CA2116004A1 - Arylalkanoic acid resolution - Google Patents
Arylalkanoic acid resolutionInfo
- Publication number
- CA2116004A1 CA2116004A1 CA 2116004 CA2116004A CA2116004A1 CA 2116004 A1 CA2116004 A1 CA 2116004A1 CA 2116004 CA2116004 CA 2116004 CA 2116004 A CA2116004 A CA 2116004A CA 2116004 A1 CA2116004 A1 CA 2116004A1
- Authority
- CA
- Canada
- Prior art keywords
- ketoprofen
- enzyme
- ester
- crude
- ccl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000002253 acid Substances 0.000 title abstract description 8
- 229960000991 ketoprofen Drugs 0.000 claims abstract description 12
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 230000036983 biotransformation Effects 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 102000004882 Lipase Human genes 0.000 claims description 4
- 108090001060 Lipase Proteins 0.000 claims description 4
- 239000004367 Lipase Substances 0.000 claims description 4
- 235000019421 lipase Nutrition 0.000 claims description 4
- 241000179532 [Candida] cylindracea Species 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 abstract description 22
- 108090000790 Enzymes Proteins 0.000 abstract description 22
- 239000000203 mixture Substances 0.000 abstract description 2
- NPECQMCAJUDCRG-UHFFFAOYSA-N 2-(3-benzoylphenyl)-2-methyldecanoic acid Chemical compound C(CCCCCCC)C(C(O)=O)(C)C1=CC(C(=O)C2=CC=CC=C2)=CC=C1 NPECQMCAJUDCRG-UHFFFAOYSA-N 0.000 abstract 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 239000011942 biocatalyst Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- HGRGFZWEVKNHJT-UHFFFAOYSA-N 2-(3-benzoylphenyl)-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 HGRGFZWEVKNHJT-UHFFFAOYSA-N 0.000 description 1
- GAWAYYRQGQZKCR-UHFFFAOYSA-N 2-chloropropionic acid Chemical compound CC(Cl)C(O)=O GAWAYYRQGQZKCR-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010960 commercial process Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
In a process for preparing predominantly one enantiomer of an optically-active 2-arylalkanoic acid by biotransformation, using an appropriate enzyme, of a mixture of enantiomers of an ester of the acid, the ester is derived from an alcohol of more than 4 carbon atoms, and the enzyme is in crude or only partially purified form. For example, S-ketoprofen can be thus prepared economically and in high ee, from racemic octyl ketoprofen.
Description
WO93/04190 2116 0 0 ~ PCT/EP92/01896 ARYLALKANOIC ACID RESOLUTION
Field of the Invention This invention relates to a process for resolving arylalkanoic acids, by a biotransformation according to the following reaction scheme:
Ar enzyme ~r ~0 CO~H Ar\ ~C~R' R ~ R ~ H R
wherein R' is an alkyl group, Ar is an aromatic residue and, for example, R is an aliphatic residue of 1 to 4 carbon atoms.
Backaround of the InventiQn In the prior art, a preference has of~en been made for carrying out such biotransformations with a small alkyl residue ~for R'. Thus, in EP-A-019662S, where 2-halopropionic acids are resolved by Candida cylindracea lipase (CCL) in a two-phase system, R' is de~ined as C1-C~
alkyl. Moreover, later work with this enzyme, as described by Wu et al, J. Am. Chem. Soc. (1990~ 112, 1990-5, concentrates on using the methyl ester for resolution of arylpropionic acids. The enzyme is purified, by additidn of sodium deoxycholate to the enzyme solution . and subsequent precipitation of the protein in 1:1 ethanol/diethyl ether.
This preference, for esters of ketoprofen at least, when using a crude preparation of CCL, is supported by the Table, below: enantiospecificity, as determined by the enantiomeric excess (ee) of the acid formed, declines with chain length from R'=methyl to R'=n-propyl.
Cambou and Klibanov, Appl. Biochem. Biotechnol. (1984) ~:255-60, report that CCL hydrolysis is selective for octyl 35 2-chloropropionate but not for the methyl e~ter. However, the failure of this methyl ester to exhibit SU~3STITUTE SHE~T
211600~
enantiospecificity is considered to be due to its water-solubility, causing it not to form an interface.
