JPH02240045A - Method for separating optically active 4-hydroxy-2-cyclopentenones - Google Patents

Abstract

PURPOSE:To readily separate and obtain the subject compounds which are intermediates for medicines and agricultural chemicals by subjecting a mixture containing optically active 4-hydroxyl-2-cyclopentenones and optically active 2-cyclopentenone esters to crystallizing treatment using a specific solvent. CONSTITUTION:A mixture containing optically active 4-hydroxy-2- cyclopentenones expressed by formula I (R' is H or lower alkyl; n is 4-8; mark *indicates asymmetric carbon atom) and optically active 2-cyclopentenone esters expressed by formula II (R'' is lower alkyl) is subjected to crystallizing treatment in a mixed solvent of a water-soluble organic solvent and water at a temperature >=10 deg.C below the melting point of the esters expressed by formula II which are to be crystallized. Thereby, the compounds expressed by formula II are crystallized and separated to afford the objective compounds expressed by formula I from the residual liquid part. Methanol, acetone, etc., are used as the above-mentioned organic solvent in an amount within the range of 0.5-2 weight ratio based on water. The total amount of the organic solvent and water is preferably 1-10 times based on the raw material mixture.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for separating optically active 4-hydroxy-2-cyclopentenones useful as pharmaceutical or agricultural intermediates.

(In the formula, R' represents a hydrogen atom or a lower alkyl group, n represents an integer of 4 to 8, and * represents an asymmetric carbon atom.) Optically active 4-hydroxy-2-cyclopene represented by Tenones are d1-cyclopentyone esters represented by the general formula (in the formula, R' represents a lower alkyl group, and R' and n have the same meanings as above), and the ester is hydrated. General formula (It) is provided as an asymmetric hydrolysis residue by asymmetric hydrolysis using an esterase having the ability to decompose the compound.

<Means for Solving the Problems> The present invention provides an optically active compound represented by the general formula (1) U (wherein, R'', R', n and this mark have the same meanings as above). 2-cyclopentenone esters are also produced at the same time, and column chromatography is generally used to separate and purify the two.

However, this method requires a large amount of solvent. Optically active 4-hydroxy-2-cyclopentenones and the following general formula (n) <Problem to be solved by the invention> The present invention overcomes the above problems and provides compounds represented by the general formula (1) above. An industrially advantageous separation method for optically active 4-hydroxy-2-cyclopentenones (wherein R' represents a lower alkyl group, and R', n and * have the same meanings as above). 2-cyclopentyone esters (n) are crystallized by crystallizing a mixture containing optically active 2-cyclopentenone esters shown in a mixed solvent of a water-soluble organic solvent and water. 11L, 4 from residual liquid part
-A method for separating 4-hydroxy-2-cyclopentenones (1) characterized by recovering hydroxy-2-cyclopentenones (1).

Examples of water-soluble organic solvents used in the present invention include alcohols such as methanol, ethanol, n-propyl alcohol, and isobropyl alcohol;
Examples include ketones such as acetone, ethers such as tetrahydrofuran or dioxane, and alcohols are preferred.

The ratio of these water-soluble organic solvents to water is 2
- Crystallization temperature of cyclopentyone ester (II), water-soluble organic solvent or water solubility of the ester (6) and 4-hydroxy-2-cyclopentenone (I), water-soluble organic solvent It is determined appropriately depending on the total amount of solvent and water, but usually the weight ratio is 0.25 to 1.
It is in the range of 0, preferably in the range of 0.6 to 2.

In addition, the total amount of water-soluble organic solvent and water is determined by the ratio of water-soluble organic solvent and water, the crystallization temperature of 2-cyclopentyone ester (seaweed), and the ester II (10 and 4
-Hydroxy-2-cyclopentenones (1) are appropriately determined depending on the water-soluble organic solvent or the solubility in water, but usually the above-mentioned esters) and 4-hydroxy-2-cyclopentenones (!) ) for a mixture of
~20 times by weight, preferably 1 to 10 times by weight.

As for the crystallization method of the above esters φ), the above esters (H) are added to a mixed solvent of water-soluble organic solvent and water.
and 4-hydroxy-2-cyclopentenones 0) with heating if necessary, and then crystallize. ■Dissolve the above mixture in a water-soluble organic solvent and crystallize at the dissolution temperature. Add the required amount of water to crystallize. ■Dissolve the above mixture in a water-soluble organic solvent while heating, and add water at the crystallization temperature of the above ester (n) in the mixed solvent. 1 method of crystallization is applied.

