JPH0729971B2 - Process for producing optically active 4-hydroxycyclopentenones - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention is of the general formula (I)

[Chemical 3] (In the formula, R represents an alkyl group, an alkenyl group or an alkynyl group.) The present invention relates to a novel method for producing optically active 4-hydroxycyclopentenones.

BACKGROUND OF THE INVENTION Optically active 4-hydroxycyclopentenones represented by the above general formula (I) are useful as intermediates for agricultural chemicals, fragrances or pharmaceuticals, for example, prostaglandin. It can be used as an important intermediate of a derivative. Furthermore, these optically active compounds are converted into sulfonic acid esters with, for example, paratoluenesulfonic acid or methanesulfonic acid, and then reacted with a base, or with sodium acetate, sodium dichloroacetate, sodium trichloroacetate, or the like. The corresponding ester may be converted to a 4-hydroxycyclopentenone compound having a configuration opposite to the original coordination by hydrolysis. The optically active 4-type compound represented by the general formula (I)
Hydroxycyclopentenones can also be synthesized by asymmetric hydrolysis of acetate of dl-4-hydroxy-2-cyclopentenone with an enzyme or the like, but it is always satisfactory in terms of optical purity. Not going.

From the above, the present inventors have made the optically active 4-hydroxycyclopentenones represented by the general formula (I) inexpensive and industrially advantageous in high purity and high yield. As a result of research on the method of obtaining the present invention, the present invention has been completed.

That is, the present invention provides a compound represented by the general formula (IV)

[Chemical 4] (In the formula, R has the same meaning as described above, provided that the substituent R at the 2-position and the methyl group at the 3-position are in trans-coordination.)
Is a method for producing an optically active 4-hydroxycyclopentenone represented by the general formula (I), which comprises rearranging an optically active 4-cyclopentenone alcohol represented by

Here, the optically active 4-cyclopentenone alcohols represented by the general formula (IV) are represented by the general formula (III)

[Chemical 5] (In the formula, R has the same meaning as described above, R ₁ represents an acyloxyl group, provided that the substituent R at the 2-position and the substituent R _{1 at the} 3-position are in trans-coordination.) Dl-4-shown
It can be obtained by asymmetric hydrolysis of cyclopentenone esters using an enzyme or a microorganism.

Further, dl-4-represented by the general formula (III)
Cyclopentenone esters have the general formula (II)

[Chemical 6] (In the formula, R has the same meaning as described above, provided that the substituent R at the 2-position and the hydroxyl group at the 3-position are in the trans-coordination.) And dl-4-cyclopentenone alcohols and fats It can be obtained by reacting (esterifying) a group carboxylic acid.

The present invention will be described in detail below. 4-cyclopentenone esters represented by the general formula (III) are
By reacting the dl-4-cyclopentenone alcohol represented by the general formula (II) with the aliphatic carboxylic acid, it can be easily produced in a good yield.

Here, dl-4- used as a raw material
Cyclopentenone alcohols can be easily produced, for example, by rearranging furancarbinol as shown in the following formula, and the following compounds are exemplified as dl-4-cyclopentenone alcohols.

[Chemical 7] 3-hydroxy-2-methyl-4-cyclopentenone,
2-ethyl-3-hydroxy-4-cyclopentenone,
3-hydroxy-2-n-propyl-4-cyclopentenone, 2-isopropyl-3-hydroxy-4-cyclopentenone, 3-hydroxy-2-n-butyl-4-cyclopentenone, 2-isobutyl- 3-hydroxy-4
-Cyclopentenone, 3-hydroxy-2-n-pentyl-4-cyclopentenone, 2-isopentyl-3-hydroxy-4-cyclopentenone, 3-hydroxy-2
-N-hexyl-4-cyclopentenone, 3-hydroxy-2-n-heptyl-4-cyclopentenone, 2-allyl-3-hydroxy-4-cyclopentenone, 2-
(2-cis-butenyl) -3-hydroxy-4-cyclopentenone, 2- (ω-butenyl) -3-hydroxy-
4-cyclopentenone, 2- (2-cis-pentenyl)
-3-Hydroxy-4-cyclopentenone, 3-hydroxy-2- (2-trans-pentenyl) -4-cyclopentenone, 2- (3-cis-hexenyl) -3-hydroxy-4-cyclopentenone , 3-hydroxy-2-
Propargyl-4-cyclopentenone, 3-hydroxy-2- (2-pentynyl) -4-cyclopentenone, 3
-Hydroxy-2- (α-methylallyl) -4-cyclopentenone.

