JPH0615487B2 - Process for producing optically active 4-hydroxycyclopentenones - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention has the general formula (I) (In the formula, R represents an alkyl group, an alkenyl group or an alkynyl group.) The present invention relates to a novel process for producing an optically active 4-hydroxycyclopentenone.

The optically active 4-hydroxycyclopentenones represented by the above general formula (I) are useful as intermediates for agricultural chemicals or fragrances, and can be used, for example, as important intermediates for prostaglandin derivatives.

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.

Such optically active 4-hydroxycyclopentenones represented by the general formula (I) are d-4-hydroxy-2
-Acetate of cyclopentenone can also be synthesized by asymmetric hydrolysis using an enzyme or the like,
It is not always satisfactory in terms of optical purity.

From the above, the present inventors have proposed a method for obtaining an optically active 4-hydroxycyclopentenone represented by the general formula (I) at a low cost and industrially advantageously with high purity and high yield. As a result of the research, the present invention has been achieved.

That is, the present invention is represented by the general formula (IV) (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 represented by the general formula
It is a process for producing an optically active 4-hydroxycyclopentenone represented by (I).

Here, the optically active 4-cyclopentenone alcohols represented by the general formula (IV) are represented by the general formula (III) (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.) The indicated d-4-cyclopentenone esters are
Obtained by asymmetric hydrolysis using an enzyme or a microorganism.

Further, the d-4-cyclopentenone esters represented by the general formula (III) are represented by the general formula (II) (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.) D-4-cyclopentenone alcohols and fats It can be obtained by reacting (esterifying) a group carboxylic acid.

The present invention is also a method for producing the optically active 4-cyclopentenone alcohols represented by the general formula (I) by combining the above respective reactions as shown below.

Hereinafter, the present invention will be described in detail.

The 4-cyclopentenone ester represented by the general formula (III) can be easily and highly yielded by reacting the d-4-cyclopentenone alcohol represented by the general formula (III) with an aliphatic carboxylic acid. Can be manufactured at a rate.

Here, the d-4-cyclopentenone alcohols used as a raw material can be easily produced, for example, by rearranging furancarbinol as shown in the following formula, and d-4-cyclopentenone alcohol The following compounds are illustrated as a class.

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.

Further, examples of 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,
Chloracetyl chloride or bromide, dichloroacetyl chloride or bromide.

The reaction between the d-4-cyclopentenone alcohol and the 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.

When a solvent is used in this reaction, the solvent may be, for example, tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, hexane or the like. Solvents such as aromatic hydrocarbons, ethers, halogenated hydrocarbons and the like which are inert to the reaction may be used alone or as a mixture. The amount used can be used without particular limitation.

The aliphatic carboxylic acids used in the reaction are the raw materials d-4.
-It is necessary to have 1 equivalent or more with respect to cyclopentenone alcohols, and the upper limit is not particularly limited, but it is preferably 1 to 4 equivalents.

Examples of the catalyst 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 to 5 equivalents relative to d-4-cyclopentenone alcohol.

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.

The reaction temperature is usually -20 ° C to 150 ° C, preferably -10 ° C to 120 ° C.

The reaction time is not particularly limited.

By such a reaction, d represented by the general formula (III)
The -4-cyclopentenone esters are obtained easily and in good yields, which are the usual separation means, for example extraction,
Although it can be easily isolated from the reaction mixture by liquid separation, concentration, distillation, etc., 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 having the ability to hydrolyze the 4-cyclopentenone esters represented by the general formula (III). Then, one of the optically active forms of the esters is hydrolyzed.

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

Specific examples of such microorganisms include microorganisms belonging to the following genera.

Enterobacter, Elsobacter, Brevibacterium, Pseudomonas, Alcaligenes, Micrococcus, Chromobacterium, Cyclobacterium, Corynebacterium, Bacillus, Lactobacillus, Trichoderma, Candida Genus, Saccharomyces, Rhodotorula, Cryptococcus, Torrlopsis, Pichia, Penicillium, Aspergillus, Rhizopus, Mucor, Aureobasidium, Actinomucor, Nocardia, Streptomyces, Hansenula, Microorganisms belonging to the genus Achromobacter Examples of microorganisms belonging to each of these genera include the following.