The crystallization temperature is not particularly limited, but a temperature that is usually 10°C or more lower than the melting point of the above-mentioned esters (shun) is preferred.

During crystallization, seed crystals of the ester (II) can be inoculated if necessary.

After the crystallization of the ester (n), the ester (n) can be separated as crystals by, for example, a transient operation, and 4-hydroxy-2-cyclopentenone is extracted from the residual liquid after crystal separation. Recovery of type (1) can be carried out, for example, by adding a large amount of water to the mixed solvent or by distilling off a water-soluble organic solvent and adding methyl isobutyl ketone, toluene, ethyl acetate, or ethyl ether to the residue. This is carried out by adding a solvent to perform extraction, and then distilling off these solvents from the organic layer.

The recovered 4-hydroxy-2-cyclopentenones (1
) can be recrystallized using organic solvents such as aromatic hydrocarbons such as benzene, toluene, xylene or chlorobenzene,
Ester systems such as methyl acetate or ethyl acetate, ether systems such as isoprobyl ether or butel ether, halogenated hydrocarbon systems such as dichloromethane, dichloroethane or chloroform, ketone systems such as acetone, methyl ethyl ketone or methyl isobutyl ketone,
The reaction is carried out in an alcohol-based solvent such as isobrobyl alcohol, or an aliphatic hydrocarbon-based solvent such as hexane, hebutane, petroleum ether, or polygloin, alone or in a mixture thereof.

The use of these organic solvents is not particularly limited, but is usually in a range of 1 to 20 Mm times the amount of 4-hydroxy-2-cyclopentenones (I).

The temperature during recrystallization is not particularly limited and is appropriately set depending on the type and amount of solvent used, but is usually about io'c lower than the melting point of 4-hydroxy-2-cyclopentenones (1). It's temperature.

Examples of the recrystallization method include the same method as the crystallization method for ester (II).

During recrystallization, 4-hydroxy-2-cyclopentenones (1)
Seed crystals can also be inoculated.

Moreover, the recrystallization operation can be repeated as necessary.

4-Hydroxy from the mixture after recrystallization
The 2-cyclopentenones (1) are removed, for example, by filtration.

A mixture of 4-hydroxy-2-cyclopentenone (lm<1) and esters has the general formula (auto)O (wherein, R' is a hydrogen atom or a lower alkyl group, R'
represents a lower alkyl group, and n represents an integer of 4 to 8. ) The d1-cyclopentenone esters represented by the following can be produced by asymmetrically hydrolyzing any one of the optically active forms of the esters using an esterase capable of hydrolyzing esters.

The above-mentioned noesterase may be produced by a microorganism or may be derived from an animal or plant.

In addition, esterase means esterase in a broad sense including lipase.

Specific examples of microorganisms that produce esterases include Enterobacter, Arthrobacter, Previbacterium, Pseudomonas, Alcaligenes, Micrococcus, Chromobacterium, Microbacterium, Corynebacterium, Bacillus, Lactobacillus, Trichoderma 1 Candida, Saccharomyces, Rhodotorula, Krybutco, Kas,
Microorganisms belonging to the genus Torlobussis, Pichia, Penicillium, Aspergillus, Lisophus, Mucor, Aureobasidium, Actinomyces, Nocardia, Strebtomyces, Hansenula, and Achromobacter are exemplified. Ru.

The above-mentioned microorganisms are usually cultured according to conventional methods, and a culture solution can be obtained by, for example, liquid culture.

For example, a sterilized liquid medium [for molds and yeasts, malt extract-yeast extract medium (dissolve peptone 6P1゛glucose IOP, barley! extract 8P, and yeast extract 8t in 11 parts of water and adjust the pH to 6.5), bacteria 1ζ is a sweetened bouillon medium (glucose Vat. pebtone 6P, meat extract 5? and Na (J 8 P dissolved in water 11, $87).
2)] and cultured with reciprocating shaking at 20 to 40"C for 1 to 8 days,
Further, solid culture may be performed as necessary.

Furthermore, some of these esterases originating from microorganisms are commercially available and can be easily obtained. Specific examples of commercially available esterases include the following.

