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转氨酶介导的对映体纯的类药物1-(3',4'-二取代苯基)丙-2-胺的合成。

Transaminase-mediated synthesis of enantiopure drug-like 1-(3',4'-disubstituted phenyl)propan-2-amines.

作者信息

Lakó Ágnes, Molnár Zsófia, Mendonça Ricardo, Poppe László

机构信息

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary

Hovione Farmaciência, S.A., Campus do Lumiar Edifício R, Estrada do Paço do Lumiar 1649-038 Lisboa Portugal.

出版信息

RSC Adv. 2020 Nov 10;10(67):40894-40903. doi: 10.1039/d0ra08134e. eCollection 2020 Nov 9.

DOI:10.1039/d0ra08134e
PMID:35519186
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9057730/
Abstract

Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with ()-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the ()-enantiomers could be produced with 88-89% conversion and >99% ee, while the ()-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee.

摘要

转氨酶（TAs）为从手性前体酮直接合成具有药学相关性的二取代1-苯基丙-2-胺衍生物提供了一种环境友好且经济可行的方法。在本研究中，我们报道了具有（）-转氨酶活性的固定化全细胞生物催化剂在新型二取代1-苯基丙-2-胺合成中的应用。经过不对称合成优化后，（）-对映体的转化率可达88-89%，对映体过量值（ee）>99%，而在动力学拆分中，（）-对映体可作为相应外消旋胺的未反应部分选择性获得，转化率>48%，ee>95%。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6599/9057730/744524e4a700/d0ra08134e-f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6599/9057730/744524e4a700/d0ra08134e-f6.jpg

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