Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

Fei-fei Chen; Sebastian C. Cosgrove; William R. Birmingham; Juan Mangas-sanchez; Joan Citoler; Matthew P. Thompson; Gao-wei Zheng; Jian-he Xu; Nicholas J. Turner

doi:10.1021/acscatal.9b03889

Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

Fei-fei Chen, Sebastian C. Cosgrove, William R. Birmingham, Juan Mangas-sanchez, Joan Citoler, Matthew P. Thompson, Gao-wei Zheng, Jian-he Xu, Nicholas J. Turner

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Abstract

Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.

Original language	English
Pages (from-to)	11813-11818
Journal	ACS Catalysis
Volume	9
Issue number	12
Early online date	18 Nov 2019
DOIs	https://doi.org/10.1021/acscatal.9b03889
Publication status	Published - 6 Dec 2019

Keywords

amine dehydrogenase
biocatalysis
chiral amino alcohols
directed evolution
reductive amination

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10.1021/acscatal.9b03889

ChenetalRevisedManuscriptAccepted author manuscript, 1.76 MB

https://pubs.acs.org/doi/10.1021/acscatal.9b03889

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title = "Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases",

abstract = "Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.",

keywords = "amine dehydrogenase, biocatalysis, chiral amino alcohols, directed evolution, reductive amination",

author = "Fei-fei Chen and Cosgrove, {Sebastian C.} and Birmingham, {William R.} and Juan Mangas-sanchez and Joan Citoler and Thompson, {Matthew P.} and Gao-wei Zheng and Jian-he Xu and Turner, {Nicholas J.}",

year = "2019",

month = dec,

day = "6",

doi = "10.1021/acscatal.9b03889",

language = "English",

volume = "9",

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journal = "ACS Catalysis",

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T1 - Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

AU - Chen, Fei-fei

AU - Cosgrove, Sebastian C.

AU - Birmingham, William R.

AU - Mangas-sanchez, Juan

AU - Citoler, Joan

AU - Thompson, Matthew P.

AU - Zheng, Gao-wei

AU - Xu, Jian-he

AU - Turner, Nicholas J.

PY - 2019/12/6

Y1 - 2019/12/6

N2 - Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.

AB - Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.

KW - amine dehydrogenase

KW - biocatalysis

KW - chiral amino alcohols

KW - directed evolution

KW - reductive amination

U2 - 10.1021/acscatal.9b03889

DO - 10.1021/acscatal.9b03889

M3 - Article

SN - 2155-5435

VL - 9

SP - 11813

EP - 11818

JO - ACS Catalysis

JF - ACS Catalysis

IS - 12

ER -

Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

Abstract

Keywords

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