Shademonas lipase [Lipase P (Amano Pharmaceutical); Aspergillus lipase [Lipase AP (Amano Pharmaceutical)], Mucor lipase [Lipase M-AP]
(manufactured by Amano Pharmaceutical Co., Ltd.)], lipase of Candida Cylindrace [Li/f-ze MY (manufactured by Meito Sangyo Co., Ltd.)], lipase of the genus Alcaligenes [Lipase PL (manufactured by Meito Sangyo Co., Ltd.)], lipase of the genus Achromobacter [Lipase PL (manufactured by Meito Sangyo Co., Ltd.)] lipase ALI (manufactured by Meito Sangyo)], Arthrobacter paste Iase (manufactured by Shin Nippon Kagaku), lipase of Chromobacterium (manufactured by Toyo Jozo), lipase of Rhizopus delemer [Talipase (manufactured by Tanabe Seiyaku)] ], lipase of the genus Rhizobus [Rivase Saiken (Osaka Bacteria Research Institute)].

Further, examples of esterases derived from animals and plants include the following.

Steabsin, pancreatin, pig liver esterase, WlleatGerm esterase.

As the esterase used in this asymmetric hydrolysis reaction, enzymes obtained from animals, plants, and microorganisms are used.
It can be used in various forms as needed, including purified enzymes, crude enzymes, enzyme-containing products, microbial culture fluids, cultures, bacterial cells, cultured oral fluids, and processed products. Enzymes and microorganisms can also be used in combination.

Alternatively, it is also possible to use an immobilized enzyme immobilized on a resin or the like, or as an immobilized bacterial cell.In the asymmetric hydrolysis reaction, a mixture of raw material esters and the above enzymes or microorganisms is usually prepared in a buffer solution. This is done by stirring vigorously.

As the buffer, commonly used buffers of inorganic acid salts such as sodium phosphate and potassium phosphate, buffers of organic acid salts such as sodium acetate and sodium citrate, etc. The pH is preferably 8 to 11 for a culture solution of a microorganism that is not alkaliphilic or an alkaline esterase, and the pH is preferably 5 to 8 for a culture solution of a microorganism that is not alkaliphilic or an esterase that does not have alkali resistance. Concentration is usually 0.05~
2M, preferably 0.06-0. It is in the range of 5M.

The reaction temperature is usually 10 to 60°C, and the reaction time is generally 10 to 70 hours, but is not limited thereto.

After the completion of such asymmetric hydrolysis reaction, 4-hydroxy-
2-Cyclopentenones (I) and 2-cyclopentenone esters (II) can be extracted from the organic layer by extracting the hydrolysis reaction solution with a solvent such as methyl isobutyl ketone, ethyl acetate, or ethyl ether. This is done by distilling off the solvent.

The raw material ester (self) is represented by the general formula (ff)c, R/
and n have the same meanings as above. ) is produced by reacting 8-hydroxy-4-cyclopentenones represented by ζ with lower aliphatic carboxylic acids, their acid anhydrides, and their metal salts to simultaneously perform acylation and rearrangement reactions. ζ can be done.

Examples of lower aliphatic carboxylic acids include acetic acid, propionic acid,
Butyric acid, valeric acid, chloroacetic acid, dichloroacetic acid, bromoacetic acid, etc., and their metal salts include lithium salts, sodium salts, potassium salts, calcium salts, copper salts, zinc salts, palladium salts, and lead salts of these lower aliphatic carboxylic acids. Examples include salt, tin salt, manganese salt, and cobalt salt. In this reaction, 8-hydroxy-4-cyclopentenones<E
The amount of the lower aliphatic carboxylic acid used is usually 1 equivalent or more, and the amount of the metal salt used is usually 0.01 to 5 equivalents or more, preferably 0.01 to 0.6 times the amount of V). Also,
The amount of the aliphatic carboxylic acid anhydride used is 1 equivalent or more relative to the raw material cyclopentenone (ff).

In this reaction, it is very important to use the above-mentioned lower aliphatic carboxylic acid, its metal salt, and its acid anhydride, and there is no method that is effective even if any of these components is omitted. Therefore, both the rearrangement reaction and the acylation do not proceed sufficiently at the same time.

When a solvent is used in this reaction, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, dimethyl sulfoxide, hexane, etc. Examples include a single solvent or a mixture of solvents inert to the reaction, and the amount used is not particularly limited. Moreover, lower aliphatic carboxylic acids can also be used as a solvent.

The reaction temperature is usually 0 to 150°C, preferably 80 to 140°C.

Although the reaction time is not particularly limited, it is usually 0.5 to 10 hours. As the reaction time increases, the generated general formula (self)
Since the dj-cyclopentenone ester represented by dj-cyclopentenone ester is partially decomposed, unnecessary length of time is not preferable.