The aliphatic carboxylic acids as the other raw material include aliphatic carboxylic acid halides and aliphatic carboxylic acid anhydrides, and the following compounds are exemplified. Acetic acid chloride, acetic acid bromide, acetic anhydride, propionic acid chloride or bromide, propionic anhydride, butyryl chloride or bromide, caproyl chloride or bromide, caprylic acid chloride or bromide, caprynoyl chloride or bromide, dodecanoin chloride or bromide, palmitoyl Chloride or bromide, chloroacetyl chloride or bromide,
Dichloroacetyl chloride or bromide.

The reaction of such dl-4-cyclopentenone alcohols with an aliphatic carboxylic acid is carried out by applying a usual esterification condition, and reacting with a catalyst in the presence or absence of a solvent. To be done. 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, hexane and other aliphatic or aromatic hydrocarbons, ethers, halogenated hydrocarbons, etc. A mixture can be given. The amount used can be used without particular limitation. The amount of the aliphatic carboxylic acid used in the reaction is 1 equivalent or more with respect to the raw material dl-4-cyclopentenone alcohol, and the upper limit is not particularly limited, but it is preferably 1 to 4 equivalents. As a catalyst,
Examples thereof include organic or inorganic basic substances such as triethylamine, tri-n-butylamine, pyridine, picoline, sodium carbonate, sodium methylate and potassium hydrogencarbonate. The amount used is not particularly limited, but is usually 1 with respect to dl-4-cyclopentenone alcohols.
~ 5 equivalents. When an organic amine is used as a solvent, the amine may act as a catalyst. Further, acids such as toluene sulfonic acid, methane sulfonic acid and sulfuric acid can also be used as a catalyst. Reaction temperature is usually -20
℃ -150 ℃, preferably -10 ℃ -120 ℃
Is the range. The reaction time is not particularly limited. By such a reaction, dl-represented by the general formula (III)
4-Cyclopentenone esters can be obtained easily and in good yield, and they can be easily isolated from the reaction mixture by a conventional separation means such as extraction, liquid separation, concentration and distillation. The reaction mixture can proceed to the next step as it is.

The optically active 4-cyclopentenone alcohols represented by the general formula (IV) are microbial esterases or animal and plant esterases capable of hydrolyzing the 4-cyclopentenone esters represented by the general formula (III). Is used to hydrolyze one of the optically active forms of the esters.

The esterase-producing microorganism used in this reaction is not particularly limited as long as it is an esterase-producing microorganism having the ability to asymmetrically hydrolyze dl-4-cyclopentenone esters. (Esterase in the present invention means a broad sense esterase including lipase).

Specific examples of such microorganisms include microorganisms belonging to the following genera. Enterobacter, Arthrobacter, Brevibacterium, Pseudomonas, Alcaligenes, Micrococcus, Chromobacterium, Microbacterium, Corynebacterium, Bacillus, Lactobacillus, Trichoderma, Candida Genus, Saccharomyces, Rhodotorula, Cryptococcus, Tollopsis, Pichia, Penicillium, Aspergillus,
Microorganisms belonging to the genera Rhizopus, Mucor, Aureopasidium, Actinomucor, Nocardia, Streptomyces, Hansenula, and Achromobacter.

