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

Susanne Herter; Florian Medina; Simon Wagschal; Cyril Benhaïm; Friedemann Leipold; Nicholas J. Turner

doi:10.1016/j.bmc.2017.07.023

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

Susanne Herter, Florian Medina, Simon Wagschal^*, Cyril Benhaïm, Friedemann Leipold, Nicholas J. Turner

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Journal	Bioorganic and Medicinal Chemistry
Early online date	13 Jul 2017
DOIs	https://doi.org/10.1016/j.bmc.2017.07.023
Publication status	Published - 2017

Keywords

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

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10.1016/j.bmc.2017.07.023

Herter et al MS Bioorg Med Chem AAMAccepted author manuscript, 1.58 MB

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

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)",

author = "Susanne Herter and Florian Medina and Simon Wagschal and Cyril Benha{\"i}m and Friedemann Leipold and Turner, {Nicholas J.}",

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language = "English",

journal = "Bioorganic and Medicinal Chemistry",

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AU - Herter, Susanne

AU - Medina, Florian

AU - Wagschal, Simon

AU - Benhaïm, Cyril

AU - Leipold, Friedemann

AU - Turner, Nicholas J.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Borane

KW - Chirality

KW - Deracemisation

KW - Enantiomerically pure chiral amines

KW - Enzyme catalysis

KW - Monoamine oxidase (MAO-N)

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DO - 10.1016/j.bmc.2017.07.023

M3 - Article

AN - SCOPUS:85026453541

SN - 0968-0896

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

ER -

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

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Keywords

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