Methylene cycloartanol butyric acid was 52%, and no other components were observed.

That is, the rearrangement rate from 24-methylenecycloartanol butyrate to cyclobranol butyrate is 4
It was 8%.

Example 15 Ferulic acid ester 2? consisting of 12% campesterol, 6% cycloartanol, 38% cycloartenol, and 44% 24-methylenecycloartanol. was suspended in nitrobenzene 20171/tonitroethane 20WLl, and iodine 0.05f? and potassium iodide 0.15
f? was added and reacted at 70°C for 3 hours with stirring.

After the reaction is complete, add 30 ml of hexane, stir, and add 2%
The mixture was washed with an aqueous potassium oxalate solution, then washed with water, dehydrated and dried, and then concentrated under reduced pressure at 50°C or lower.

The obtained crystals had a temperature of 1.93F, and 1.9y of these crystals were suspended in 60 WL of a 2N caustic potash ethanol solution, heated under reflux for 6 hours for saponification and decomposition, and then the liquid was poured into water and then extracted with ethyl ether.

The generated potassium ferulate was removed to an aqueous layer, the ethyl ether layer was dehydrated and dried, and after distillation, the obtained crystals were dried.

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

As a result, campesterol was 12%, cycloartanol was 6%, cycloartenol was 38%, 24-methylenecycloartanol was 23%, and cyclobranol was 21%.

The rearrangement rate from 24-methylenecycloartanol to cyclobranol was 47.7%.

As a result of repeated recrystallization of 1.21 crystals of the composition of the mixture of sterine and triterpene alcohol containing cyclobranol from a mixed solvent of acetone-methanol (1:1), 0.15P of cyclobranol crystals were obtained.

This product showed a single peak in gas chromatography.

Melting point 156.5-157.5℃, specific optical rotation [α)j'-
+-39 sentences 1.0, CHCla): RfO,
25 [TLC (thin layer chromatography) of silica gel G (Merck & Co., Ltd.), developing solvent benzene-chloroform 3:
1); Calculated value as elemental analysis value C3, H5□0 C84
, 48% Hll, 89% actual value C84, 52% H
ll, 83% Examples 16-37 Each organic acid ester of a mixture of 12% cycloartenol and 88% 24-methylenecycloartanol, namely palmitic acid, monobutyl succinate, hydrocinnamic acid, monomethyl adipate, Isobutyric acid, methylethyl acetic acid, citric acid, α-ketogeltanic acid, ethoxybenzoic acid, benzoic acid, isobanilic acid, monoethyl phthalate, phenylacetic acid, mandelic acid, naphthenic acid, nicotinic acid, p-7/benzoic acid, glycine , monobutyl glutamate, phthalic acid, azelaic acid, vanillic acid monoester and diester each 1i each organic solvent 50T
Suspend in ILl, add 0.06P each of iodine, and add 7
The mixture was heated and reacted at 0° C. for 7 hours with stirring.

After cooling, 30 mA' of hexane was added to each, and after stirring, the organic solvent was washed with a 1% aqueous sodium thiosulfate solution, further washed with water, and concentrated under reduced pressure at 40° C. or lower to obtain a crystalline residue.

This crystal residue stand 0.5 f? 30 mL of a 2N saline ethanol solution was added to the solution, and the mixture was heated under reflux for 6 hours for saponification and decomposition. The solution was poured into water, and then extracted with hexane.

The generated potassium ferulate was removed to an aqueous layer, the hexane layer was dehydrated and dried, the hexane was concentrated under reduced pressure, and the obtained crystals were dried.

Each crystal was dissolved in hexane, and the components were analyzed by gas chromatography. Table 3 shows the results and the rearrangement rate (g) from 24-methylenecycloartanol organic acid ester to cyclobranol.

Example 38 A product obtained by deoxidizing 100 parts of degummed and descrewed rice bran oil with an acid value of 30.4 with a 10% caustic soda aqueous solution in the presence of 100 parts of a 50% ethanol aqueous solution and 300 parts of hexane. Concentrated dried mulberry of an aqueous oryzanol-containing alcohol solution (Oryzanol content was 56%, this oryzanol contained 44% of 24-methylenecycloartanol ferulic acid ester, and the content of cyclobranol ferulic acid ester was 1%) Collect 5g into a flask, add 20ml of toluene and 20ml of chlorobenzene, :!
: Add 30r/Ll of nitrobenzene, and add 0.0ml of iodine to this.
021 and sodium iodide 0. IP and barium iodide 0
．． IP was added, and the mixture was heated and reacted at 80 to 90°C for 5 hours while stirring.

After the reaction was completed, the mixture was extracted and purified by a conventional method to obtain 1.72 m crystals of mixed ferulic acid ester of sterine and triterpene alcohol containing 22% of cyclobranol ferulic acid ester.