Examples of microorganisms belonging to each of these genera include the following. Rhodotorula minuta I
FO-0387, IFO-0412, Rhodotorula rubra IFO-0870, Rh
odotolura minuta var texensis IFO-0879, Trichoder
ma longibrachiatum IFO-4847, Candida krusei out-6
007, Candida cylindracea, Candida tropicalis PK
233, Candida utilus IFO-1086, Pseudomonas fragi
IFO-3458, Pseudomonas putida IFO-12996, Pseudomo
nas fluorescens IFO-3903, Pseudomonas aeruginosa
IFO-3080, Bacillus cereus IFO-3466, Bacillus sub
tilis ATCC-6638, Bacillus pulmilus IFO-12092, Ba
cillus subtilis var niger IFO-3108, Nocardia unif
ormis subtsuyanarenus ATCC-21806, Nocardia unifor
mis IFO-13072, Chromobacterium chocolatum IFO-375
8, Chromobacterium iodinum IFO-3558, Flavobacter
ium arbonescens IFO-3750, Flavobacterium heparinu
m IFO-12017, Rizopus chinensis IFO-4768, Mucor jav
anicus IFO-4572, Aspergillus niger ATCC-9642, Alc
aligenes faecalis IFO-12669, Torulopsiscandida IF
O-0768, Corynebacterium sepedonicum IFO-13763, S
accaromycesrouxii IFO-0505, Arthrobacter simplex I
FO-3530, Streptomyces grisens IFO-3356, Brevibac
terium ammoniagenes IFO-12072, Brevibacterium div
aricatum ATCC-14020, Micrococcus varians IFO-376
5, Micrococcus luteus IFO-3066, Enterobacter clo
acae IFO-3320, Conynebacterium ezui ATCC 7699, Lac
to bacillus casei IFO 3322, Cryptococcus albidus
IFO-0378, Pihia polimorpha IFO 1166, penicillium
frezuentans IFO 5692, Aureobasidium pullulans IF
O 4464, Actinomucor elegans IFO 4022, Hansenula an
omala var ciferrii out 6095, Hansenula anomala IF
O-0118, Achromobacter parvulus IFO-13181, Achromo
bacter sinplex IFO-12069. For the culture of the above-mentioned microorganisms, a liquid culture is usually obtained by performing liquid culture according to a conventional method. For example, a sterilized liquid medium [malt extract / yeast extract medium for molds and yeasts (peptone 5
g, glucose 10 g, malt extract 3 g, yeast extract 3
g to dissolve to pH 6.5), and for bacteria, add sugar to broth medium (dissolve 10 g of glucose, 5 g of peptone, 5 g of meat extract, and 3 g of Nacl in 1 liter of water to bring pH to 7.2)]. Usually, reciprocal shaking culture is performed at 20 to 40 ° C for 1 to 3 days. In addition, solid culture may be performed if necessary.

Some of these esterases originating from microorganisms are commercially available and can be easily obtained. Specific examples of commercially available esterases include:
For example: Pseudomonas lipase (manufactured by Amano Pharmaceuticals), Aspergillus lipase (lipase AP (manufactured by Amano Pharmaceuticals)), Mucor lipase M-Ap (manufactured by Amano Pharmaceuticals), lipase of Candida syrindasse (lipase MY (Meito Sangyo) )) Alcaligenes lipase (Lipase PL (Meito Sangyo)), Achromobacter lipase (Lipase AL)
(Manufactured by Meito Sangyo Co., Ltd.), lipase of Arthrobacter sp. , Rhizopus lipase (Lipase Saiken (Osaka Bacteria Research Institute)).

Animal / plant esterases can also be used. Specific examples of these esterases include the following. Steapsin, pancreatin, pig liver esterase, Wheat Germ esterase. Esterases (hydrolases) used in this reaction, and the forms of use of enzymes obtained from animals, plants and microorganisms include purified enzymes, crude enzymes, enzyme-containing substances, microbial culture liquids, cultures, cells, culture ports. It can be used in various forms such as a liquid and those obtained by treating them as needed, and an enzyme and a microorganism can also be used in combination. Alternatively, it can also be used as an immobilized enzyme or immobilized bacterium immobilized on a resin or the like. This hydrolysis reaction is dl-4-
It is usually carried out by vigorously stirring the cyclopentenone ester and the enzyme or microorganism in a buffer solution.

As the buffer solution, a commonly used buffer solution of an inorganic acid salt such as sodium phosphate and potassium phosphate,
A buffer solution of an organic acid salt such as sodium acetate or sodium citrate is used, and its pH is 8 to 11 for the culture solution of alkalophilic bacteria or alkaline esterase, and it does not have the alkali solution or the culture solution of non-alkalophilic microorganisms. For esterase, a pH of 5-8 is preferred. Concentration is normal
It is in the range of 0.05 to 2M, preferably 0.05 to 0.5M. 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 reaction is completed, in order to separate the hydrolysis product and the hydrolysis residue from the reaction solution, the hydrolysis solution is subjected to extraction treatment with a solvent such as methyl isobutyl ketone, ethyl acetate, ethyl ether, etc., and the solvent is distilled off from the organic layer. After the removal, the concentrated residue may be further distilled or treated by column chromatography to separate the optically active 4-cyclopentenone alcohols and the optically active 4-cyclopentenone esters from each other. The optically active 4-cyclopentenone esters recovered here can be further hydrolyzed and used as a raw material for producing a symmetric body.

