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Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen

文献类型：期刊论文

作者Duan YiTao1,2; Yao PeiYuan1,2; Ren Jie1,2; Han Chao1,2,3; Li Qian1,2; Yuan Jing1,2; Feng JinHui1,2; Wu QiaQing1,2; Zhu DunMing1,2
刊名SCIENCE CHINA-CHEMISTRY
出版日期2014-08-01
卷号57期号:8页码:1164-1171
关键词enzymatic desymmetrization nitrilases (S)-Pregabalin (R)-Baclofen
英文摘要Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access (S)-Pregabalin and (R)-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles (1a) or 3-(4'-chlorophenyl)glutaronitriles (1b) as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of 1a and 1b to form optically active 3-(cyanomethyl)-5-methylhexanoic acid (2a) and 3-(4'-chlorophenyl)-4-cyanobutanoic acid (2b) with high enantiomeric excesse (ee), respectively. This cannot be achieved using traditional chemical hydrolysis. Among them, AtNIT3 generated (R)-2b, whereas BjNIT6402 and HsNIT produced the opposite (S)-enantiomer with high conversions and ee values. Not only the nitrilases showed different activities and stereoselectivities toward these 3-substituted glutaronitriles, the 3-substituent of the substrates also exerted great effect on the enzyme activity and stereoselectivity. (S)-2a and (S)-2b were prepared with high yields and ee values using BjNIT6402 and HsNIT as the biocatalysts, respectively. A straightforward Curtius rearrangement of (S)-2a and (S)-2b, followed by the acidic hydrolysis, afforded (S)-Pregabalin and (R)-Baclofen. This offers a new platform methodology for the synthesis of optically active beta-substituted gamma-amino acids of pharmaceutical importance.
WOS标题词Science & Technology ; Physical Sciences
类目[WOS]Chemistry, Multidisciplinary
研究领域[WOS]Chemistry
关键词[WOS]ARABIDOPSIS-THALIANA ; SELECTIVE HYDROLYSIS ; MICHAEL ADDITION ; GENE CLONING ; ACID ; PREGABALIN ; DINITRILES
收录类别SCI ; CCR
语种英语
WOS记录号WOS:000340084700018
公开日期2015-01-24
源URL[http://124.16.173.210/handle/311007/686]  
专题天津工业生物技术研究所_生物催化与绿色化工 朱敦明_期刊论文
作者单位1.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Engn Lab Ind Enzymes, Tianjin 300308, Peoples R China
2.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin Engn Ctr Biocatalyt Technol, Tianjin 300308, Peoples R China
3.Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin 300457, Peoples R China
推荐引用方式
GB/T 7714		 Duan YiTao,Yao PeiYuan,Ren Jie,et al. Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen[J]. SCIENCE CHINA-CHEMISTRY,2014,57(8):1164-1171.
APA Duan YiTao.,Yao PeiYuan.,Ren Jie.,Han Chao.,Li Qian.,...&Zhu DunMing.(2014).Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen.SCIENCE CHINA-CHEMISTRY,57(8),1164-1171.
MLA Duan YiTao,et al."Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen".SCIENCE CHINA-CHEMISTRY 57.8(2014):1164-1171.

入库方式： OAI收割

来源：天津工业生物技术研究所

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