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1. 发明授权

US06548293B1 Enzymatic process for the resolution of enantiomeric mixtures of &bgr;-lactams 有权
公开(公告)号：US06548293B1
公开(公告)日：2003-04-15
申请号：US09688852
申请日：2000-10-16
申请人： Robert A. Holton , Phong Vu
发明人： Robert A. Holton , Phong Vu
IPC分类号： C12P4100
CPC分类号： C07D401/04 , C07B2200/07 , C07D205/08 , C07D405/04 , C07D409/04 , C12P17/16 , C12P41/001
摘要： A process for the resolution of an enantiomeric mixture of &bgr;-lactams containing an ester, the process comprising selectively hydrolyzing the ester of one of the enantiomers by combining the mixture with homogenized liver.

2. 发明授权

US06399339B1 Method for the enantioselective reduction of 3,5-dioxocarboxylic acids, their salts and their esters 失效
标题翻译： 3,5-二氧代羧酸，其盐及其酯的对映选择性还原方法
公开(公告)号：US06399339B1
公开(公告)日：2002-06-04
申请号：US09857298
申请日：2001-07-10
申请人： Michael Wolberg , Michael Müller , Werner Hummel
发明人： Michael Wolberg , Michael Müller , Werner Hummel
IPC分类号： C12P4100
CPC分类号： C12P7/62 , C12P41/002
摘要： The invention relates to a method for the enantioselective reduction of 3,5-dioxocarboxylic acid derivatives and their syntheses. According to the invention, compounds of formula (4) are reacted with an alcohol dehydrogenase which preferably stems from Lactobacillus brevis and which is recombinantly over-expressed in Escherichia coli, in the presence of NADPH. The keto group in position 5 is enantioselectively reduced during this reaction. The keto group in position 3 can also be specifically syn- or anti-reduced in a further step by means of chemical or enzymatic reactions.
摘要翻译：本发明涉及3,5-二氧代羧酸衍生物的对映选择性还原方法及其合成。根据本发明，式（4）的化合物与醇脱氢酶反应，其优选来源于短乳杆菌，并且在NADPH存在下在大肠杆菌中重组过表达。在该反应期间，位置5的酮基被对映选择性还原。位置3中的酮基也可以通过化学或酶反应在另外的步骤中特异性地合成或抗还原。

3. 发明授权

US06387692B1 Process for the preparation of optically active amines 失效
标题翻译：光学活性胺的制备方法
公开(公告)号：US06387692B1
公开(公告)日：2002-05-14
申请号：US09077581
申请日：1998-06-01
申请人： Uwe Stelzer , Claus Dreisbach
发明人： Uwe Stelzer , Claus Dreisbach
IPC分类号： C12P4100
CPC分类号： C12P41/007 , C07C235/06
摘要： Process for preparing optically (S) and (R) active amines of the formula (I*) comprising reacting racemic amines corresponding to formula (I*) with esters of the formula: in the presence of lipase from Candida antarctica, and separating the (S)-amine directly from the resulting mixture, and separating the (R)-amine indirectly from the resulting mixture by reacting the acylated (R)-amine therein, which has the formula: with acid or base, wherein all the formula above, the variables are as defined herein. Certain precursors of the formula (III) are also disclosed.
摘要翻译：制备式（I *）的光学（S）和（R）活性胺的方法，包括使式（I *）的外消旋胺与下式的酯反应：在南极假丝酵母的脂肪酶存在下，将 S） - 胺，并且通过使其具有下式的酰化（R） - 胺与酸或碱反应，从而将所得到的混合物间接分离（R） - 胺，其中所有上式，变量如本文所定义。还公开了式（III）的某些前体。

