EP0101076A2
Expired / Lapsed
EP
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Process for production of optically active oxazolidinone derivative
Assignee: Kanegafuchi Chemical Industry Co Ltd
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Filing: 1983-08-11
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Granted: —
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Expires: 2003-08-11
Abstract
Abstract This invention shows a process for preparing the optically active oxazolidinone derivative [(S)-I] by utilizing microorganisms or engymes having a stereo-selective esterase activity capable of asymmetrically hydrolyzing the racemates of the acyloxyoxazolidinone derivative [(R.S)-Il], by separating the unreacted compound [(S)-II] from the hydrolyzed compound [(R)-I] and by hydrolyzing the compound [(S)-II]. The compounds are useful as intermediates for preparing optically active β-adrenergic blocking agents.
Inventors
- 👤 Shigeki Hamaguchi
- 👤 Masanori Asada
- 👤 Hiroshi Yamamura
- 👤 Junzo Hasegawa
- 👤 Hajime Kawaharada
- 👤 Kiyoshi Watanabe
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-30 16:46
CPC Classifications
C; C12; C12P; C12P17/00; C12P17/14; C07; C07D; C07D263/00; C07D263/02; C07D263/08; C07D263/16; C07D263/18; C07D263/20; C07D263/24; C12P41/00; C12P41/003; C12P41/004
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
125 words
A process for producing an optically active (S)-(+)-3-alkyl-5-acyloxymethyloxazolidin-2-one which comprises subjecting a (R,S)-(i)-3-alkyl-5-acyloxy- methyloxazolidin-2-one having the formula [(R,S)-II] wherein X is a lower alkyl group and Y is a substituted or unsubstituted alkyl group, an alkenyl group, or a substituted or unsubstituted aromatic hydrocarbon group, to the action of a microorganism or an enzyme derived from said microorganism or an animal tissue, said microorganism and enzyme having a stereoselective esterase activity capable of asymmetrically hydrolyzing the compound [(R,S)-II] so as to substantially produce an optically active (R)-(-)-3-alkyl-5-hydroxymethyloxa- zolidin-2-one having the formula [(R)-I]: wherein X is as defined above, and isolating the unreacted optically active (S)-(+)-3-alkyl-5-acyloxymethyloxazolidin-2-one having the formula [(S)-II]: wherein X and Y are as defined above, from the produced compound [(R)-I] and organic acid.
Claim 2
Dependent Claim
125 words
A process for producing an optically active (S)-(+)-3-alkyl-5-acyloxymethyloxazolidin-2-one which comprises subjecting a (R,S)-(i)-3-alkyl-5-acyloxy- methyloxazolidin-2-one having the formula [(R,S)-II] wherein X is a lower alkyl group and Y is a substituted or unsubstituted alkyl group, an alkenyl group, or a substituted or unsubstituted aromatic hydrocarbon group, to the action of a microorganism or an enzyme derived from said microorganism or an animal tissue, said microorganism and enzyme having a stereoselective esterase activity capable of asymmetrically hydrolyzing the compound [(R,S)-II] so as to substantially produce an optically active (R)-(-)-3-alkyl-5-hydroxymethyloxa- zolidin-2-one having the formula [(R)-I]: wherein X is as defined above, and isolating the unreacted optically active (S)-(+)-3-alkyl-5-acyloxymethyloxazolidin-2-one having the formula [(S)-II]: wherein X and Y are as defined above, from the produced compound [(R)-I] and organic acid.
Claim 3
Dependent Claim
13 words
The process of Claim 1, wherein X is t-butyl group or isopropyl group.
Claim 4
Dependent Claim
23 words
The process of Claim 1, wherein Y is an aryl group, a substituted aryl group, an aralkyl group or a substituted aralkyl group.
Claim 5
Dependent Claim
38 words
The process of Claim 1, wherein said microorganism belongs to a genus selected from the group consisting of the genus Enterobacter, Klebsiella, Micrococcus, Citrobacter, Escherichia, Pseudomonas, Staphylococcus, Alcaligenes, Achromobacter, Streptomyces, Candida, Debaryomyces, Endomyces, Hansenula,-Geotrichum, Kluyveromyces, Metschnikowia and Pichia.
Claim 6
Dependent Claim
68 words
The process of Claim 1, wherein said microorganism belongs to a species selected from the group consisting of Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Micrococcus luteus, C itrobacter freundii, Escherichia coli, Pseudomonas cruciviae, Pseudomonas fluorescens, Staphylococcus aureus, Alcaligenes faecalis, Achromobacter parvulus,' Streptomyces flavovirens, Streptomyces aureus, Candida pseudotropicalis, Candida kefyr, Debaryomyces hansenii, Endomyces geotrichum, Hansenula anomala, Hansenula minuta, Geotrichum candidum, Kluyveromyces fragilis, Metschnikowia pulcherrima, Pichia farinosa and Pichia membranaefaciens.
