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Facile Access to Chiral Alcohols with Pharmaceutical Relevance Using a Ketoreductase Newly Mined from Pichia guilliermondi
  • ISSN号:1001-604X
  • 期刊名称:《中国化学:英文版》
  • 时间:0
  • 分类:TQ223.1[化学工程—有机化工] O622.4[理学—有机化学;理学—化学]
  • 作者机构:[1]Laboratory of Biocatalysis and Synthetic Biotechnology, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
  • 相关基金:This work was financially supported by the National Natural Science Foundation of China (No 21276082), Ministry of Science and Technology, P. R. China (No.2011CB710800), China National Special Fund for State Key Laboratory of Bioreactor Engineering (No. 2060204).
中文摘要:

与另外的功能的组一起的 Chiral 第二等的白酒经常为药品作为重要、珍贵的 synthons 被要求,农业并且另外的好化学药品。与环境地良性的反应条件,宽广反应范围,和高 stereoselectivity 的优点, prochiral 酉同类的 biocatalytic 减小在光学地活跃的白酒的合成提供重要潜力。从 Pichia guilliermondii NRRL Y-324 的 CmCR 相应羰基 reductase 是成功地 overexpressed。底层侧面描述揭示了它的宽广底层特性,盖住芳基酉同类,脂肪族的酉同类和 ketoesters。而且,许多酉同类底层被净化的酶不均匀地减少与一另外 NADPH 新生系统。减小系统展出了优秀 enantioselectivity (>99% ee ) 在所有芳香的酉同类和 ketoesters 的减小,除了 2-bromoacetophenone (93.5% ee ) 。六个酉同类的半准备的减小与高 enantioselectivity 被完成(>99% ee ) 并且隔离收益(>80%) 在 12 h 以内。这研究在 chiral 白酒 enantiomers 的不对称的合成为这酶的进一步的申请提供有用指导。

英文摘要:

Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones of- fers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y-324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (~ 99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2-bromoacetophenone (93.5% ee). Semi-preparative reduction of six ketones was achieved with high enantioselectivity (〉99% ee) and isolation yields (〉80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers.

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期刊信息
  • 《中国化学:英文版》
  • 主管单位:
  • 主办单位:中国化学会
  • 主编:
  • 地址:上海市枫林路354号中科院上海有机化学研究所
  • 邮编:200032
  • 邮箱:
  • 电话:021-54925243
  • 国际标准刊号:ISSN:1001-604X
  • 国内统一刊号:ISSN:31-1547/O6
  • 邮发代号:4-646
  • 获奖情况:
  • 中国期刊方阵“双高”期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,美国科学引文索引(扩展库),日本日本科学技术振兴机构数据库,英国英国皇家化学学会文摘
  • 被引量:175