The rearrangement rate from 24-methylene cycloartanol ferulate ester to cyclobranol ferulate ester was 47.7%, and the ferulate mixture of stellate triterpene alcohol containing 22% of this cyclobranol ferulate ester Crystal 11 was recrystallized by a conventional method to obtain 0.25 f? I got it.

Example 39 Wheat germ dark oil (oryzanol content 15%, 24-methylenecycloartanol ferulate ester content in this oryzanol 40%, cyclobranol ferulate ester content 0) was converted into methyl ester by a conventional method. 7.5 f of the residue concentrate (oryzanol content 25%) obtained by distilling most of the fatty acid methyls off was suspended in 20 m of chloroform and 3 Qm of nitromethane, and to this was added 0.03 P of iodine, 0.03 P of tetramethylammonium iodide, iy was added, and the mixture was heated and reacted at 60° C. for 5 hours while stirring.

After completion of the reaction, extraction and purification by conventional methods yields mixed crystals of ferulic acid esters of sterine and triterpene alcohols containing 21% of cyclobranol ferulic acid ester and 18% of 24-methylenecycloartanol ferulic acid ester. I got it.

The rearrangement rate from 24-methylene cycloartanol ferulate ester to cyclobranol ferulate ester was 52.5%.

Example 40 Rice bran dark oil (17% oryzanol content, 38% content of 24-methylenecycloartanol ferulic acid ester in this oryzanol, 2% content of cyclobranol ferulic acid ester) 105' in hexane 30
TLl and 3Qm of methyl-n-butyl ketone were suspended, and 0.07% of iodine was added to this. was added and reacted by heating at 65°C for 10 hours.

After the reaction is completed, extraction and purification are performed using conventional methods to obtain 1.1 ft of mixed crystals of ferulic acid ester of sterine and triterpene alcohol containing 19% of cyclobranol ferulic acid ester and 21% of 24-methylenecycloartanol ferulic acid ester. I got it.

The rearrangement rate from 24-methylene cycloartanol ferulate ester to cyclobranol ferulate ester was 44%.

This cyclobranol ferulic acid ester 19% and 24%
-Methylene cycloartanol ferulic acid ester 21
Other components of the crystal containing % are campesterol ferulate ester 4%, cycloartanol ferulate ester 3%, and cycloartenol ferulate ester 43%.
%Met.

This mixed crystal 0.8? By repeating recrystallization using a conventional method, 88% cyclobranol ferulic acid ester and 2
4-methylenecycloartanol ferulate ester 1
0.12r of crystals containing 2% were obtained.

Example 41 While thoroughly stirring rice bran oil foots, the pH was adjusted to 7.5 with caustic soda and sulfuric acid. Contains 1% norferulic acid ester) 5? 10r/Ll of hexane and 201'fl of methylisoamylketone
0.03Si' of iodine and 0.1?1 of calcium iodide. , dimethylaniline hydride iodide 0.1ti? was added, and the mixture was heated and reacted at 65°C for 8 hours with stirring.

After completion of the reaction, extraction and purification by conventional methods yields 12% campesterol, 1% stigmasterol, 3% β-sitosterol, 4% cycloartanol, 38% cycloartenol, 22% 24-methylenecycloalknol. , 0.41 of a mixture of each ferulic acid ester with 20% of cyclobranol was obtained.

The rearrangement rate from 24-methylene cycloartanol ferulic acid ester to cyclobranol ferulic acid ester was 48.5%.

Example 42 The residue obtained by methyl esterifying dark oil of rice bran using a conventional method and removing the fatty acid content by distillation (oryzanol content: 4
(24-methylene cycloartanol ferulic acid ester 42% contained in this oryzanol) was suspended in a mixed solvent of xylene 10TfLl and nitroethane 207rLl, and iodine 0.05f and aniline hydride iodide 0.41f were suspended in a mixed solvent of xylene 10TfLl and nitroethane 207rLl. The mixture was added and reacted while stirring at 80° C. for 5 hours.

After completion of the reaction, the mixture was extracted and purified by conventional methods to obtain 1.21 mixed crystals of ferulic acid ester of sterol and triterpene alcohol containing 23% of cyclobranol ferulic acid ester.

The rearrangement rate from 24-methylene cycloartanol ferulate to cyclobranol ferulate was 54.7%.

Example 43 Dark oil of rice germ (oryzanol content 22%, this oryzanol contains 39% 24-methylene-cycloartanol ferulic acid ester, 1% cyclobranol ferulic acid ester) 5y was mixed with 2 or ILl of heptane and 10rLl of benzene. Suspended in a solvent and added 0.07 iodine to it.
? and 0.32 ammonium iodide and heated at 70°C for 5 hours.
The reaction was carried out by heating while stirring.

After the reaction is completed, extraction and purification are carried out using conventional methods to obtain 0.6f mixed crystals of notriterpene alcohol and sterol ferulate containing 21% cyclobranol ferulate. I got it.