Rhodotorula minuta IFO-03
87, IFO-0412, Rhodotorula
ubra IFO-0870, Rhodotorula
minuta var texensis IFO-
0879, Trichoderma longibra
chiatum IFO-4847, Candida
crusei out-6007, Candida c
ylin-dracea, Candida tropi
calis PK233, Candida utilu
s IFO-1086, Pseudomonas fr
agi IFO-3458, Pseudomonas
putida IFO-12996, Pseudomo
NAS Fluorescens IFO-3903,
Pseudomonas aeruginosa IF
O-3080, Bacillus cereus IF
O-3466, Bacillus subtilis
ATCC-6638 Bacillus plumil
us IFO-12092, Bacillus sub
tilis var niger IFO-3108,
Nocardia uniformis subsuyanarenus ATCC-2180
6, Nocardia uniformis IFO-1
3072, Chromobacterium choc
olatum IFO-3758, Chromobac
terium iodinum IFO-3558, F
lavobacterium arbonescens
IFO-3750, Flavobacterium
heparinum IFO-12017 Rizop
us chinensis IFO-4768, Muc
or javanicus IFO-4572, Aspergillus niger ATCC-96
42, Alcaligenes faecalis I
FO-12669 Torulopsis candida IFO-07
68, Corynebacterium sepedonic
um IFO-13763, Saccharomyces rouxii IFO-0
505, Arthrobacter simplex IFO-
3530, Streptomyces greases IFO-
3356, Brevibacterium ammoniagen
es IFO-12072, Brevibacterium divaricatu
m ATCC-14020, Micrococcus varians IFO-3
765, Micrococcus luteus IFO-30
66, Enterobacter cloacae IFO-
3320, Conynebacterium ezui ATCC
7699, Lacto bacillus casei IFO
3322, Cryptococcus albidus IFO-
0378, Piria polymorpha IFO 1166 penicillium frequentans I
FO 5692, Aureobasidium pullulans I
FO 4464, Actimucor elegans IFO 40
22 Hansenula anomala var cif
erri out 6095, Hansenula anomala IFO-011
8, Achromobacter parvulus IF
O-13181, Achromobacter simplex IFO
-12069, For the culture of the above-mentioned microorganism, a liquid culture is usually obtained by carrying out liquid culture according to a conventional method. For example, sterilized liquid medium [for molds and yeasts, malt extract / yeast extract medium (5 g of peptone, 10 g of glucose, 3 g of malt extract, 3 g of yeast extract are dissolved in 1 water to obtain pH 6.5), bacteria For use, sweetened broth medium (1 part water to 10 parts glucose)
g, peptone 5g, meat extract 5g, Nacl 3g,
pH 7.2)]] and inoculated with a microorganism, usually at 20-40 ° C.
Reciprocal shaking culture for 1 to 3 days. Moreover, you may perform solid culture as needed.

Some of these esterases originating from microorganisms are commercially available and can be easily obtained. Specific examples of commercially available esterases include the followings.

Pseudomonas lipase (manufactured by Amano Pharmaceuticals) Lipase of genus Aspergillus (lipase AP (manufactured by Amano Pharmaceuticals)), Lipase M-Ap of genus Mucor (manufactured by Amano Pharmaceuticals), lipase of Candida syrindasse (lipase MY (manufactured by Meito Sangyo) )) Alcaligenes lipase (lipase PL
(Manufactured by Meito Sangyo), lipase of Achromobacter (lipase AL (manufactured by Meito Sangyo)), lipase of Arthrobacter (lipase-combined BSL (combined liquor purification)), lipase of Chromobacterium (Toyo) Brewed), Rhizopus
Derema lipase (Talipase (Tanabe Seiyaku)), Rhizopus lipase (Lipase Saiken (Osaka Bacterial Research Institute)) In addition, animal / plant esterases can also be used. I can list things.

Steapsin, pancreatin, pig liver esterase, Wheat Germ esterase Esterase (hydrolase) used in this reaction,
As the use form of the enzyme obtained from animals, plants and microorganisms, there are various forms such as purified enzyme, crude enzyme, enzyme-containing product, microbial culture solution, culture product, fungus body, culture solution and processed product thereof. It can be used as necessary, and the enzyme and the microorganism can 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 usually carried out by vigorously stirring the d-4-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 or potassium phosphate, a buffer solution of an organic acid salt such as sodium acetate or sodium citrate, etc. is used, and its pH is an alkalophilic bacterium. PH of 8 to 11 is preferable for the culture broth and alkaline esterase, and pH 5 to 8 is preferable for the culture broth of non-alkalophilic microorganisms and the esterase not having alkali tolerance.

The concentration is usually 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) can be obtained by the general formula
It is produced by rearrangement of optically active 4-cyclopentenone alcohols represented by (IV) in the presence of a base or a catalyst while maintaining the steric structure.

Incidentally, the optically active 4-cyclopentenone alcohols represented by the general formula (IV), which are the raw materials of this reaction step, have not been known so far, and Tetrahed only as a d-form.
Oron Letter, No. 39, 3555 to 3558 (1976) describes that the pair is (i).