As a reaction method, for example, (1) 8-hydroxy-4-cyclopentenone represented by the general formula (Iv), a lower aliphatic carboxylic acid, its acid anhydride, and its metal salt are simultaneously charged into a reaction vessel and reacted. ■ A lower aliphatic carboxylic acid and its acid anhydride are added to the 8-hydroxy-4-cyclopentenone represented by the general formula (y) and reacted for a certain period of time (usually 0.1 to 6 hours). Examples include a method of adding a metal salt of a lower aliphatic carboxylic acid and further reacting.

In this way, 8-hydroxy-4-cyclopentenones represented by general formula (IV) and d1-cyclopentenone esters represented by general formula (2) can be obtained. Cyclopentenones (IT) can be produced by a known method of rearranging furancarbinols represented by the general formula 0E (wherein R' and n have the same meanings as above).

<Effects of the Invention> According to the present invention, optically active 4 represented by general formula (1)
-Hydroxy-2-cyclopentenones can be efficiently and industrially advantageously separated.

<Example> The present invention will be explained below using examples.

Reference example 1 6? of sodium acetate was dissolved in 4560P water, and acetic acid was added to adjust the pa to 4.2.

This I! Add 2-(1-hydroxy-7-methoxycarbonylheptyl)-furan l14? to the aqueous solution and continue a# at 100''C under a nitrogen stream until the raw material is used up.

After the reaction was completed, the reaction mixture was cooled, extracted twice with 500 t# of methyl isobutyl ketone, and the liquid was separated.
Methyl isobuterketone was distilled off from a to give 8-hydroxy-2-(6-methoxycarbonylhexyl)-4-cyclopentenone and 4-hydroxy-2-(G-methoxycarbonylhexyl)-2-cyclo 92 as a mixture of bentenone? (yield 80.7%).

The above mixture 480? Acetic acid 68.0? , anhydrous vinegar U? 2
0. Add 4 F and 1.21 g of anhydrous sodium acetate and heat at 120° C. for 4 hours. The reaction solution was checked by gas chromatography to confirm that no reaction raw material was detected in the reaction solution, and the reaction was completed. The reaction solution was concentrated under reduced pressure, and 8 toluene was added to the concentrated residue.
00* and then rinse with water. The obtained organic layer was dried over anhydrous magnesium sulfate and then reduced by 1k to obtain 4-acetoxy 2-(6-methoxycarbonylhexyl)-2-cyclopentenone 55.2F (yield 98%).

bp. 180 to 185°C/0.6flHP Reference Example 2 8-Hydroxy-2-(6-methoxycarbonylhexyl)-4-cyclopentenone and 4-
Hydroxy-2-(6-methoxycarbonylhexyl)
-2-Cyclopentenone mixture 24z1 Brobionic acid 86P1 A mixture of brobionic anhydride 811 and propionate sodium 1.6 l was reacted at 120 to 126°C for 5 hours.

The reaction mixture was concentrated under reduced pressure, and the resulting residue was added with 200 g of water.
After adding 7, the mixture was extracted with a tornado 400d. The organic layer was washed with 8% sodium bicarbonate solution and water in that order.

Thereafter, 28.4-probionyloxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone was treated in the same manner as in Reference Example 1. IP (yield 96%) was obtained.

Example 1 d1-4-acetoxy 2-(6-
methoxycarbonylhexyl)-2-cyclopentenone 40F, 0.8 molar phosphate buffer (pH 7.5)
) i and Shademonas lipase (Amanolipase rJ) 4P was vigorously stirred at 40°C for 7 hours. The organic skin obtained by extracting the reaction mixture with toluene was concentrated under reduced pressure. A residue of iL was obtained. This residue 10? A mixture of 80 P of methanol and 40 P of water was stirred at 40°C for about 80 minutes, then cooled and kept at 0-5°C for 2 hours.

After separating the precipitated crystals, the P solution was concentrated under reduced pressure to distill off methanol. 80g of methyl isobutyl ketone from the residue
2. The organic layer obtained by extraction with j was concentrated under reduced pressure.
A concentrated residue of 6 4 P was obtained.

Toluene 16 in this residue? and hebutane 9P and stirred at 40°C for about 80 minutes, cooled and heated to 20°C for 4R.
Approximately 100 crystals of (t)monohydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone were inoculated and cooled to 6°C. It was kept at θ~5°C for 2 hours.