Claim 7
Dependent Claim
27 words
The process of Claim 1, wherein the microorganism is cultured and reacted in a medium containing the compound [(R,S)-III at a pH of from 4 to 8.
Claim 8
Dependent Claim
39 words
The process of Claim 1, wherein the compound (I) is subjected to the action of a cultured broth obtained by culturing the microorganism in a culture medium or a cell suspension prepared by separating cells from said cultured broth.
Claim 9
Dependent Claim
43 words
The process of Claim 7, wherein the microorganism is cultured at a pH of from 3 to 11, and the compound [(R,S)-II] is subjected to the action of the cultured broth or the cell suspension at a pH of from 4 to 8.
Claim 10
Dependent Claim
36 words
The process of Claim 1, wherein said enzyme is prepared from a cell-free extract obtained by homogenizing the cells of said microorganism, or a partially purified enzyme obtained by fractionating said cell-free extract with ammonium sulfate.
Claim 11
Dependent Claim
14 words
The process of Claim 1, wherein said animal is a mammal or a bird.
Claim 12
Dependent Claim
15 words
The process of Claim 1, wherein said animal tissue is a liver or a pancreas.
Claim 13
Dependent Claim
39 words
The process of Claim 1, wherein said enzyme is a crude enzyme obtained by fractionating a homogenate of the animal tissue with a member selected from the group consisting of ethanol, acetone, ammonium sulfate and an ion exchange resin.
Claim 14
Dependent Claim
36 words
The process of Claim 1, wherein the compound [( R ,S)-I] is subjected to the action of said enzyme at a temperature of from 10° to 50°C and a p H of from 4 to 8.
Claim 15
Dependent Claim
28 words
The process of Claim 1, wherein the compound [(S)-II] is isolated from the produced compound [(R)-I] and organic acid by extracting the reaction mixture with an organic solvent.
Claim 16
Dependent Claim
27 words
The process of Claim 1, wherein the compound [(S)-II] is separated from the produced compound [(R)-I] and organic acid by subjecting the reaction mixture to column chromatography.
Claim 17
Dependent Claim
27 words
The process of Claim 1, wherein the compound [(S)-II] is isolated from the produced compound [(R)-I] and organic acid by treating the reaction mixture with fractional distillation.
Claim 18
Dependent Claim
145 words
A process for preparing an optically active (S)-(+)-3-alkyl-5-hydroxymethyloxazolidin-2-one which comprises subjecting a (R,S)-(±)-3-alkyl-5-acyloxy- methyloxazolidin-2-one having the formula [(R,S)-II]: wherein X is a lower alkyl group and Y is a substituted or unsubstituted alkyl group, an alkenyl group, or a substituted or unsubstituted aromatic hydrocarbon group, to the action of a microorganism or an enzyme derived from said microorganism or an animal tissue, said microorganism and enzyme having a stereoselective esterase activity capable of asymmetrically hydrolyzing the compound [(R,S)-II] so as to substantially produce an optically active (R)-(-)-3-alkyl-5-hydroxymethyloxa- zolidin-2-one having the formula [(R)-I]: wherein X is as defined above, isolating the unreacted optically active (S)-(+)-3-alkyl-5-acyloxymethyloxazolidin-2-one having the formula [(S)-II]: wherein X and Y are as defined above, from the produced compound [(R)-I] and organic acid, and hydrolyzing the compound [(S)-II] to give the optically active (S)-(+)-3-alkyl-5-hydroxymethyloxazolidin-2-one having the formula I(S1-I]: wherein X is as defined above.
Claim 19
Dependent Claim
145 words
A process for preparing an optically active (S)-(+)-3-alkyl-5-hydroxymethyloxazolidin-2-one which comprises subjecting a (R,S)-(±)-3-alkyl-5-acyloxy- methyloxazolidin-2-one having the formula [(R,S)-II]: wherein X is a lower alkyl group and Y is a substituted or unsubstituted alkyl group, an alkenyl group, or a substituted or unsubstituted aromatic hydrocarbon group, to the action of a microorganism or an enzyme derived from said microorganism or an animal tissue, said microorganism and enzyme having a stereoselective esterase activity capable of asymmetrically hydrolyzing the compound [(R,S)-II] so as to substantially produce an optically active (R)-(-)-3-alkyl-5-hydroxymethyloxa- zolidin-2-one having the formula [(R)-I]: wherein X is as defined above, isolating the unreacted optically active (S)-(+)-3-alkyl-5-acyloxymethyloxazolidin-2-one having the formula [(S)-II]: wherein X and Y are as defined above, from the produced compound [(R)-I] and organic acid, and hydrolyzing the compound [(S)-II] to give the optically active (S)-(+)-3-alkyl-5-hydroxymethyloxazolidin-2-one having the formula I(S1-I]: wherein X is as defined above.
