Optically active 4-hydroxy-2-cyclopentenones, and their production

Claim 2

A process for preparing an optically active 4-hydroxy-2-cyclopentenone of the formula: ##STR9## wherein R 1 is a hydrogen atom or a methyl group, R 2 is an alkyl group of not more than 12 carbon atoms, an alkenyl group of not more than 12 carbon atoms or an alkenyl group of not more than 12 carbon atoms and the asterisk (*) indicates an asymmetric configuration, which comprises subjecting a racemic or optically active 4-cyclopentenone ester of the formula: ##STR10## wherein R 1 and R 2 are each as defined above, R is a lower alkanoyloxy group and the substitutents R 1 and R 2 take a cis-configuration to asymmetric hydrolysis with an enzyme or microorganism capable of hydrolyzing the same, and treating the resultant optically active 4-cyclopentenone-alcohol of the formula: ##STR11## wherein R 1 and R 2 are each as defined above, the asterisk (*) indicates an asymmetric configuration and the substituents R 1 and R 2 take a cis-configuration with a catalyst selected from the group consisting of organic tertiary amines, metal oxides, inorganic bases and basic buffers at a temperature of -20° to 130° C., whereby the optically active 4-cyclopentenone-alcohol (II) is rearranged to the optically active 4-hydroxy-2-cyclopentenone (I) while maintaining the original steric configuration.

Claim 3

The process according to claim 1, wherein the 4-cyclopentenone ester is prepared by reacting a racemic 4-cyclopentenone-alcohol of the formula: ##STR12## wherein R 1 and R 2 are each as defined above and the substituents R 1 and R 2 take a cis-configuration with an aliphatic carboxylic acid or its reactive derivative.

Claim 4

The process according to claim 1, wherein the optically acitve 4-cyclopentenone-alcohol is prepared by subjecting a racemic 4-cyclopentenone ester of the formula: ##STR13## wherein R 1 and R 2 are each as defined above, R is a lower alkanoyloxy group and the substituents R 1 and R 2 take a cis-configuration to asymmetric hydrolysis with an enzyme or microorganism, separating the unhydrolyzed optical isomer of the 4-cyclopentenone ester and subjecting the recovered unhydrolyzed optical isomer to hydrolysis with an enzyme or microorganism.

Claim 5

The process according to claim 1, wherein R 1 is methyl.

Claim 6

The process according to claim 4, wherein the optically active 4-cyclopentenone-alcohol is the l-form and the optically active 4-hydroxy-2-cyclopentenone is the S(+)-form.

Claim 7

The process according to claim 4, wherein the optically active 4-cylopentenone-alcohol is the d-form and the optically active 4-hydroxy-2-cyclopentenone is the R(-)-form.

Claim 8

The process according to claim 4, wherein the optically active 4-cyclopentenone ester is the d-form, the optically active 4-cyclopentenone-alcohol is the l-form and the optically active 4-hydroxy-2-cyclopentenone is the S(+)-form.

Claim 9

The process according to claim 4, wherein the optically active 4-cyclopentenone ester is the l-form, the optically active 4-cyclopentenone-alcohol is the d-form and the optically active 4-hydroxy-2-cyclopentenone is the R(-)-form.

Claim 10

The process according to claim 1, wherein the catalyst is an organic tertiary amine selected from the group consisting of triethylamine, N-methylmorpholine, N-methylpiperidine, N,N'-dimethylpiperazine, pyridine and lutidine.

Claim 11

The process according to claim 1, wherein R 1 is hydrogen.

Claim 12

The process according to claim 10, wherein the optically active 4-cyclopentenone-alcohol is the l-form and the optically active 4-hydroxy-2-cyclopentenone is the R(+)-form.

Claim 13

The process according to claim 10, wherein the optically active 4-cyclopentenone ester is the d-form, the optically active 4-cyclopentenone-alcohol is the d-form and the optically active 4-hydroxy-2-cyclopentenone is the S(-)-form.

Claim 14

The process according to claim 1, wherein the catalyst is a metal oxide selected from the group consisting of alumina and silica gel.

Claim 15

The process according to claim 1, wherein the catalyst is an inorganic base selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate and potassium monohydrogen phosphate.

Claim 16

The process according to claim 1, wherein the catalyst is a basic buffer selected from the group consisting of carbonate buffers, phosphate buffers and borate buffers.

Claim 17

The process according to claim 1, wherein the catalyst is used in an amount of 0.05 to 60 parts by weight to one part by weight of the optically active 4-cyclopentenone-alcohol.

Claim 18

The process according to claim 1, wherein the enzyme is obtained from a microorganism which is a member selected from the group consisting of Rhodotorula, Trichoderma, Candida, Pseudomonas, Hansenula, Bacillus, Achromobacter, Nocardia, Chromobacterium, Flavobacterium, Rhizopus, Mucor, Aspergillus, Alcaligenes, Torulopsis, Corynebacterium, Endomyces, Saccharomyces, Arthrobacter, Metshnikowia, Pleurotus, Streptomyces, Proteus, Gliocladium, Acetobacter, Helminthosporium, Brevibacterium, Escherichia, Citrobacter, Micrococcus, Pediococcus, Klebsiella, Absidia, Geotrichem, Streptomyces, Lactobacillus, Cryptococcus, Pichia, Aureobasidium, Actimomucor, Enterobacter, Microbacterium, Penicillium and Schizophyllum.

Claim 19

The process according to claim 17, wherein the enzyme is obtained from a microorganism belonging to Pseudomonas.