The precipitated crystals were filtered with P and dried to give 4R(-!-}-hydroxy-2-(6-methoxycarbonylhexyl)-2
-Cyclopentenone 1.915' in Example 2 Residue 8 obtained after completion of the asymmetric hydrolysis reaction in Example 1
9. 10 out of 8 points? A mixture of , isobrobyl alcohol 21 and water 85F was stirred at 40°C for about 80 minutes, then cooled and kept at 0 to 6°C for 2 hours. After separating the precipitated crystals, the P solution was concentrated under reduced pressure to remove isopropyl alcohol, and the resulting residue was mixed with 80% ethyl acetate. Extracted with. The organic layer was concentrated under reduced pressure to distill off about 24 P of ethyl acetate. About 866 P of the obtained ethyl acetate solution was added with 6? of n-hexane. was added, stirred at 85°C for 1 hour, and then cooled.

Approximately iooq of crystals of 4R(di)-hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone were softened at 25°C and cooled to 6°C. 2 to 8-6°C
Saved time. After passing through the precipitated crystals, they were dried and subjected to 4R (→
-Hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone 1.87F was obtained.

[4] +16.8° (C=1, methanol), m
p. 60.0-60.5°C Reference Example 8 2F sodium acetate was dissolved in 1500F water, and acetic acid was added to adjust the pH to 4. Adjusted to 1S.

Add 80% of 2-(1-hydroxy-7-ethoxycarbonylbutyl)-furan to this aqueous buffer solution. and continue stirring at 100°C under a nitrogen stream until all the raw materials are used up.

8-hydroxy-2-(6-ethoxycarbonylhexyl)-4-cyclopentenone and 4-hydroxy-2-(6-ethoxycarbonylhexyl) )-24.6F was obtained as a mixture of cyclopentenone (yield: 82%).

Above mixture 1 2. 7 P and acetic acid 40? , acetic anhydride 6
．． Add IP and sodium acetate 241y-, 110
Heat at ℃ for 4 hours.

After completion of the reaction, post-treatment was performed according to Reference Example 1 to obtain 4-acetoxy-2-(6-ethoxycarbonylhexyl)-2-
Cyclopentenone 14.9P (yield 96.1%) was obtained.

bp. 189 to 198°C/0, 5ggHP Example 8 4-acetoxy 2-(6-ethoxycarbonylhexyl)-2-cyclopentenone obtained in Reference Example 8 44,0.
8 molar phosphate bag 7y-(pH 7.5) 100d;
td and Schaetomonas lipase (Amano lipase r
The mixture of PJ)0,4F was vigorously stirred at 25-80°C for 10 hours. The reaction mixture was extracted with toluene, and the resulting organic layer was concentrated under reduced pressure to give 8.88? A residual liquid was obtained.

Add this residue to acetone 19.5? 19.54 ml of water was added at 86°C.

Thereafter, it was cooled and kept at 0-6°C for 2 hours.

After separating the precipitated crystals from P, the furnace solution was concentrated under reduced pressure to distill off acetone. The residue was extracted with 40 ml of toluene, and the resulting organic layer was concentrated under reduced pressure. A concentrated residue of 21 was obtained.

6F of isobrobyl ether and 2.4F of petroleum ether were added to this concentrated residue, stirred at 40°C for about 80 minutes, cooled, and heated to 25°C to form 4R(→monohydroxy-2-(6-methoxycarbonylhexyl)- Approximately to'II9 crystals of 2-cyclopentenone were inoculated, cooled to 5°C, and then kept at 6°C for 2 hours.The precipitated crystals were filtered and dried to give 4R(t)-hydroxy-2- 0.8P of (6-methoxycarbonylhexyl)-2-cyclopentenone was obtained.
mp-4 9.0-4 9.6°C Example 4 4-probionyloxy-2-(6-methoxycarbonylhexyl)-2-cyclopentynone 6 obtained in Reference Example 2
F. 0.8 molar phosphate buffer (pH 6.0) 1
A mixture of 0.00g and Arthrobacter lipase (manufactured by Shin Nihon Kagaku) 0.8P was vigorously stirred at 80 to 85°C for 10 hours. 4. The reaction mixture was extracted with methyl isobutyl ketone, and the resulting organic layer was concentrated under reduced pressure. 9 2
A residue of F was obtained. This residue was dioxane 20? Dissolve in water at 85°C to 80% water. added. After that, cool it down to 0~
It was kept at 6°C for 2 hours. After separating the precipitated crystals from P, the P solution was concentrated under reduced pressure. Water and methyl isobutyl ketone were added to the residue for extraction, and the resulting organic layer was concentrated under reduced pressure.