Claim 20
Dependent Claim
13 words
The process of Claim 17, wherein X is t-butyl group or isopropyl group.
Claim 21
Dependent Claim
23 words
The process of Claim 17, wherein Y is an aryl group, a substituted aryl group, an aralkyl group or a substituted aralkyl group.
Claim 22
Dependent Claim
39 words
The process of Claim 17, wherein said microorganism belongs to a genus selected from the group consisting of the genus Enterobacter, Klebsiella, Micrococcus; Citrobacter, Escherichia, Pseudomonas, Staphylococcus, Alcaligenes, Achromobacter, Sterptomyces, Candida, Debaryomyces, Endomyces, Hansenula, Geotrichum, Kluyveromyces, Metschnikowia and Pichia.
Claim 23
Dependent Claim
68 words
The process of Claim 17, wherein said microorganism belongs to a species selected from the group consisting of Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Micrococcus luteus, Citrobacter freundii, Escherichia coli, Pseudomonas cruciviae, Pseudomonas fluorescens, Staphylococcus aureus, Alcaligenes faecalis, Achromobacter parvulus, Streptomyces flavovirens, Streptomyces aureus, Candida pseudotropicalis, Candida kefyr, D ebaryomyces hansenii, Endomyces geotrichum, Hansenula anomala, Hansenula minuta, Geotrichum candidum, Kluyveromyces fragilis, Metschnikowia pulcherrima, Pichia farinosa and Pichia membranaefaciens.
Claim 24
Dependent Claim
27 words
The process of Claim 17, wherein the microorganism is cultured and reacted in a medium containing the compound [(R,S)-II] at a pH of from 4 to 8.
Claim 25
Dependent Claim
39 words
The process of Claim 17, wherein the compound [(R,S)-II] is subjected to the action of a cultured broth obtained by culturing the microorganism in the culture medium or a cell suspension prepared by separating cells from said cultured broth.
Claim 26
Dependent Claim
43 words
The process of Claim 23, wherein said microorganism is cultured at a pH of from 3 to 11, and the compound [(R,S)-II] is subjected to the action of the cultured broth or the cell suspension at a pH of from 4 to 8.
Claim 27
Dependent Claim
36 words
The process of Claim 17, wherein said enzyme is prepared from a cell-free extract obtained by homogenizing the cells of said microorganism or a partially purified enzyme obtained by fractionating said cell-free extract with ammonium sulfate.
Claim 28
Dependent Claim
14 words
The process of Claim 17, wherein said animal is a mammal or a bird.
Claim 29
Dependent Claim
15 words
The process of Claim 17, wherein said animal tissue is a liver or a pancreas.
Claim 30
Dependent Claim
39 words
The process of Claim 17, wherein said enzyme is a crude enzyme obtained by fractionating a homogenate of the animal tissue with a member selectied from the group consisting of ethanol, acetone, ammonium sulfate and an ion exchange resin.
Claim 31
Dependent Claim
34 words
The process of Claim 17, wherein the compound [(R,S)-II] is subjected to the action of said enzyme at a temperature of from 10°C to 50°C and a pH of from 4 to 8. -
Claim 32
Dependent Claim
30 words
The process of Claim 17, wherein the compound [(S)-II] is isolated from the produced compound [( R )-I] and organic acid by extracting the reaction mixture with an organic solvent.
Claim 33
Dependent Claim
27 words
The process of Claim 17, wherein the compound [(S)-II] is separated from the produced compound [(R)-I] and organic acid by subjecting the reaction mixture to column chromatography.
Claim 34
Dependent Claim
27 words
The process of Claim 17, werein the compound [(S)-II] is isolated from the produced compound [(R)-I] and organic acid by treating the reaction mixture with fractional distillation.
Claim 35
Dependent Claim
25 words
The process of Claim 17, wherein the compound [(S)-I] is prepared by chemically hydrolyzing the compound [(S)-II] at a pH of from 8 to 14.
Claim 36
Dependent Claim
28 words
The process of Claim 17, wherein the compound [(S)-I] is prepared by enzymatically hydrolyzing the compound [(S)-II] with an hydrolase at a pH of from 4 to 8.
References Cited (Backward Citations)
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