SummarY of the Invention As also shown in the Table, it has now surprisingly been found that when the esters are derived from increasingly longer chain alcohols, the ee subsequently increases to a higher figure thian that obtainable with the methyl ester, of approximately 98% at R'-C~ and C10 n-alkyl.
According to the present invention, the reaction illustrated above is conducted using crude (or partially-purified) enzyme, and R' has more than 4, e.g. 5, 6 or 7 to 15 to 20 C atoms. Subsequent work with purified enzyme showed that high ee was achieved whatever the chain length, but the purification adds to the overall cost.
DescriDtion of the Invention CCL has been identified as the most promising en2yme for enantiosspecific hydrolysis of racemic esters of ketoprofen. This enzyme gives the fastest rate and, unlike the majority of other active lipases, preferentially hydrolyses the S-ester, enabling simple purification of S-ketoprofen.
It appears that contaminating activities in crude CCL
do not carry out the non-selective hydrolysis with esters of long-chain alcohols. Thus, there is advantage in using a long chain ester to enable the economy of using a crude or only partially pure enzyme. More particularly, the fact that, say, octyl Xetoprofen can be used as a substrate with partially purified enzyme producing S-ketoprofen with ee of greater than 95% allows the development of a commercial process.
The following Examples illustrate the invention or are comparative.
Exam~les CCL is used as the biocatalyst to resolve racemic mixtures of various alkyl esters of ketoprofen; S-ketoprofen is formed. The same reaction conditions are used, i.e. lO ml of O.l M potassium phosphate, pH 7.5 plus SUBSTITUTE ~;HEET
W093tO4190 211 6 0 D ~ PCT/EP92/01896 2 ml cyclohexane, lOO mg alkyl ketoprofen, 50 mg enzyme, 30C. Results are given in the Table.
The CCL is used in crude form, or after a three-step purification, comprising water extraction, filtra-tion and column separation, as follows: The enzyme wasresuspended at 50 mg/ml in deionised water. After stirring at room temperature for 30 minutes, the inso-luble material was spun out. The supernatant was dia-filtered against lO volumes of McIlvaine's buffer (20 mM K2HP04 + 10 mM citric acid, pH 3.7) at room tempera-ture. Following diafiltration, the enzyme solution was concentrated to l/5 of its original volume. The enzyme solution was bonded onto an AP-sephadex C 50 column (20 ml enzyme solution: 20 ml of gel) equilibrated with McIlvaine's buffer. The column was washed with McIlvaine's buffer + 20 mM NaCl. After the first peak had eluted and the absorbance (at 280 nm) had returned to baseline, McIlvaine's buffer + 200 mM NaCl was used to elute a second protein peak.
The final step of purification yielded two activi-ties. The protein eluted at a higher salt concentration was foun~ to be highly enantiospecific.
The respective properties of the CCL biocatalysts were:
Crude Purified _ _ _ _ _EAzyme Enzyme Mass 50 g 2.l g Powder Activity 150 U/mg 680 U/mg Yield (lOO~) 19%
E (enantiospecifity ratio of enzyme)B 15 >200 A - Assayed using olive oil as substrate, 37C, pH 7.5.
B - lOO ml O.l M ketoprofen: pH 6.5, 2 ml cyclohexane, lOO mg methyl ketoprofen, 30,000 U CCL, 30C.
Table: Enantiomeric excess values~~) of S-ketoprofen __ by Candida cvlindracea lipase hydrolysis of esters from various alcohols.
SUBSTITUTE SHEET
~ _ . .
n-alcohols Usinq crudeUsing enzyme no . carbon enzyme purif ied on a SP
atoms Sephadex gel column ee c E ee c E
1 75_0.57 39 99 0.48 >200_ 2 540.43 5 3 _ 340.45 _ 3 4 700.44 10 I . , , , I
_ 5 890. 33 26 _ _ I -_ I
1 6 920. 27 33 _ I 7 97_ 0. 28 95 . _ -- _ 8 98o. 32 136 >99 0 . 23 >200 I _. ., __ . .
980. 18 127 ~ _ .
1 18 95 0. 16 43 - _ SUBSTITUTE SHEET
Field of the Invention This invention relates to a process for resolving arylalkanoic acids, by a biotransformation according to the following reaction scheme:
Ar enzyme ~r ~0 CO~H Ar\ ~C~R' R ~ R ~ H R
wherein R' is an alkyl group, Ar is an aromatic residue and, for example, R is an aliphatic residue of 1 to 4 carbon atoms.
