EP1440158A1 - Verfahren zur herstellung von (r)- und (s)-8-chlor-6-hydroxy-octansäurealkylestern durch enzymatische reduktion - Google Patents
Verfahren zur herstellung von (r)- und (s)-8-chlor-6-hydroxy-octansäurealkylestern durch enzymatische reduktionInfo
- Publication number
- EP1440158A1 EP1440158A1 EP02779483A EP02779483A EP1440158A1 EP 1440158 A1 EP1440158 A1 EP 1440158A1 EP 02779483 A EP02779483 A EP 02779483A EP 02779483 A EP02779483 A EP 02779483A EP 1440158 A1 EP1440158 A1 EP 1440158A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- chloro
- acid alkyl
- hydroxy
- alkyl esters
- octanoic acid
- 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.)
- Withdrawn
Links
- 230000009467 reduction Effects 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000002255 enzymatic effect Effects 0.000 title claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- 108010021809 Alcohol dehydrogenase Proteins 0.000 claims abstract description 14
- 102000007698 Alcohol dehydrogenase Human genes 0.000 claims abstract description 13
- 230000008929 regeneration Effects 0.000 claims abstract description 6
- 238000011069 regeneration method Methods 0.000 claims abstract description 6
- 240000001929 Lactobacillus brevis Species 0.000 claims abstract description 5
- 235000013957 Lactobacillus brevis Nutrition 0.000 claims abstract description 5
- 241000186339 Thermoanaerobacter Species 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 9
- 102000005751 Alcohol Oxidoreductases Human genes 0.000 claims description 6
- 108010031132 Alcohol Oxidoreductases Proteins 0.000 claims description 6
- AGBQKNBQESQNJD-ZETCQYMHSA-N (S)-lipoic acid Chemical compound OC(=O)CCCC[C@H]1CCSS1 AGBQKNBQESQNJD-ZETCQYMHSA-N 0.000 claims description 4
- ULYONBAOIMCNEH-HNNXBMFYSA-N (3s)-3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1h-indol-2-one Chemical compound COC1=CC=C(Cl)C=C1[C@@]1(F)C2=CC=C(C(F)(F)F)C=C2NC1=O ULYONBAOIMCNEH-HNNXBMFYSA-N 0.000 abstract 1
- WXPREQDMOKXUIM-ZETCQYMHSA-N (6s)-8-chloro-6-hydroxyoctanoic acid Chemical class ClCC[C@@H](O)CCCCC(O)=O WXPREQDMOKXUIM-ZETCQYMHSA-N 0.000 abstract 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 235000019136 lipoic acid Nutrition 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 4
- -1 keto compound Chemical class 0.000 description 4
- 229960002663 thioctic acid Drugs 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000011942 biocatalyst Substances 0.000 description 3
- 230000036983 biotransformation Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 150000003333 secondary alcohols Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- LYJQMHVYFFZQGY-UHFFFAOYSA-N 1,5-dichloropentan-3-one Chemical compound ClCCC(=O)CCCl LYJQMHVYFFZQGY-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 108090000698 Formate Dehydrogenases Proteins 0.000 description 2
- 241000186660 Lactobacillus Species 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 229940039696 lactobacillus Drugs 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- WXPREQDMOKXUIM-UHFFFAOYSA-N 8-chloro-6-hydroxyoctanoic acid Chemical compound ClCCC(O)CCCCC(O)=O WXPREQDMOKXUIM-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- YPZRHBJKEMOYQH-UYBVJOGSSA-N FADH2 Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C(NC(=O)NC2=O)=C2NC2=C1C=C(C)C(C)=C2 YPZRHBJKEMOYQH-UYBVJOGSSA-N 0.000 description 1
- 206010016275 Fear Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000316848 Rhodococcus <scale insect> Species 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 230000002210 biocatalytic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CFBWDJXULUFEQI-UHFFFAOYSA-N ethyl 3-chloro-4-oxooctanoate Chemical compound CCCCC(=O)C(Cl)CC(=O)OCC CFBWDJXULUFEQI-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- MJGRFAJZJNWXBR-MRVPVSSYSA-N methyl (6r)-8-chloro-6-hydroxyoctanoate Chemical compound COC(=O)CCCC[C@@H](O)CCCl MJGRFAJZJNWXBR-MRVPVSSYSA-N 0.000 description 1
- QYRJJEJBDHZFKD-UHFFFAOYSA-N methyl 8-chloro-6-oxooctanoate Chemical compound COC(=O)CCCCC(=O)CCCl QYRJJEJBDHZFKD-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
-
- 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
- C12P7/42—Hydroxy-carboxylic acids
-
- 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
- C12P7/62—Carboxylic acid esters
Definitions
- the invention relates to a ner process for the preparation of (R) - and (S) -8-chloro-6-hydroxy-octanoic acid alkyl esters of the formula I by enzymatic reduction of a suitable prochiral keto compound.