Xylene 105' and hebutane 7 are added to the obtained concentrated residue.
After adding P and stirring at 40°C for about 80 minutes, it was cooled and heated to 20°C.
About 10 capes of crystals of 4113-hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone were inoculated at 4113-hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone, cooled to 4°C and then kept at 0-6°C for 2 hours. After passing through the precipitated crystals, they were dried to form 4R(-l-
1-hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone 0.84F was obtained. [α North 0+16.2° (C=1, methanol), mL 6
0.0~6 0.5°C Reference Example 4 8. IP Phosphorus Wli Hydrogen Potassium 4160? of water, and the pH was adjusted to 4.2 by adding phosphoric acid. Add 106 cm of 2-(1-hydroxy-7-methoxycarbonylpentyl)-furan to this aqueous solution, and continue stirring at 100° C. under a nitrogen stream until the raw material is exhausted.

After the reaction was completed, the reaction mixture was cooled, extracted twice with 600 ml of methyl isobutyl ketone and separated, and methyl isobuter ketone was distilled off from the resulting organic layer to give 8-hydroxy-2- (6-methoxycarbonylbutyl)-4
-cyclopentenone and 4-hydroxy-2-(6-
(methoxycarbonylbuter)-2-cyclopentenone as a mixture 84, 8? (yield 79.6%).

The above mixture 58. Acetic acid in OF 86.5P1 Acetic anhydride 26
．． Add 6P and 1.71 g of potassium acetate and heat at 120° C. for 4 hours.

Following the post-treatment according to Reference Example 1, 4-acetoxy 2-
(4-methoxycarbonylbutyl)-2-cyclopentynone 59.7P (yield 94%) was obtained.

Example 6 4-acetoxy 2-(4-methoxycarbonylbutyl)-2-cyclopentenone 8P, 0.8 obtained in Reference Example 4
Molar phosphate buffer (pH 7.5) too- and Pseudomonas lipase (Amanolipase rPJ)
) The 0.8F mixture is stirred vigorously at 26-80C for 10 hours. The reaction mixture was extracted with toluene, and the resulting organic layer was concentrated under reduced pressure to give 7.6? A residue was obtained. 20 methanol in this residue? Then add 25F of water and stir at 86°C for about 80 minutes.

Thereafter, it is cooled and kept at 5°C for 8 hours. The precipitated crystals are P
After separation, the P solution is concentrated under reduced pressure to distill off methanol.

The residue is extracted with ethyl acetate, and the resulting organic layer is concentrated under reduced pressure.

Acetone (15F) and hexane (1) were added to the resulting concentrated residue.
2? was added and stirred at 86°C for 1 hour, then cooled and
Keep at ℃ for 2 hours. If the precipitated crystals are passed through and dried, 4
R(t)monohydroxy-2-(4-methoxycarbonylbuter)-2-cyclopentenone is obtained.

(Margin below)

Claims (4)

[Claims] (1) The following general formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) The optically active 4-hydroxy-2-cyclopentenones represented by the following general formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, R″ represents a lower alkyl group, and R', n, and * represent the same meanings as above.) A mixture containing an optically active 2-cyclopentenone ester represented by 2-Cyclopentenone esters (II) are crystallized and separated from the mixed solvent by crystallization treatment, and 4-hydroxy-2
-4-hydroxy-2-cyclopentenones (I) characterized by recovering cyclopentenones (I)
separation method. (2) 4-hydroxy-2-cyclopentenones (I
2. The method according to claim 1, wherein upon recovery of the compound, a recrystallization treatment is performed from an organic solvent. (3) General formula (III) below ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (III) (In the formula, R' is a hydrogen atom or a lower alkyl group, R''
represents a lower alkyl group, and n represents an integer of 4 to 8, respectively. ) The dl-cyclopentenone esters represented by the general formula (I) are obtained by asymmetrically hydrolyzing either one of the optically active forms of the esters using an esterase having the ability to hydrolyze the esters. 3. The method according to claim 1, wherein a mixture containing optically active 4-hydroxy-2-cyclopentenones represented by formula (II) and optically active 2-cyclopentenone esters represented by general formula (II) is obtained. (4) The method according to any one of claims 1, 2, or 3, wherein the water-soluble organic solvent is an alcohol.