Example 44 24-methylenecycloartanol ferulic acid ester 2r,:! =24-methylenecycloartanol butyrate 2? Suspend the mixture in 60rIL of benzene,
Add 0.155' of iodine to this and heat to 80°C while stirring.
The mixture was heated and reacted for 6 hours.

After completion of the reaction, treatment by column chromatography and gas chromatography revealed that the reaction products were 28% cyclobranol ferulate, 22% 24-methylenecycloartanol ferulate, 24% cyclobranol butyrate, and A composition 3.81 containing 26% of 24-methylenecycloartanol butyrate was obtained.

Example 45 Campesterol ferulate ester 3%.

24-methylenecycloartanol acetate 97%
A mixture 2i consisting of
j' was added, and the mixture was heated and reacted at 700C for 4 hours.

After the reaction was completed, the reaction product was treated with column chromatography. The reaction product had a composition of 1.82 consisting of 3% campesterol ferulate, 47% 24-methylenecycloartanol acetate, and 50% cyclobranol acetate. Obtained.

Example 46 10% cycloartenol benzoate, 10% cycloartanol benzoate.

24-methylenecycloartanol benzoic acid ester 4
0%, 24-methylenecycloartanol palmitate 20% mixture 1? suspended in a mixed solvent of 20 yds of trichlorethylene and 40 yds of tonitromethane,
To this was added 0.05y of iodine, and the mixture was heated and reacted at 80°C for 5 hours.

After the reaction was completed, treatment with column chromatography and gas chromatography revealed that 10% cycloartenol benzoate, 10% cycloartanol benzoate, 18% 24-methylenecycloartanol benzoate, and cyclobranol benzoate. A composition 0.92 was obtained containing 22% acid diester, 12% 24-methylenecycloartanol palmitate, and 8% cyclobranol palmitate.

Examples 47 to 53 24-methylenecycloartanol baelatorum acid ester (Example 47), cinnamic acid (Example 48) 1, allocinnamic acid (Example 49), coumaric acid (Example 50), benzoyl acetic acid (Example 47)
51), α-naphthalic acid (52), and ferulic acid (53) @Hj' in hexane 10Tr
It was suspended in a mixed solvent of L1 and isopropyl acetate (101 nl), 0.055' of iodine was added thereto, and the reaction was heated at 70°C for 5 hours. Table 4 shows the measurement results and the rearrangement rate (c) from 24-methylenecycloartanol organic acid ester to cyclobranol organic acid.

Claims (1)

[Claims] A cyclobranol organic acid ester is produced by heating and reacting a substance containing 124-methylenecycloartanol organic acid ester or 24-methylenecycloartanol organic acid ester in the presence of iodine or iodine and iodide. 1. A method for producing a cyclobranol organic acid ester, which comprises isomerizing it into a cyclobranol organic acid ester. 2) Claim 1 which is IJium, potassium iodide, ammonium iodide, calcium iodide, barium iodide, tetramethylammonium iodide, dimethylaniline hydride iodide, aniline hydride iodide The method described in section. The 324-methylenecycloartanol organic acid ester contains at least one type of 24-methylenecycloartanol organic acid ester and an organic acid ester of campesterol, stigmasterol, β-sitosterol, cycloartanol, and cyfroatenol. The method according to claim 1, which is a mixture with the above. 424-methylene cycloartanol ferulic acid ester content is rice bran oil, rice germ oil, wheat germ oil foots, dark oils thereof, distillation residues of these dark oils, or solvent-treated oils thereof. Range 1
The method described in section. The organic acids of 524-methylenecycloartanol organic acid ester include acetic acid, butyric acid, isobutyric acid, methylethyl acetate, palmitic acid, monobutyl succinate, monomethyl adipate, azelaic acid, α-ketoglutaric acid, citric acid, benzoic acid, and ethoxy Benzoic acid, vanillic acid, isobanilic acid, phthalic acid, monoethyl phthalate, phenylacetic acid, hydrocinnamic acid, cinnamic acid, allocinnamic acid, coumaric acid, mantelic acid, ferulic acid, benzoylacetic acid, α-naphthalic acid, naphthenic acid, 4. The method according to claim 1 or 3, which is nicotinic acid, p-aminobenzoic acid, glycine, or monobutyl glutamate. 6. The method according to claim 2, 3, or 5, wherein the reaction temperature is 46 to 110°C. Claim 4, wherein the γ reaction temperature is 60 to 90°C.
The method described in section. 8 Reaction solvent: hexane, heptane, benzene, toluene, xylene, cyclohexane, ethylbenzene, isopropyl ether, n-butyl ether, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl n
-butyl ketone, methyl isoamyl ketone, cellosolve, butyl cellosolve, dioxane, ethyl acetate, isopropyl acetate, n-butyl acetate, butyric acid, nitromethane, nitroethane, nitrobenzene, chloroform,
J element, trichlorethylene, dichloroethyl ether,
The method according to claim 6 or 1, wherein at least one of ethylene dichloride, monochlorobenzene, bromopropylene, ethylene dibromide, and carbon disulfide is used.