- R alkyl
- the -liponic acid is synthesized on an industrial scale starting from 8-chloro-6-oxo-octanoic acid alkyl esters, which are converted into 8-chloro-6-hydroxy-octanoic acid alkyl ester by ⁇ aBH 4 reduction (Lit .: Kleemann and Engel, Pharmaceutical Substances, 3rd Ed., Thieme, 1999, page 1860).
- the racemic ⁇ -lipoic acid is obtained in high overall yield by a subsequent three-step synthesis sequence.
- the synthesis of the pure enantiomers for targeted pharmaceutical use is also of great importance (see, for example, EP 04 27 247).
- the object of the invention was therefore to provide a process for the production of certain intermediates for the production of the (R) - and (S) - ⁇ -lipoic acid and the (R) - and (S) - ⁇ -lipoic acid itself, which is a production of these Compounds and intermediates with high yield and high enantiomeric purity possible.
- This object is achieved in that 8-chloro-6-oxo-octanoic acid alkyl ester is reduced enzymatically by means of alcohol dehydrogenases or carbonyl reductases. In this reaction, either the (R) or (S) -8-chloro-6-hydroxy-octanoic acid alkyl ester of the formula (R) -LT or (S) -LT specified in the claim is obtained.
- the invention is based on the knowledge that the starting ester used can be reduced in a simple and very effective manner by means of known alcohol dehydrogenases or carbonyl reductases.
- dehydrogenases could be suitable for the synthesis of chiral compounds (see, inter alia, Kragl and Kula, in Stereoselective Biotransformations, editors R. Patel, Marcel Dekker, 2000, pages 839-866.)
- the general Statements from this and similar literature references cannot, however, be transferred to complex starting compounds.
- a person skilled in the art regularly fears side reactions and a reduced enantioselectivity.
- J. Org. Chem. 66, 8682-84 shows that an 8-chloro-3-hydroxyoxanoic acid alkyl ester can be obtained by reduction from the corresponding ketone with purified carbonyl reductase and whole cells.
- EP 0 939 132 AI discloses an enzymatic reduction of 4-halogen-3-ketobutyric acid esters.
- J. Org. Chem. 63, 1102-08 (1998) describes the reduction of ethyl 3-chloro-4-keto-octanoate. From EP 0 487 986 A2 is known to obtain (3S) -3-hydroxyoctanedioic acid diester for the production of lipoic acid by reduction with baker's yeast.
- the invention is specified in claim 1 and further dependent claims.
- generally known cofactors are used, such as NAD (H), NADP (H), FADH.
- NAD (H) or NADP (H) is preferably used.
- the configuration of the 8-chloro-6-hydroxy-octanoic acid alkyl ester obtained is determined by the enzyme used.
- enantiomerically pure (R) -8-chloro-6-hydroxy-octanoic acid alkyl esters are obtained.
- the prochiral-8-chloro-6-oxo-octanoic acid alkyl esters can be obtained in a known manner (L.J. Reed et al., J. Am. Chem. Soc. 1955, 774, 416).
- cofactor regeneration systems which bring about a shift in the equilibrium of the main reaction have proven to be particularly advantageous.
- substrate-coupled cofactor regeneration can advantageously take place in the presence of an excess of a secondary alcohol (for example 2-propanol).
- enzyme-linked cofactor regeneration systems e.g. formate dehydrogenase
- FDH NAD- and NADP-dependent formate dehydrogenases
- the absolute configuration of the optical isomers of the 8-chloro-6-hydroxy-octanoic acid alkyl esters of the formula I was determined by comparing the signs of the specific optical rotation values with literature data (Gewald et al., DE 195 33 881). Furthermore, the relative contents of the optical isomers of the 8-chloro-6-hydroxy-octanoic acid alkyl esters of the formula I were determined by GC on columns with a chiral phase with a detection limit of ⁇ 0.5%.
