Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase

Godwin A. Aleku; Juan Mangas-Sanchez; Joan Citoler; Scott P. France; Sarah L. Montgomery; Rachel S. Heath; Matthew P. Thompson; Nicholas J. Turner

doi:10.1002/cctc.201701484

Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase

Godwin A. Aleku, Juan Mangas-Sanchez, Joan Citoler, Scott P. France, Sarah L. Montgomery, Rachel S. Heath, Matthew P. Thompson, Nicholas J. Turner^*

^*Corresponding author for this work

The University of Manchester

UMIST

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

64 Downloads (Pure)

Abstract

The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99 %. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98 % and >99 % ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.

Original language	English
Pages (from-to)	515-519
Number of pages	5
Journal	ChemCatChem
Volume	10
Issue number	3
Early online date	15 Sept 2017
DOIs	https://doi.org/10.1002/cctc.201701484
Publication status	Published - 7 Feb 2018

Keywords

amines
biocatalysis
chirality
deracemization
kinetic resolution

Research Beacons, Institutes and Platforms

Manchester Institute of Biotechnology

Access to Document

10.1002/cctc.201701484

Aleku_Kinetic resolution_AcceptedArticle-1Accepted author manuscript, 885 KB

Cite this

@article{725bcee4544c4cf197c2d74bd9199939,

title = "Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase",

abstract = "The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99 %. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98 % and >99 % ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.",

keywords = "amines, biocatalysis, chirality, deracemization, kinetic resolution",

author = "Aleku, {Godwin A.} and Juan Mangas-Sanchez and Joan Citoler and France, {Scott P.} and Montgomery, {Sarah L.} and Heath, {Rachel S.} and Thompson, {Matthew P.} and Turner, {Nicholas J.}",

year = "2018",

month = feb,

day = "7",

doi = "10.1002/cctc.201701484",

language = "English",

volume = "10",

pages = "515--519",

journal = "ChemCatChem",

issn = "1867-3880",

publisher = "John Wiley & Sons Ltd",

number = "3",

}

TY - JOUR

T1 - Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase

AU - Aleku, Godwin A.

AU - Mangas-Sanchez, Juan

AU - Citoler, Joan

AU - France, Scott P.

AU - Montgomery, Sarah L.

AU - Heath, Rachel S.

AU - Thompson, Matthew P.

AU - Turner, Nicholas J.

PY - 2018/2/7

Y1 - 2018/2/7

N2 - The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99 %. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98 % and >99 % ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.

AB - The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99 %. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98 % and >99 % ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.

KW - amines

KW - biocatalysis

KW - chirality

KW - deracemization

KW - kinetic resolution

U2 - 10.1002/cctc.201701484

DO - 10.1002/cctc.201701484

M3 - Article

AN - SCOPUS:85041802937

SN - 1867-3880

VL - 10

SP - 515

EP - 519

JO - ChemCatChem

JF - ChemCatChem

IS - 3

ER -

Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase

Abstract

Keywords

Research Beacons, Institutes and Platforms

Access to Document

Fingerprint

Cite this