However, the specific description of the pair of (i) optically active substances, the separation was not described at all, and even the possibility thereof was not described. Of course, the separated optically active substance retained the steric structure. 4-Hydroxy-2 obtained by rearrangement while maintaining the stereochemistry
Nothing is known about the configuration of cyclopentenones.

That is, the -4-cyclopentenone alcohols obtained in the present invention are rearranged while retaining the steric structure to give 4-hydroxycyclopentenones having R (+) coordination. It was first revealed by the present inventors that they are extremely useful as a raw material for a glandin derivative. 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 for the base or catalyst used, temperature and the like.

Examples of the solvent used in this reaction include water, tetrahydrofuran, dioxane, acetone, benzene,
Solvents such as aliphatic or aromatic hydrocarbons such as toluene, ethyl acetate, chlorobenzene, heptane, dichloromethane, dichloroethane, diethyl ether, and cyclohexane, ethers, ketones, esters, halogenated hydrocarbons, which are inert to the reaction, alone or as a mixture. Is 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 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 in water alone or under strong basicity,
The range of 20 to 50 ° C is preferable.

From the reaction mixture thus obtained, extraction, liquid separation,
General formula to be obtained by general operations such as concentration and distillation
The optically active 4-hydroxycyclopentenones of (I) can be obtained with good 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.

Example 1 A flask equipped with a stirrer and a thermometer was charged with d-3-hydroxy-2-n-pentyl-4-cyclopentenone 16.8.
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 to obtain 19.5 g (yield 93%) of d-3-acetoxy-2-n-pentyl-4-cyclopentenone. (Bp 105 to 110 ° C./0.2 to 0.5 mmHg) 5 g of d-3-acetoxy-2-n-pentyl-4-cyclopentenone and 100 mg of lipase P-30A (manufactured by Amano Pharmaceutical Co., Ltd.) in 0.1 M phosphate buffer (pH 7.0). ) 200
vigorous stirring at 25-35 ° C. for 20 hours.
After the reaction is completed, the reaction solution is treated with methyl isobutyl ketone 50m.
4 times. The solvent was distilled off from the obtained organic layer,
The concentrated residue was purified by column chromatography with a mixed solution of ethyl acetate: toluene = 3: 5 to give -3-hydroxy-2-n.
-Pentyl-4-cyclopentenone 1.8 g (yield 45
%) [Light intensity ▲ α] ²⁰ _D ▼ -53.3 ° (c = 1, chloroform)] and d-3-acetoxy-2-n-pentyl-4.
-Cyclopentenone 2.54g [Light intensity ▲ α] ²⁰ _D ▼ ＋ 112.0
(C = 1, chloroform)] was obtained.

Next, 0.5 g of -3-hydroxy-2-n-pentyl-4-cyclopentenone obtained here, 10 g of alumina and 30 m of benzene are stirred at 40 to 50 ° C for 6 hours. After the reaction was completed, the alumina was separated and further methanol 1
Wash twice at 0 m. The liquids 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.

Illumination degree + 12.9 ° (c = 1, chloroform) Example 2 A flask was charged with 13.8 g of d-2-allyl-3-hydroxy-4-cyclopentenone, 0.1 g of toluenesulfonic acid and 27.6 g of acetic anhydride, and 90 Heat at ~ 100 ° C for 3 hours. Hereinafter, after treatment and purification according to Example 1, d
16.0 g (yield 89%) of -3-acetoxy-2-allyl-4-cyclopentenone was obtained.

(Bp 80 to 85 ° C./0.6 to 1 mmHg) d-3-acetoxy-2-allyl-4-cyclopentenone 5.5 g and lipase PL (manufactured by Meito Sangyo Co., Ltd.) 0.2 g
25 to 35 in M phosphate buffer (PH7.0) 250 m
Stir vigorously at 24 ° C. for 24 hours. After completion of the reaction, post-treatment and purification were carried out according to Example 1, and 2-allyl-3-hydroxy-4-cyclopentenone 1.68 g (yield 40%). [Light rotation α] _D- 28.2 ° (c = 1, chloroform)] and d-3-acetoxy-2-allyl-4-cyclopentenone (2.86 g) [diameter [alpha] ²⁰ _D ▼ + 68.8 ° (c = 1, chloroform)] were obtained.

Then the 2-allyl-3-hydroxy-4-obtained here
Cyclopentenone 0.5g, Pyridine 0.2g, Alumina 8g
And 30 m of benzene are stirred at 30 to 50 ° C. for 10 hours.