The optically active 4-hydroxy-cyclopentenones represented by the general formula (I) are the optically active 4-cyclopentenone alcohols represented by the general formula (IV) obtained by the above-mentioned method. It is produced by rearrangement while maintaining the steric structure in the presence of a base or a catalyst.
Incidentally, no optically active 4-cyclopentenone alcohol represented by the general formula (IV), which is a raw material of this reaction step, has been known so far, and only Tetra as a dl-form is used.
hedron, Letter, No. 39, 3555-3558 (1976) (I)
It is described that they are a pair of.

[Chemical 8]

However, the specific description and separation of the pair (i) of the optically active substances are not described at all, and even the possibility thereof is not described. Of course, the separated optically active substances are three-dimensional. Can be rearranged while holding the
Nothing is known about the configuration of hydroxy-2-cyclopentenones. That is, if the 1-4-cyclopentenone alcohols obtained in the present invention are rearranged while retaining the steric structure, 4-hydroxycyclopentenones having R (+) coordination are provided, and this compound is a drug. It was first revealed by the present inventors that they are extremely useful as raw materials for prostaglandin derivatives. From the above, in the present invention, in rearrangement of optically active 4-cyclopentenone alcohols, it is necessary to rearrange while keeping the optical purity as high as possible, that is, by minimizing racemization as much as possible. For that purpose, it is necessary to carry out under appropriate conditions with respect to the base or catalyst used, temperature and the like.

The solvent used in this reaction is, for example, water, tetrahydrofuran, dioxane, acetone, benzene, toluene, ethyl acetate, chlorobenzene, heptane, dichloromethane, dichloroethane, diethyl ether, cyclohexane, or other aliphatic or aromatic solvent. Solvents inert to the reaction such as hydrocarbons, ethers, ketones, esters, halogenated hydrocarbons, alone or as a mixture, are used. Examples of the base or catalyst used in this reaction include organic tertiary amines such as triethylamine, N-methylmorpholine, N-methylpiperidine, N, N'-dimethylpiperazine, pyridine and lutidine, metals such as alumina and silica gel. Inorganic bases such as oxides, caustic soda, caustic potash, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium monohydrogenphosphate, and basic buffer solutions such as carbonate buffer solutions are suitable, and these may be used alone or in combination. Used above. The amount of such a base or catalyst used is not particularly limited, but is usually 0.05 to 60 times by mole with respect to the optically active 4-cyclopentenone alcohol as a raw material, and the organic tertiary amine or basic buffer solution is It can also be used as a solvent. The reaction temperature is in the range of -20 to 130 ° C and is appropriately selected depending on the solvent, base or catalyst used. For example,
When the reaction is carried out in the absence of water as a solvent, racemization is unlikely to occur, so that the reaction can be carried out in the range of -10 to 130 ° C. Further, in the case of an organic tertiary amine-water mixed system, the range of -10 to 90 ° C is preferable, and in the rearrangement reaction of water alone or under strong basicity, -20 to 50 ° C.
Is preferred. The reaction time is not particularly limited.

EFFECTS OF THE INVENTION From the reaction mixture thus obtained, the desired optically active 4-hydroxycyclopentenones of the general formula (I) are subjected to general operations such as extraction, liquid separation, concentration and distillation. Can be obtained with high optical purity and high yield. As the optically active 4-hydroxycyclopentenones which are the target compounds of the present application thus obtained, the following compounds having R (+) configuration are exemplified.

4-hydroxy-2-methyl-2-cyclopentenone, 2-ethyl-4-hydroxy-2-cyclopentenone, 4-hydroxy-2-n-pentyl-2-
Cyclopentenone, 2-isopropyl-4-hydroxy-2-cyclopentenone, 4-hydroxy-2-n-butyl-2-cyclopentenone, 2-isobutyl-4-hydroxy-2-cyclopentenone, 4- Hydroxy-2
-N-pentyl-2-cyclopentenone, 2-isopentyl-4-hydroxy-2-cyclopentenone, 4-hydroxy-2-n-hexyl-4-cyclopentenone,
4-hydroxy-2-n-heptyl-2-cyclopentenone, 2-allyl-4-hydroxy-2-cyclopentenone, 2- (2-cis-butenyl) -4-hydroxy-
2-cyclopentenone, 4-hydroxy-2- (ω-butynyl) -2-cyclopentenone, 2- (2-cis-pentenyl) -4-hydroxy-2-cyclopentenone,
4-hydroxy- (2-trans-pentenyl) -2-
Cyclopentenone, 2- (3-cis-hexenyl) -4
-Hydroxy-2-cyclopentenone, 4-hydroxy-2-propargyl-2-cyclopentenone, 4-hydroxy-2- (2-pentynyl) -2-cyclopentenone, 4-hydroxy-2- (2- Methylallyl) -2-
Cyclopentenone.

