School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, M1 7DN Manchester, United Kingdom.
Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceutical, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Bioorg Med Chem. 2018 Apr 1;26(7):1338-1346. doi: 10.1016/j.bmc.2017.07.023. Epub 2017 Jul 13.
A library of 132 racemic chiral amines (α-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.
文库 132 个外消旋手性胺（α-取代甲基苄基胺、二苄基胺、1,2,3,4-四氢萘胺 (THN)、茚满胺、烯丙基和同烯丙基胺、炔丙基胺）对多功能单胺氧化酶 (MAO-N) 变体 D5、D9 和 D11 进行了筛选。MAO-N D9 对大多数底物表现出最高的活性，并应用于一组选定的伯胺的外消旋化。在所有情况下，都实现了出色的对映选择性（ee 值>99%）和中等至良好的产率（55-80%）。使用 MAO-N/硼烷体系对外消旋化伯胺的条件使用 THN 作为模板进一步进行了优化，包括底物负荷、酶制剂的性质、缓冲体系、硼烷源和有机共溶剂。