4. 发明授权

US06204050B1 Producing diastereomers of 4-hydroxyproline using 4-hp epimerase from Serratia marcescens or Acinetobacter baumanni 失效
标题翻译：使用来自粘质沙雷氏菌或鲍氏不动杆菌的4-hp差向异构酶生产4-羟脯氨酸的非对映异构体
公开(公告)号：US06204050B1
公开(公告)日：2001-03-20
申请号：US09356838
申请日：1999-07-19
申请人： Robert Dicosimo , Susan K. Fager , John E. Gavagan
发明人： Robert Dicosimo , Susan K. Fager , John E. Gavagan
IPC分类号： C12P4100
CPC分类号： C12R1/43 , C12N9/90 , C12P13/24 , C12R1/01
摘要： The present invention relates to two novel microorganisms, Acinetobacter baumanni WT-50/50-4A (ATCC 202144) and Serratia marcescens WT-L-4A1(RED) (ATCC 202145) characterized by 4-hydroxyproline epimerase activity. The compounds trans-4-hydroxy-L-proline (THLP) or cis-4-hydroxy-D-proline (CHDP) are converted with this epimerase activity to a mixture of THLP and CHDP. Additionally, the compounds trans-4-hydroxy-D-proline (THDP) or cis-4-hydroxy-L-proline (CHLP) are converted with this epimerase activity to a mixture of THDP and CHLP.
摘要翻译：本发明涉及以4-羟基脯氨酸差向异构酶活性为特征的两种新型微生物鲍氏不动杆菌WT-50 / 50-4A（ATCC 202144）和粘质沙雷氏菌WT-L-4A1（RED）（ATCC 202145）。化合物反式-4-羟基-L-脯氨酸（THLP）或顺式-4-羟基-D-脯氨酸（CHDP）用该差向异构酶活性转化成THLP和CHDP的混合物。此外，反式-4-羟基-D-脯氨酸（THDP）或顺式-4-羟基-L-脯氨酸（CHLP）的化合物用该差向异构酶活性转化成THDP和CHLP的混合物。

5. 发明授权

US06800477B2 Stereoselective reduction of substituted acetophenone 有权
标题翻译：取代苯乙酮的立体选择性还原
公开(公告)号：US06800477B2
公开(公告)日：2004-10-05
申请号：US10092263
申请日：2002-03-06
申请人： Ramesh Patel , Animesh Goswami , Linda N. Chu , Venkata B. Nanduri , Steven L. Goldberg , Robert M. Johnston , Mary Jo Donovan , K. David Mirfakhrae
发明人： Ramesh Patel , Animesh Goswami , Linda N. Chu , Venkata B. Nanduri , Steven L. Goldberg , Robert M. Johnston , Mary Jo Donovan , K. David Mirfakhrae
IPC分类号： C12P4100
CPC分类号： C12P7/22 , Y10S435/911 , Y10S435/938
摘要： The present invention is directed to novel stereoselective processes for the preparation of (S)-1-arylethanols by the reduction of the corresponding keto group containing compounds by microorganisms. (S)-1-arylethanols are useful as intermediates in the synthesis of compounds that are inhibitors of &ggr;-secretase useful in the treatment of Alzheimer's disease.
摘要翻译：本发明涉及通过微生物还原相应的含有酮基的化合物来制备（S）-1-芳基乙醇的新的立体选择性方法。（S）-1-芳基乙醇可用作合成作为可用于治疗阿尔茨海默病的γ-分泌酶的抑制剂的化合物的中间体。

6. 发明授权

US06395535B1 Optical resolution of 4-halogeno-3-alkanoyloxy-butyronitrile 失效
标题翻译： 4-卤代-3-烷酰氧基 - 丁腈的光学拆分
公开(公告)号：US06395535B1
公开(公告)日：2002-05-28
申请号：US09542252
申请日：2000-04-03
申请人： Naoya Kasai , Toshio Suzuki , Hideaki Idogaki , Miki Hatada , Motoko Takeuchi
发明人： Naoya Kasai , Toshio Suzuki , Hideaki Idogaki , Miki Hatada , Motoko Takeuchi
IPC分类号： C12P4100
CPC分类号： C12P41/002
摘要： A process for preparation of optically active 4-halogeno-3-hydoxybutyronitrile and 4-halogeno-3-alkanoyloxybutyronitrile, which are simply and economically prepared by reacting a racemic 4-halogeno-3-alkanoyloxybutyronitrile with a microorganism such as a strain of the genus Pseudomonas or the genus Enterobacter, which has the activity stereoselectively hydrolyzing the ester portion, its culture broth or an enzyme(s) derived from the microorganism or an enzyme preparation such as a lipase preparation.
摘要翻译：制备光学活性4-卤代-3-羟基丁腈和4-卤代-3-烷酰氧基丁腈的方法，其通过外消旋4-卤代-3-烷酰氧基丁腈与微生物如属的菌株反应而简单且经济地制备假单胞菌属或肠杆菌属，其活性立体选择性地水解酯部分，其培养液或源自微生物的酶或酶制剂如脂肪酶制剂。

