Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines

Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with...

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Autores principales: Lakó, Ágnes, Molnár, Zsófia, Mendonça, Ricardo, Poppe, László
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057730/
https://www.ncbi.nlm.nih.gov/pubmed/35519186
http://dx.doi.org/10.1039/d0ra08134e
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author Lakó, Ágnes
Molnár, Zsófia
Mendonça, Ricardo
Poppe, László
author_facet Lakó, Ágnes
Molnár, Zsófia
Mendonça, Ricardo
Poppe, László
author_sort Lakó, Ágnes
collection PubMed
description Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88–89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee.
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spelling pubmed-90577302022-05-04 Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines Lakó, Ágnes Molnár, Zsófia Mendonça, Ricardo Poppe, László RSC Adv Chemistry Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88–89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee. The Royal Society of Chemistry 2020-11-10 /pmc/articles/PMC9057730/ /pubmed/35519186 http://dx.doi.org/10.1039/d0ra08134e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Lakó, Ágnes
Molnár, Zsófia
Mendonça, Ricardo
Poppe, László
Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
title Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
title_full Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
title_fullStr Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
title_full_unstemmed Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
title_short Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
title_sort transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057730/
https://www.ncbi.nlm.nih.gov/pubmed/35519186
http://dx.doi.org/10.1039/d0ra08134e
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AT mendoncaricardo transaminasemediatedsynthesisofenantiopuredruglike134disubstitutedphenylpropan2amines
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