Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases

Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed...

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Autores principales: Winkler, Christoph K, Clay, Dorina, Turrini, Nikolaus G, Lechner, Horst, Kroutil, Wolfgang, Davies, Simon, Debarge, Sebastien, O'Neill, Pat, Steflik, Jeremy, Karmilowicz, Mike, Wong, John W, Faber, Kurt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2014
Materias:
Updates
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498475/
https://www.ncbi.nlm.nih.gov/pubmed/26190962
http://dx.doi.org/10.1002/adsc.201301055
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author Winkler, Christoph K
Clay, Dorina
Turrini, Nikolaus G
Lechner, Horst
Kroutil, Wolfgang
Davies, Simon
Debarge, Sebastien
O'Neill, Pat
Steflik, Jeremy
Karmilowicz, Mike
Wong, John W
Faber, Kurt
author_facet Winkler, Christoph K
Clay, Dorina
Turrini, Nikolaus G
Lechner, Horst
Kroutil, Wolfgang
Davies, Simon
Debarge, Sebastien
O'Neill, Pat
Steflik, Jeremy
Karmilowicz, Mike
Wong, John W
Faber, Kurt
author_sort Winkler, Christoph K
collection PubMed
description Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.
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spelling pubmed-44984752015-07-15 Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases Winkler, Christoph K Clay, Dorina Turrini, Nikolaus G Lechner, Horst Kroutil, Wolfgang Davies, Simon Debarge, Sebastien O'Neill, Pat Steflik, Jeremy Karmilowicz, Mike Wong, John W Faber, Kurt Adv Synth Catal Updates Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester. WILEY-VCH Verlag 2014-05-26 2014-04-09 /pmc/articles/PMC4498475/ /pubmed/26190962 http://dx.doi.org/10.1002/adsc.201301055 Text en © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Updates
Winkler, Christoph K
Clay, Dorina
Turrini, Nikolaus G
Lechner, Horst
Kroutil, Wolfgang
Davies, Simon
Debarge, Sebastien
O'Neill, Pat
Steflik, Jeremy
Karmilowicz, Mike
Wong, John W
Faber, Kurt
Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
title Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
title_full Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
title_fullStr Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
title_full_unstemmed Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
title_short Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
title_sort nitrile as activating group in the asymmetric bioreduction of β-cyanoacrylic acids catalyzed by ene-reductases
topic Updates
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498475/
https://www.ncbi.nlm.nih.gov/pubmed/26190962
http://dx.doi.org/10.1002/adsc.201301055
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