Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases

[Image: see text] The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through siz...

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Autores principales: Winkler, Christoph K., Clay, Dorina, Davies, Simon, O’Neill, Pat, McDaid, Paul, Debarge, Sebastien, Steflik, Jeremy, Karmilowicz, Mike, Wong, John W., Faber, Kurt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2013
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579311/
https://www.ncbi.nlm.nih.gov/pubmed/23316696
http://dx.doi.org/10.1021/jo302484p
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author Winkler, Christoph K.
Clay, Dorina
Davies, Simon
O’Neill, Pat
McDaid, Paul
Debarge, Sebastien
Steflik, Jeremy
Karmilowicz, Mike
Wong, John W.
Faber, Kurt
author_facet Winkler, Christoph K.
Clay, Dorina
Davies, Simon
O’Neill, Pat
McDaid, Paul
Debarge, Sebastien
Steflik, Jeremy
Karmilowicz, Mike
Wong, John W.
Faber, Kurt
author_sort Winkler, Christoph K.
collection PubMed
description [Image: see text] The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.
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spelling pubmed-35793112013-02-25 Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases Winkler, Christoph K. Clay, Dorina Davies, Simon O’Neill, Pat McDaid, Paul Debarge, Sebastien Steflik, Jeremy Karmilowicz, Mike Wong, John W. Faber, Kurt J Org Chem [Image: see text] The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications. American Chemical Society 2013-01-14 2013-02-15 /pmc/articles/PMC3579311/ /pubmed/23316696 http://dx.doi.org/10.1021/jo302484p Text en Copyright © 2013 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Winkler, Christoph K.
Clay, Dorina
Davies, Simon
O’Neill, Pat
McDaid, Paul
Debarge, Sebastien
Steflik, Jeremy
Karmilowicz, Mike
Wong, John W.
Faber, Kurt
Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
title Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
title_full Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
title_fullStr Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
title_full_unstemmed Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
title_short Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
title_sort chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of β-cyanoacrylate esters using ene-reductases
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579311/
https://www.ncbi.nlm.nih.gov/pubmed/23316696
http://dx.doi.org/10.1021/jo302484p
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