7. 发明授权

US06368850B1 Process for the preparation of amino alcohols and derivatives thereof 失效
标题翻译：氨基醇及其衍生物的制备方法
公开(公告)号：US06368850B1
公开(公告)日：2002-04-09
申请号：US09194626
申请日：1999-05-21
申请人： Christine Bernegger-Egli , Olwen M. Birch , Pierre Bossard , Walter Brieden , Frank Brux , Knut Burgdorf , Laurent Duc , Kay-Sarah Etter , Yves Guggisberg , Martin Sauter , Eva Maria Urban
发明人： Christine Bernegger-Egli , Olwen M. Birch , Pierre Bossard , Walter Brieden , Frank Brux , Knut Burgdorf , Laurent Duc , Kay-Sarah Etter , Yves Guggisberg , Martin Sauter , Eva Maria Urban
IPC分类号： C12P4100
CPC分类号： C12P13/001 , C07C215/42 , C07D209/52 , C12N9/80 , C12P13/02 , C12P41/007 , C12R1/01
摘要： The invention relates to a novel process for the preparation of (1R,4S)- or (1S,4R)-1-amino-4-(hydroxymethyl)-2-cyclopentene of the formulae and/or of (1S,4R)- or (1R,4S)-amino alcohol derivatives of the general formulae and to novel microorganisms which are able to utilize a cyclopentene derivative of the general formula as sole nitrogen source, as sole carbon source or as sole carbon and nitrogen source. The invention further relates to enzyme extracts and enzymes having N-acetylamino-alcohol hydrolase activity obtainable from these microorganisms.
摘要翻译：本发明涉及式（1R，4S） - 或（1S，4R）-1-氨基-4-（羟甲基）-2-环戊烯的新颖方法和/或（1S，4R） - 或（1R，4S） - 氨基醇衍生物，以及能够利用通式为唯一氮源的环戊烯衍生物作为唯一碳源或唯一碳源和氮源的新型微生物。本发明还涉及酶提取物和具有从这些微生物获得的N-乙酰氨基 - 醇水解酶活性的酶。

8. 发明授权

US06737264B1 Method for purifying and isolating (2s,3s)- or (2r,3s)-halohydrin derivatives 失效
标题翻译：纯化和分离（2s，3s） - 或（2r，3s） - 卤代醇衍生物的方法
公开(公告)号：US06737264B1
公开(公告)日：2004-05-18
申请号：US09869297
申请日：2001-11-02
申请人： Katsuji Maehara , Shigeru Kawano , Makoto Yamaguchi , Yasuyoshi Ueda
发明人： Katsuji Maehara , Shigeru Kawano , Makoto Yamaguchi , Yasuyoshi Ueda
IPC分类号： C12P4100
CPC分类号： C12P41/002 , C07C269/08 , C12P13/02 , C07C271/16
摘要： The present invention has for its object to provide a practical method for the purification and isolation on a commercial scale of said compound (1) or compound (2) in good yield and with high quality. The present invention provides a purification/isolation method of a (2S,3S)-1-halo-2-hydroxy-3-N-(tert-butoxycarbonyl)amino-4-phenylbutane (1) or a (2R,3S)-1-halo-2-hydroxy-3-N-(tert-butoxycarbonyl)amino-4-phenylbutane (2) which comprises, for the purpose of removing contaminant impurity from a mixture containing at least one of said compounds (1) and (2), causing the objective compound (1) or compound (2) to be crystallized in the presence of a solvent comprised of a hydrocarbon solvent and then collecting the obtained crystals.
摘要翻译：本发明的目的是提供一种以高产率和高质量在商业规模上纯化和分离所述化合物（1）或化合物（2）的实用方法。本发明提供了一种纯化/分离方法（2S，3S）-1-卤代-2-羟基-3-N-（叔丁氧基羰基）氨基-4-苯基丁烷（1）或（2R，3S）-1-卤代-2-羟基-3- N-（叔丁氧基羰基）氨基-4-苯基丁烷（2），其包含为了从含有至少一种所述化合物（1）和（2）的混合物除去污染物杂质的目的化合物（1）或化合物（2）在由烃溶剂组成的溶剂的存在下结晶，然后收集所获得的晶体。

