Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination

N‐Substituted α‐amino esters are widely used as chiral intermediates in a range of pharmaceuticals. Here we report the enantioselective biocatalyic synthesis of N‐substituted α‐amino esters through the direct reductive coupling of α‐ketoesters and amines employing sequence diverse metagenomic imine...

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Autores principales: Yao, Peiyuan, Marshall, James R., Xu, Zefei, Lim, Jesmine, Charnock, Simon J., Zhu, Dunming, Turner, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048798/
https://www.ncbi.nlm.nih.gov/pubmed/33555620
http://dx.doi.org/10.1002/anie.202016589
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author Yao, Peiyuan
Marshall, James R.
Xu, Zefei
Lim, Jesmine
Charnock, Simon J.
Zhu, Dunming
Turner, Nicholas J.
author_facet Yao, Peiyuan
Marshall, James R.
Xu, Zefei
Lim, Jesmine
Charnock, Simon J.
Zhu, Dunming
Turner, Nicholas J.
author_sort Yao, Peiyuan
collection PubMed
description N‐Substituted α‐amino esters are widely used as chiral intermediates in a range of pharmaceuticals. Here we report the enantioselective biocatalyic synthesis of N‐substituted α‐amino esters through the direct reductive coupling of α‐ketoesters and amines employing sequence diverse metagenomic imine reductases (IREDs). Both enantiomers of N‐substituted α‐amino esters were obtained with high conversion and excellent enantioselectivity under mild reaction conditions. In addition >20 different preparative scale transformations were performed highlighting the scalability of this system.
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spelling pubmed-80487982021-04-20 Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination Yao, Peiyuan Marshall, James R. Xu, Zefei Lim, Jesmine Charnock, Simon J. Zhu, Dunming Turner, Nicholas J. Angew Chem Int Ed Engl Communications N‐Substituted α‐amino esters are widely used as chiral intermediates in a range of pharmaceuticals. Here we report the enantioselective biocatalyic synthesis of N‐substituted α‐amino esters through the direct reductive coupling of α‐ketoesters and amines employing sequence diverse metagenomic imine reductases (IREDs). Both enantiomers of N‐substituted α‐amino esters were obtained with high conversion and excellent enantioselectivity under mild reaction conditions. In addition >20 different preparative scale transformations were performed highlighting the scalability of this system. John Wiley and Sons Inc. 2021-03-09 2021-04-12 /pmc/articles/PMC8048798/ /pubmed/33555620 http://dx.doi.org/10.1002/anie.202016589 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Yao, Peiyuan
Marshall, James R.
Xu, Zefei
Lim, Jesmine
Charnock, Simon J.
Zhu, Dunming
Turner, Nicholas J.
Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
title Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
title_full Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
title_fullStr Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
title_full_unstemmed Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
title_short Asymmetric Synthesis of N‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
title_sort asymmetric synthesis of n‐substituted α‐amino esters from α‐ketoesters via imine reductase‐catalyzed reductive amination
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048798/
https://www.ncbi.nlm.nih.gov/pubmed/33555620
http://dx.doi.org/10.1002/anie.202016589
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