Claim 20

The process according to claim 18, wherein the microorganism is Pseudomonas fragi, Pseudomonas fluorescens or Pseudomonas aeruginosa.

Claim 21

The process according to claim 17, wherein the enzyme is obtained from a microorganism belonging to Trichoderma, Candida, Hansenula, Bacillus, Achromobacter, Nocardia, Chromobacterium, Flavobacterium, Torulopsis, Metshnikowia, Pleurotus or Schizophyllum.

Claim 22

The process according to claim 20, wherein the microorganisim is Candida cylindracea, Hansenula anomala var. ciferrii, Metshnikowia pulcherrima, Pleurotus ostreatus, Schizophyllum commune, Candida krusei, Bacillus subtilis, Achromobacter parvulus, Flavobacterium lutesens, Chromobacterium iodinum, Nocardia uniformis subptsuyamanenus, Torulopsis ernobii or Trichoderma longibrachiatum.

Claim 23

The process according to claim 1, wherein the microorganism is a member selected from the group consisting of Rhodotorula, Trichoderma, Candida, Pseudomonas, Hansenula, Bacillus, Achromobacter, Nocardia, Chromobacterium, Flavobacterium, Rhizopus, Mucor, Aspergillus, Alcaligenes, Torulopsis, Corynebacterium, Endomyces, Saccharomyces, Arthrobacter, Metshnikowia, Pleurotus, Streptomyces, Proteus, Gliocladium, Acetobacter, Helminthosporium, Brevibacterium, Escherichia, Citrobacter, Micrococcus, Pediococcus, Klebsiella, Absidia, Geotrichem, Streptomyces, Lactobacillus, Cryptococcus, Pichia, Aureobasidium, Schizophyllum, Actimomucor, Enterobacter, Microbacterium and Penicillium.

Claim 24

The process according to claim 22, wherein the microorganism is the one belonging to Pseudomonas.

Claim 25

The process according to claim 22, wherein the microorganism is Pseudomonas fragi, Pseudomonas fluorescens or Pseudomonas aeruginosa.

Claim 26

The process according to claim 22, wherein the microorganism is one belonging to Trichoderma, Candida, Hansenula, Bacillus, Achromobacter, Nocardia, Chromobacter, Flavobacterium, Torulopsis, Metshnikowia, Pleurotus or Schizophyllum.

Claim 27

The process according to claim 25, wherein the microorganism is Candida cylindracea, Hansenula anomala var. ciferrii, Metshnikowia pulcherrima, Pleurotus octreatus, Schizophyllum commune, Candida krusei, Bacillus subtilis, Achromobacter parvulus, Flavobacterium lutesens, Chromobacterium iodinum, Nocardia uniformis subptsyamanenus, Torulopsis ernobii or Trichoderma longibrachiatum.

Claim 28

A process for preparing an optically active 4-hydroxy-2-cyclopentenone of the formula: ##STR14## wherein R 1 is a hydrogen atom or a methyl group, R 2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, t-butyl, iso-butyl, n-pentyl, isopentyl, n-hexyl, cyclopentyl, cyclohexyl, allyl, 2-butenyl, 3-butenyl, 2-pentynyl, n-hexyl, n-heptyl, 2-pentenyl, 3-hexynyl, propargyl or 2-methylallyl, and the asterisk (*) indicates an asymmetric configuration, which comprises subjecting a racemic or optically active 4-cyclopentenone ester of the formula: ##STR15## wherein R 1 and R 2 are each as defined above, R is a lower alkanoyloxy group and the substituents R 1 and R 2 take a cis-configuration to asymmetric hydrolysis with an enzyme or microorganism capable of hydrolyzing the same, and treating the resultant optically active 4-cyclopentenone-alcohol of the formula: ##STR16## wherein R 1 and R 2 are each as defined above, the asterisk (*) indicates an asymmetric configuration and the substitutents R 1 and R 2 take a cis-configuration with a catalyst selected from the group consisting of organic teritiary amines, metal oxides, inorganic bases and basic buffers at a temperature of -20° to 130° C., whereby the optically active 4- cyclopentenone-alcohol (II) is rearranged to the optically active 4-hydroxy-2-cyclopentenone (I) while maintaining the original steric configuration.

Claim 29

A process for preparing an optically active 4-hydroxy-2-cyclopentenone of the formula: ##STR14## wherein R 1 is a hydrogen atom or a methyl group, R 2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, t-butyl, iso-butyl, n-pentyl, isopentyl, n-hexyl, cyclopentyl, cyclohexyl, allyl, 2-butenyl, 3-butenyl, 2-pentynyl, n-hexyl, n-heptyl, 2-pentenyl, 3-hexynyl, propargyl or 2-methylallyl, and the asterisk (*) indicates an asymmetric configuration, which comprises subjecting a racemic or optically active 4-cyclopentenone ester of the formula: ##STR15## wherein R 1 and R 2 are each as defined above, R is a lower alkanoyloxy group and the substituents R 1 and R 2 take a cis-configuration to asymmetric hydrolysis with an enzyme or microorganism capable of hydrolyzing the same, and treating the resultant optically active 4-cyclopentenone-alcohol of the formula: ##STR16## wherein R 1 and R 2 are each as defined above, the asterisk (*) indicates an asymmetric configuration and the substitutents R 1 and R 2 take a cis-configuration with a catalyst selected from the group consisting of organic teritiary amines, metal oxides, inorganic bases and basic buffers at a temperature of -20° to 130° C., whereby the optically active 4- cyclopentenone-alcohol (II) is rearranged to the optically active 4-hydroxy-2-cyclopentenone (I) while maintaining the original steric configuration.