- the present invention enables the (R) - and (S) -8-chloro-6-hydroxy-octanoic acid alkyl esters of the formula I in a simple and economical manner in high chemical and optical yield (theoretically 100% chemical and optical yield) accessible in a one-step process.
- the invention also relates to the use of the enantiomerically pure octanoic acid alkyl esters obtained in the process according to the invention for the production of (R) - or (S) - ⁇ -lipoic acid in a manner known per se.
- the chlorohydroxyctanoic acid alkyl esters are usually converted into the corresponding dichloroctanoic acid alkyl esters.
- the known lipoic acid structure is then obtained in a further reaction step by introducing sulfur.
- (S) -8-chloro-6-hydroxy-octanoic acid alkyl esters can be obtained by using, for example, Lactobacillus brevis alcohol dehydrogenase as the biocatalyst.
- the synthesis of (+) - and (-) - ⁇ -lipoic acids starting from (+) - and (-) - 8-chloro-6-hydroxy-octanoic acid alkyl esters can be carried out in accordance with the known methods of Ner. The invention is illustrated by the following example.
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (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)
- Mycology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10152113A DE10152113C1 (de) | 2001-10-23 | 2001-10-23 | Verfahren zur Herstellung von (R)- und (S)-8-Chlor-6-hydroxy-octansäurealkylestern durch enzymatische Reduktion |
| DE10152113 | 2001-10-23 | ||
| PCT/EP2002/011470 WO2003035885A1 (de) | 2001-10-23 | 2002-10-14 | Verfahren zur herstellung von (r)- und (s)-8-chlor-6-hydroxy-octansäurealkylestern durch enzymatische reduktion |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1440158A1 true EP1440158A1 (de) | 2004-07-28 |
Family
ID=7703317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02779483A Withdrawn EP1440158A1 (de) | 2001-10-23 | 2002-10-14 | Verfahren zur herstellung von (r)- und (s)-8-chlor-6-hydroxy-octansäurealkylestern durch enzymatische reduktion |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7157253B2 (enExample) |
| EP (1) | EP1440158A1 (enExample) |
| JP (1) | JP2005506091A (enExample) |
| DE (1) | DE10152113C1 (enExample) |
| WO (1) | WO2003035885A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102012017026A1 (de) | 2012-08-28 | 2014-03-06 | Forschungszentrum Jülich GmbH | Sensor für NADP(H) und Entwicklung von Alkoholdehydrogenasen |
| US10294479B2 (en) | 2015-03-04 | 2019-05-21 | East China University Of Science And Technology | Candida carbonyl reductase and method for preparing (R)-lipoic acid precursor |
| CN106083811B (zh) * | 2016-06-14 | 2019-02-05 | 苏州富士莱医药股份有限公司 | (R)-α-硫辛酸的制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4037440A1 (de) * | 1990-11-24 | 1992-05-27 | Basf Ag | Verfahren zur herstellung von (6s)-6,8-dihydroxyoctansaeureestern |
| DE19533882A1 (de) | 1995-09-13 | 1997-03-20 | Dresden Arzneimittel | Herstellung und Verwendung der reinen Enantiomere der 8-Halogen-6-hydroxyoctansäuren, ihrer Alkylester und ihrer Salze mit reinen Enantiomeren des alpha-Methylbenzylamins |
| JP4012299B2 (ja) * | 1998-02-25 | 2007-11-21 | ダイセル化学工業株式会社 | ハロゲン置換を含む光学活性アルコールの製造方法 |
| WO2002010422A1 (de) | 2000-07-27 | 2002-02-07 | Viatris Gmbh & Co. Kg | Verfahren zur enantioselektiven reduktion von 8-chlor-6-oxo-octansäurealkylestern |
| DE10056025A1 (de) * | 2000-07-27 | 2002-02-07 | Asta Medica Ag | Verfahren zur enantioselektiven Reduktion von 8-Chlor-6oxo-octansäurealkylestern |
-
2001
- 2001-10-23 DE DE10152113A patent/DE10152113C1/de not_active Withdrawn - After Issue
-
2002
- 2002-10-14 WO PCT/EP2002/011470 patent/WO2003035885A1/de not_active Ceased