Backaround of the InventiQn In the prior art, a preference has of~en been made for carrying out such biotransformations with a small alkyl residue ~for R'. Thus, in EP-A-019662S, where 2-halopropionic acids are resolved by Candida cylindracea lipase (CCL) in a two-phase system, R' is de~ined as C1-C~
alkyl. Moreover, later work with this enzyme, as described by Wu et al, J. Am. Chem. Soc. (1990~ 112, 1990-5, concentrates on using the methyl ester for resolution of arylpropionic acids. The enzyme is purified, by additidn of sodium deoxycholate to the enzyme solution . and subsequent precipitation of the protein in 1:1 ethanol/diethyl ether.
This preference, for esters of ketoprofen at least, when using a crude preparation of CCL, is supported by the Table, below: enantiospecificity, as determined by the enantiomeric excess (ee) of the acid formed, declines with chain length from R'=methyl to R'=n-propyl.
Cambou and Klibanov, Appl. Biochem. Biotechnol. (1984) ~:255-60, report that CCL hydrolysis is selective for octyl 35 2-chloropropionate but not for the methyl e~ter. However, the failure of this methyl ester to exhibit SU~3STITUTE SHE~T
211600~
enantiospecificity is considered to be due to its water-solubility, causing it not to form an interface.
SummarY of the Invention As also shown in the Table, it has now surprisingly been found that when the esters are derived from increasingly longer chain alcohols, the ee subsequently increases to a higher figure thian that obtainable with the methyl ester, of approximately 98% at R'-C~ and C10 n-alkyl.
According to the present invention, the reaction illustrated above is conducted using crude (or partially-purified) enzyme, and R' has more than 4, e.g. 5, 6 or 7 to 15 to 20 C atoms. Subsequent work with purified enzyme showed that high ee was achieved whatever the chain length, but the purification adds to the overall cost.
DescriDtion of the Invention CCL has been identified as the most promising en2yme for enantiosspecific hydrolysis of racemic esters of ketoprofen. This enzyme gives the fastest rate and, unlike the majority of other active lipases, preferentially hydrolyses the S-ester, enabling simple purification of S-ketoprofen.
It appears that contaminating activities in crude CCL
do not carry out the non-selective hydrolysis with esters of long-chain alcohols. Thus, there is advantage in using a long chain ester to enable the economy of using a crude or only partially pure enzyme. More particularly, the fact that, say, octyl Xetoprofen can be used as a substrate with partially purified enzyme producing S-ketoprofen with ee of greater than 95% allows the development of a commercial process.
The following Examples illustrate the invention or are comparative.
Exam~les CCL is used as the biocatalyst to resolve racemic mixtures of various alkyl esters of ketoprofen; S-ketoprofen is formed. The same reaction conditions are used, i.e. lO ml of O.l M potassium phosphate, pH 7.5 plus SUBSTITUTE ~;HEET
W093tO4190 211 6 0 D ~ PCT/EP92/01896 2 ml cyclohexane, lOO mg alkyl ketoprofen, 50 mg enzyme, 30C. Results are given in the Table.
The CCL is used in crude form, or after a three-step purification, comprising water extraction, filtra-tion and column separation, as follows: The enzyme wasresuspended at 50 mg/ml in deionised water. After stirring at room temperature for 30 minutes, the inso-luble material was spun out. The supernatant was dia-filtered against lO volumes of McIlvaine's buffer (20 mM K2HP04 + 10 mM citric acid, pH 3.7) at room tempera-ture. Following diafiltration, the enzyme solution was concentrated to l/5 of its original volume. The enzyme solution was bonded onto an AP-sephadex C 50 column (20 ml enzyme solution: 20 ml of gel) equilibrated with McIlvaine's buffer. The column was washed with McIlvaine's buffer + 20 mM NaCl. After the first peak had eluted and the absorbance (at 280 nm) had returned to baseline, McIlvaine's buffer + 200 mM NaCl was used to elute a second protein peak.
The final step of purification yielded two activi-ties. The protein eluted at a higher salt concentration was foun~ to be highly enantiospecific.