9. 发明授权

US06475773B2 Method for preparing chiral esters 失效
标题翻译：手性酯的制备方法
公开(公告)号：US06475773B2
公开(公告)日：2002-11-05
申请号：US09726412
申请日：2000-12-01
申请人： Jai Wook Park , Mahn-Joo Kim , Jeong Hwan Koh , Hyun Min Jung
发明人： Jai Wook Park , Mahn-Joo Kim , Jeong Hwan Koh , Hyun Min Jung
IPC分类号： C12P4100
CPC分类号： C12P41/003 , C12P7/62
摘要： The present invention relates to a method for preparing a chiral ester and more particularly, the method for preparing an optically pure chiral ester from an alkenyl ester at a high yield by mixing and reacting: an alkenyl ester; a ruthenium complex to activate reduction reaction of said alkenyl ester and racemization; a lipase to acylate selectively one of enantiomers of said alkenyl ester; and a reducing agent to supply a hydride to said ruthenium complex. Said optically pure chiral ester of the present invention can be prepared by one-step synthesis from various types of alkenyl esters at a high yield.
摘要翻译：本发明涉及一种制备手性酯的方法，更具体地说，涉及通过混合和反应从链烯基酯以高产率制备光学纯手性酯的方法：烯基酯; 用于活化所述烯基酯的还原反应的钌络合物和外消旋化;选择性地将所述烯基酯的对映异构体中的一种酰化的脂肪酶; 和还原剂，以向所述钌络合物供应氢化物。本发明的所述光学纯手性酯可以通过以高收率从各种类型的烯基酯进行一步合成来制备。

10. 发明授权

US06365399B1 Process for producing carboxylic acid isomer using Nocardia diaphanozonaria or Saccharopolyspora hirsuta 失效
标题翻译：使用诺卡氏菌（Nocardia diaphanozonaria）或酿酒酵母（Saccharopolyspora hirsuta）生产羧酸异构体的方法
公开(公告)号：US06365399B1
公开(公告)日：2002-04-02
申请号：US09625323
申请日：2000-07-25
申请人： Yoshiki Takashima , Yuko Kobayashi
发明人： Yoshiki Takashima , Yuko Kobayashi
IPC分类号： C12P4100
CPC分类号： C12P7/40 , C12N9/90 , C12P17/00 , C12P41/00
摘要： The present invention provides a process for producing a carboxylic acid isomer B represented by the general formula (2): (wherein, L is a C6 to C14 aryl group which may optionally been substituted, C4 to C12 heteroaryl group which may optionally been substituted, C6 to C14 aryloxy group which may optionally been substituted or C4 to C12 heteroaryloxy group which may optionally been substituted, and M is an C1 to C3 alkyl group.), which comprises: allowing a carboxylic acid isomer A represented by the general formula (1): (wherein, L and M have meanings as defined above.) to contact with a microbiological material having an ability to convert the carboxylic acid isomer A(1) into the carboxylic acid isomer B(2), and the like. According to the present invention, the carboxylic acid isomer B(2) useful as an intermediate of medicines, agricultural chemicals and like can be produced efficiently.
摘要翻译：本发明提供一种由通式（2）表示的羧酸异构体B的制备方法：其中，L为任选被取代的C 6〜C 14芳基，可任选被取代的C 4〜C 12杂芳基，可任选被取代的C 6至C 14芳氧基或可任选被取代的C 4至C 12杂芳氧基，M为C 1至C 3烷基），其包括：使由通式（1）表示的羧酸异构体A ）（其中，L和M具有如上定义的含义）与具有将羧酸异构体A（1）转化成羧酸异构体B（2）的能力的微生物材料接触等。根据本发明，可有效地制备可用作药物，农药等的中间体的羧酸异构体B（2）。

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