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Bioorg Med Chem. 2018 Apr 1;26(7):1338-1346. doi: 10.1016/j.bmc.2017.07.023. Epub 2017 Jul 13.

Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines.

Author information

1
School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, M1 7DN Manchester, United Kingdom.
2
Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceutical, Turnhoutseweg 30, B-2340 Beerse, Belgium.
3
Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceutical, Turnhoutseweg 30, B-2340 Beerse, Belgium. Electronic address: swagscha@its.jnj.com.
4
School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, M1 7DN Manchester, United Kingdom. Electronic address: nicholas.turner@manchester.ac.uk.

Abstract

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.

KEYWORDS:

Borane; Chirality; Deracemisation; Enantiomerically pure chiral amines; Enzyme catalysis; Monoamine oxidase (MAO-N)

PMID:
28764963
DOI:
10.1016/j.bmc.2017.07.023
[Indexed for MEDLINE]

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