The respective properties of the CCL biocatalysts were:
Crude Purified _ _ _ _ _EAzyme Enzyme Mass 50 g 2.l g Powder Activity 150 U/mg 680 U/mg Yield (lOO~) 19%
E (enantiospecifity ratio of enzyme)B 15 >200 A - Assayed using olive oil as substrate, 37C, pH 7.5.
B - lOO ml O.l M ketoprofen: pH 6.5, 2 ml cyclohexane, lOO mg methyl ketoprofen, 30,000 U CCL, 30C.
Table: Enantiomeric excess values~~) of S-ketoprofen __ by Candida cvlindracea lipase hydrolysis of esters from various alcohols.
SUBSTITUTE SHEET
~ _ . .
n-alcohols Usinq crudeUsing enzyme no . carbon enzyme purif ied on a SP
atoms Sephadex gel column ee c E ee c E
1 75_0.57 39 99 0.48 >200_ 2 540.43 5 3 _ 340.45 _ 3 4 700.44 10 I . , , , I
_ 5 890. 33 26 _ _ I -_ I
1 6 920. 27 33 _ I 7 97_ 0. 28 95 . _ -- _ 8 98o. 32 136 >99 0 . 23 >200 I _. ., __ . .
980. 18 127 ~ _ .
1 18 95 0. 16 43 - _ SUBSTITUTE SHEET
Claims (2)
1. A process for preparing predominantly the S-enantiomer of ketoprofen by biotransformation, using crude preparations of Candida Cylindracea lipase, of a racemic ester of ketoprofen, characterized in that the ester is derived from an alcohol of formula ROH, wherein R1 is an alkyl group having from 4 to 20 carbon atoms with the proviso that R1 is not n-hexyl.
2. A process according to claim 1. wherein the alcohol has 8 to 10 carbon atoms.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919118150A GB9118150D0 (en) | 1991-08-22 | 1991-08-22 | Arylalkanoic acid resolution |
| GB9118150.3 | 1991-08-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2116004A1 true CA2116004A1 (en) | 1993-03-04 |
Family
ID=10700382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2116004 Abandoned CA2116004A1 (en) | 1991-08-22 | 1992-08-19 | Arylalkanoic acid resolution |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0668925A1 (en) |
| JP (1) | JPH06510184A (en) |
| AU (1) | AU663110B2 (en) |
| CA (1) | CA2116004A1 (en) |
| GB (1) | GB9118150D0 (en) |
| WO (1) | WO1993004190A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9304351D0 (en) * | 1993-03-03 | 1993-04-21 | Chiros Ltd | Arylalkanoic acid resolution and microorganisms for use therein |
| US5912164A (en) * | 1993-03-03 | 1999-06-15 | Laboratorios Menarini S.A. | Stereoselective hydrolysis of chiral carboxylic acid esters using esterase from ophiostoma or ceratocystis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR880007428A (en) * | 1985-12-20 | 1988-08-27 | 존 알. 파이크 | Method for preparing (S) -α-methyl aryl acetic acid |
| US5108916A (en) * | 1989-06-05 | 1992-04-28 | Rhone-Poulenc Rorer, S.A. | Process for stereoselectively hydrolyzing, transesterifying or esterifying with immobilized isozyme of lipase from candida rugosa |
| WO1991013163A1 (en) * | 1990-02-26 | 1991-09-05 | Rhone-Poulenc Inc. | Stereospecific resolution by hydrolysis of esters of 2-arylpropionic acids by liver enzymes |
-
1991
- 1991-08-22 GB GB919118150A patent/GB9118150D0/en active Pending
-
1992
- 1992-08-19 AU AU24772/92A patent/AU663110B2/en not_active Ceased
- 1992-08-19 EP EP92918132A patent/EP0668925A1/en not_active Withdrawn
- 1992-08-19 WO PCT/EP1992/001896 patent/WO1993004190A1/en not_active Ceased
- 1992-08-19 CA CA 2116004 patent/CA2116004A1/en not_active Abandoned
- 1992-08-19 JP JP5504119A patent/JPH06510184A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0668925A1 (en) | 1995-08-30 |
| AU663110B2 (en) | 1995-09-28 |
| GB9118150D0 (en) | 1991-10-09 |
| JPH06510184A (en) | 1994-11-17 |
| AU2477292A (en) | 1993-03-16 |
| WO1993004190A1 (en) | 1993-03-04 |
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| Date | Code | Title | Description |
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| FZDE | Dead |