After the reaction was completed, the alumina was separated and methanol 10 m
Wash twice with. The liquids were combined and concentrated, and the residue was purified by column chromatography with a mixed liquid of toluene-ethyl acetate = 5: 3, and R (+)-2-allyl-4-hydroxy-2-
0.44 g of cyclopentenone was obtained.

Illumination degree + 19.2 ° (c = 1, chloroform) Example 3 3 g of d-3-acetoxy-2-n-pentyl-4-diclopentenone and 150 mg of lipase combined BSL (purified joint liquor) were added to 0.1M phosphate buffer (PH7). .0) 120
vigorous stirring at 30 ° C. for 20 hours. After the completion of the reaction, post-treatment and purification were carried out according to Example 1, and 1.03 g of -3-hydroxy-2-n-pentyl-4-cyclopentenone
(Yield 42%) [Light rotation: -51.6 ° (c = 1, chloroform)] and d-3-acetoxy-2-n-pentyl-4-
Diclopentenone 1.54g [Light intensity + 107.5 ° (c = 1,
Chloroform)] was obtained.

Next, 0.5 g of -3-hydroxy-2-n-pentyl-4-cyclopentenone obtained here and 4 m of triethylamine
And 0.5 g of water are mixed and stirred at 10 to 25 ° C. for 48 hours. After completion of the reaction, 20m of methyl isobutyl ketone
Extract 3 times. The organic layers are combined and concentrated, and the residue is purified by chromatography.

0.44 g of R (+)-4-hydroxy-2-n-pentyl-2-cyclopentenone was obtained. [Light intensity + 11.9 ° (c =
1, chloroform)] Examples 4 and 5-2-allyl-3-hydroxy-4-obtained in Example 1
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.

Example 6 d-3-acetoxy-2-propargyl-4-cyclopentenone 3 g and lipase M-AP (manufactured by Amano Pharmaceutical Co., Ltd.)
50 mg to 100 m 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 m of hexane. The solvent was distilled off from the hexane layer under reduced pressure, 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-4-cyclopentenone. ▲ α] ²⁰ _D ▼ + 82.9 ° (c = 1,
Chloroform) to give the ▼ n ²⁵ _D ▼ 1.5042}.

Further, the remaining aqueous layer extracted with hexane is extracted 4 times with 50 m of methyl isobutyl ketone. The methyl isobutyl ketone layers are combined and the solvent is distilled off under reduced pressure.

0.99 g of -3-hydroxy-2-propargyl-4-cyclopentenone are obtained.

Yield 42.2% {▲ α] ²⁰ _D ▼ -42.6 ° (c = 1, chloroform), ▲ n ²⁵ _D ▼ 1.5258] -3-hydroxy-2-propargyl-4 obtained here
-0.9 g of cyclopentenone was added to pyridine-water (volume ratio 1/1
0) dissolved in a mixed solution of 10 m to form basic alumina 3
g and the mixture is reacted at 30 ° C. for 24 hours.

After the reaction was completed, the alumina was separated, the solution was neutralized with a 1N aqueous hydrochloric acid solution, and the solution was adjusted to 4 with 10 m of methyl isobutyl ketone.
Extract once. The extracted oil layers were combined and concentrated, and the residue was purified by column chromatography to give R (+)-4-
Hydroxy-2-propargyl-2-cyclopentenone
0.7 g was obtained.

▲ α] ²⁰ _D ▼ + 9.4 ° (c = 1, chloroform) ▲ n] ²⁰ _D ▼ 1.5184 Carbonyl absorption was observed at 1715 cm ⁻¹ by IR, and the NMR data were as follows. .

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Claims (2)

[Claims] 1. A general formula (In the formula, R represents an alkyl group, an alkenyl group, or an alkynyl group, and R ₁ represents an acyloxyl group. However, the substituent R at the 2-position and the substituent R _{1 at the} 3-position are in trans-coordination. ) D-4-cyclopentenone ester represented by
Asymmetrically hydrolyzed using enzymes or microorganisms to give a general formula (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.) A general formula characterized by obtaining and then rearranging while retaining the three-dimensional shape (In the formula, R has the same meaning as described above.) A method for producing an optically active 4-hydroxycyclopentenones. 2. 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.) D-4-cyclopentenone General formula for reacting alcohols with aliphatic carboxylic acids (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.) The indicated d-4-cyclopentenone esters are obtained and then asymmetrically hydrolyzed using an enzyme or a microorganism to give a compound of the general formula (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.) A general formula characterized by the fact that it is obtained and then rearranged while retaining the three-dimensional shape (In the formula, R has the same meaning as described above.) A method for producing an optically active 4-hydroxycyclopentenones.