[0020]

EXAMPLES Next, the present invention will be described with reference to examples. Reference Example 1 dl-3-hydroxy-2-n-pentyl-4-cyclopentenone 16.8 was placed in a flask equipped with a stirrer and a thermometer.
g, p-toluenesulfonic acid 0.1 g and acetic anhydride 33.6
Charge g and continue stirring at 100 ° C. for 2 hours. After completion of the reaction, acetic anhydride is distilled off under reduced pressure, and the residue is extracted with toluene. The toluene layer is washed with 1% sodium hydrogen carbonate solution and further washed with water. Toluene was distilled off from the organic layer, and dl-3-
Acetoxy-2-n-pentyl-4-cyclopentenone
19.5 g (yield 93%) was obtained. (Bp 105-110 ° C
/0.2-0.5 mmHg) dl-3-acetoxy-2-n-pentyl-4-cyclopentenone 5 g and lipase P-
100 mg of 30A (manufactured by Amano Pharmaceutical Co., Ltd.) is stirred vigorously in 200 ml of 0.1 M phosphate buffer (pH 7.0) at 25 to 35 ° C. for 20 hours. After completion of the reaction, the reaction solution is extracted 4 times with 50 ml of methyl isobutyl ketone. The solvent was distilled off from the obtained organic layer, and the concentrated residue was purified by column chromatography with a mixed solution of ethyl acetate: toluene = 3: 5, and l-3
-Hydroxy-2-n-pentyl-4-cyclopentenone 1.8 g (yield 45%) [optical rotation α] _D ²⁰ -53.3 ° (c
= 1, chloroform)] and d-3-acetoxy-2-n
-Pentyl-4-cyclopentenone 2.54 g [optical rotation α]
_D ²⁰ + 112.0 ° (c = 1, chloroform)] was obtained.

Example 1 Next, 0.5 g of l-3-hydroxy-2-n-pentyl-4-cyclopentenone obtained in Reference Example 1, 10 g of alumina and 30 ml of benzene were stirred at 40 to 50 ° C. for 6 hours. To do. After the reaction was completed, alumina was filtered off, and methanol 1 was added.
Wash twice with 0 ml. The filtrates were combined and concentrated, and the residue was purified by column chromatography with a mixed solution of toluene-ethyl acetate = 5: 3 to obtain 0.46 g of R (+)-4-hydroxy-2-n-pentyl-2-cyclopentenone. Obtained. Optical rotation +1
2.9 ° (c = 1, chloroform)

Reference Example 2 A flask was charged with 13.8 g of dl-2-allyl-3-hydroxy-4-cyclopentenone, 0.1 g of toluenesulfonic acid and 27.6 g of acetic anhydride and heated at 90 to 100 ° C. for 3 hours. . Hereinafter, after treatment and purification according to Reference Example 1, d
16.0 g (yield 89%) of l-3-acetoxy-2-allyl-4-cyclopentenone was obtained. (Bp 80-85 ° C
/0.6-1 mmHg) dl-3-acetoxy-2-allyl-
4-cyclopentenone (5.5 g) and lipase PL (manufactured by Meito Sangyo Co., Ltd.) (0.2 g) were added to 0.1 M phosphate buffer (pH 7.0).
Stir vigorously in 250 ml at 25-35 ° C for 24 hours. After completion of the reaction, post-treatment and purification were carried out according to Reference Example 1,
-2-allyl-3-hydroxy-4-cyclopentenone
1.68 g (40% yield) [Optical rotation α] _D −28.2 ° (c =
1, chloroform)] and d-3-acetoxy-2-allyl-4-cyclopentenone 2.86 g [optical rotation α] _D ²⁰ -6
8.8 ° (c = 1, chloroform)] was obtained.

