Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines
Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines
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DOI：
10.1016/j.bmc.2017.07.023
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
--
作者：
Herter, Susanne;Medina, Florian;Turner, Nicholas J.
针对最通用的单胺氧化酶（MAO-N）变体D5、D9和D11筛选132种外消旋手性胺（α-取代的甲基苄胺、二苯甲基胺、1，2，3，4-四氢萘胺（THN）、茚满胺、烯丙基胺和高烯丙基胺、炔丙基胺）的文库。MAO-N D9对大多数底物表现出最高的活性，并被应用于一组全面的选择的伯胺的去外消旋化。在所有情况下，实现了优异的对映体选择性（e. e. >99%），具有中等至良好的产率（55-80%）。使用MAO-N/硼烷系统对伯胺进行去外消旋化的条件使用THN作为模板进一步优化，该模板涉及底物负载、酶制剂的性质、缓冲系统、硼烷源和有机共溶剂。皇冠版权所有（C）2017由爱思唯尔有限公司发布。保留所有权利。
A library of 132 racemic chiral amines (alpha-substituted methylbenzylamines, benzhydrylamines, 1,2,3,4-tetrahydronaphthylamines (THNs), indanylamines, allylic and homoallylic amines, propargyl amines) was screened against the most versatile monoamine oxidase (MAO-N) variants D5, D9 and D11. MAO-N D9 exhibited the highest activity for most substrates and was applied to the deracemisation of a comprehensive set of selected primary amines. In all cases, excellent enantioselectivity was achieved (e.e. >99%) with moderate to good yields (55-80%). Conditions for the deracemisation of primary amines using a MAO-N/borane system were further optimised using THN as a template addressing substrate load, nature of the enzyme preparation, buffer systems, borane sources, and organic co-solvents. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.