Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase
Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase
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DOI：
10.1002/cctc.201701484
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发表时间：
2018-02-07
期刊：
影响因子：
4.5
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
--
作者：
Aleku, Godwin A.;Mangas-Sanchez, Juan;Turner, Nicholas J.
将来自Aspergilluscaureus的NADP（H）依赖性还原性氨酶（AspRedAm）与NADPH氧化酶（NOX）组合以开发氧化还原系统，其氧化辅因子。AspRedAm-NOX系统最初应用于各种外消旋仲胺和伯胺的动力学拆分，以产生对映体过量（ee）值高达99%的S-构型胺。向该系统中加入氨硼烷使得能够有效地对外消旋胺（包括药物雷沙吉兰和天然产物salsolidine）进行去外消旋化，转化率高达>98%和>99%ee。此外，通过使用AspRedAm W210 A变体，可以产生相反的R对映异构体，其效率与野生型AspRedAm相当或甚至更好。
The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99%. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98% and >99%ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.