Example 2 Next, l-2-allyl-3-hydroxy-obtained in Reference Example 2
0.5 g of 4-cyclopentenone, 0.2 g of pyridine, 8 g of alumina and 30 ml of benzene are stirred for 10 hours at 30-50 ° C. After completion of the reaction, alumina is filtered off and washed with 10 ml of methanol twice. The filtrates were combined and concentrated, and the residue was purified by column chromatography with a mixed solution of toluene-ethyl acetate = 5: 3 to obtain 0.44 g of R (+)-2-allyl-4-hydroxy-2-cyclopentenone. . Optical rotation + 19.2 ° (c = 1, chloroform)

Reference Example 3 3 g of dl-3-acetoxy-2-n-pentyl-4-cyclopentenone and 150 mg of lipase-combined BSL (purified joint liquor) were added to 0.1 M phosphate buffer (pH 7.0) 1
Stir vigorously in 20 ml at 30 ° C. for 20 hours. After completion of the reaction, 1-3-hydroxy-2-n-pentyl-4-cyclopentenone 1.01 was obtained by post-treatment and purification according to Reference Example 1.
g (yield 42%) [optical rotation-51.6 ° (c = 1, chloroform)] and d-3-acetoxy-2-n-pentyl-4.
-Cyclopentenone 1.54g [Optical rotation + 107.5 ° (c =
1, chloroform) was obtained.

Example 3 Next, 0.5 g of 1-3-hydroxy-2-n-pentyl-4-cyclopentenone obtained in Reference Example 3, 4 ml of triethylamine and 0.5 g of water were mixed, and mixed with 10 to 25 Stir at 48 ° C. for 48 hours. After completion of the reaction, methyl isobutyl ketone 20
Extract 3 times with ml. The organic layers are combined and concentrated, and the residue is purified by chromatography. R (+)-4-hydroxy-2
0.44 g of -n-pentyl-2-cyclopentenone was obtained.
[Optical rotation + 11.9 ° C (c = 1, chloroform)]

Examples 4 and 5 1-2-2-allyl-3-hydroxy-4-obtained in Reference Example 2
Cyclopentenone is rearranged under the conditions shown in Table 1 to give R
The results of obtaining (+)-2-allyl-4-hydroxy-2-cyclopentenone are shown in Table 1. Post-treatment and purification after completion of the reaction were carried out according to the above-mentioned examples.

[0027]

[Table 1]

Reference Example 6 3 g of dl-3-acetoxy-2-propargyl-4-cyclopentenone and Lipase M-AP (manufactured by Amano Pharmaceutical Co., Ltd.)
50 mg to 100 ml of 0.1 M phosphate buffer (pH 6)
Stir vigorously at 25-35 ° C for 20 hours. After completion of the reaction, the reaction solution is extracted 3 times with 50 ml of hexane. The hexane layer was distilled under reduced pressure to remove the solvent, and the concentrated residue was subjected to column chromatography with a mixed solution of ethyl acetate: toluene = 1: 10 to give 1.68 g of d-3-acetoxy-2-propargyl-cyclopentenone [[α ] _D ²⁰ + 82.9 ° (c = 1, chloroform), n _D ²⁵ 1.5042] was obtained. The remaining aqueous layer extracted with hexane was 50 ml of methyl isobutyl ketone.
4 times. The methyl isobutyl ketone layers are combined and the solvent is distilled off under reduced pressure. l-3-hydroxy-2-
0.99 g of propargyl-4-cyclopentenone are obtained. Yield 42.2% [α] _D ²⁰ -42.6 ° (c = 1, chloroform), n _D ²⁵ 1.5258]

Example 6 0.9 g of l-3-hydroxy-2-propargyl-4-cyclopentenone obtained in Reference Example 6 was dissolved in 10 ml of a mixed solution of pyridine-water (volume ratio 1/10), Add 3 g of basic alumina and react at 30 ° C. for 24 hours. After completion of the reaction, alumina was filtered off, the filtrate was neutralized with a 1N aqueous hydrochloric acid solution, and extracted with 10 ml of methyl isobutyl ketone four times. The extracted oil layers were combined and concentrated, and the residue was purified by column chromatography to obtain R (+)-4-hydroxy-2-propargyl-2-cyclopentenone (0.7 g). α] _D ²⁰ + 9.4 ° (c = 1, chloroform) n] _D ²⁰ 1.5184 This compound showed absorption of carbonyl at 1715 cm ⁻¹ by IR, and the NMR data were as follows. NMR (CDCl _3, 90 MHz, internal standard TMS) 7.35 4.62 4.02 3.02 2.4-2.65 1.98 broad d broad sd multi s 1 1 1 2 2 1

Claims (1)

[Claims] 1. A general formula: (In the formula, R represents an alkyl group, an alkenyl group, or an alkynyl group. However, the substituent R at the 2-position and the hydroxyl group at the 3-position are in trans-coordination.) A general formula characterized by rearrangement of tenone alcohols while retaining a steric structure. (In the formula, R has the same meaning as described above.) A method for producing an optically active 4-hydroxycyclopentenone.