- 2002-10-14 EP EP02779483A patent/EP1440158A1/de not_active Withdrawn
- 2002-10-14 JP JP2003538385A patent/JP2005506091A/ja not_active Withdrawn
- 2002-10-14 US US10/493,630 patent/US7157253B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| See references of WO03035885A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| DE10152113C1 (de) | 2003-03-06 |
| US20050032180A1 (en) | 2005-02-10 |
| JP2005506091A (ja) | 2005-03-03 |
| WO2003035885A1 (de) | 2003-05-01 |
| US7157253B2 (en) | 2007-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1196545B1 (de) | Elektronendonorsystem für enzyme und dessen anwendung bei der biochemischen umsetzung von substraten | |
| EP1832658B1 (de) | Verfahren zur Herstellung von optisch aktiven sekundären Alkoholen aus Ketonen unter Verwendung einer adsorbierten Carbonylreduktase-Aktivität | |
| EP2812439A1 (de) | Verfahren zur enzymatischen regenerierung von redoxkofaktoren | |
| WO1995008636A1 (de) | Racematspaltung primärer und sekundärer amine durch enzym-katalysierte acylierung | |
| WO2005108593A1 (de) | Verfahren zur herstellung von 2-butanol | |
| AT501928B1 (de) | Verfahren zur herstellung von chiralen alkoholen | |
| DE102004007029A1 (de) | Verfahren zur enantioselektiven Reduktion von Ketoverbindungen durch Enzyme | |
| DE3344085A1 (de) | Verfahren zur herstellung von l-carnitin und zwischenprodukte fuer das verfahren | |
| WO2006061137A1 (de) | Gdh-mutante mit verbesserter chemischer stabilität | |
| US5413921A (en) | Method of the production of (s)-gamma-halogenated-γ-hydroxybutyric acid esters | |
| DE10152113C1 (de) | Verfahren zur Herstellung von (R)- und (S)-8-Chlor-6-hydroxy-octansäurealkylestern durch enzymatische Reduktion | |
| EP0599967B1 (en) | Arylalkanoic acid resolution | |
| Akakabe et al. | Biotransformation of acetophenone with immobilized cells of carrot, tobacco and gardenia | |
| EP1307577B1 (de) | Verfahren zur enantioselektiven reduktion von 8-chlor-6-oxo-octansäurealkylestern | |
| DE69730444T2 (de) | Verfahren zur herstellung optisch aktiven n-benzyl-3-pyrrolidinols | |
| EP1829974A1 (de) | Verfahren zur Herstellung von (S)-2-Butanol und 2-Butanon aus racemischem 2-Butanol unter Verwendung einer Alkoholdehydrogenase | |
| JP3077478B2 (ja) | 微生物酵素による光学活性１，２−ジオール類およびハロゲノヒドリン類の製造法 | |
| DE60309830T2 (de) | Verfahren zur herstellung von chiralen aromatischen alpha-hydroxy-ketonen unter verwendung einer 2-hydroxy-3-oxosäure-synthase | |
| WO2008022627A2 (de) | Verfahren zur herstellung von optisch aktiven hydroxyalkylacetaten durch racematspaltung von 4-hydr0xy-2-ket0nen unter verwendung von baeyer-vi lliger monooxygenasen | |
| EP1290208B1 (en) | Method for optically resolving a racemic alpha-substituted heterocyclic carboxylic acid using enzyme | |
| EP0709464B1 (de) | Verfahren zur enzymatischen Enantiomeren-Trennung von rac-2-Oxotricyclo 2,2,1,03,5 -heptan-7-carbonsäure bzw. der -carbonsäureester | |
| JP3135740B2 (ja) | Ｒ−パントラクトンの製造法 | |
| DE102005038606A1 (de) | Verfahren zur enzymatischen Herstellung von chiralen 1-acylierten 1,2-Diolen | |
| KR20020001658A (ko) | 미생물 배양에 의한 광학 활성 1,2-디올의 제조 방법 | |
| JP3843692B2 (ja) | 光学活性ｅｎｄｏ−ノルボルネオールの製造法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20040524 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SK TR |
|
| AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO SI |
|
| RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: VIATRIS GMBH & CO. KG |
|
| RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: MEDA PHARMA GMBH & CO. KG |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
| 18W | Application withdrawn |
Effective date: 20070521 |