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Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate

Chiral amines and alcohols are synthons of numerous pharmaceutically-relevant compounds. The previously developed enzymatic kinetic resolution approaches utilize a chiral racemic molecule and achiral acyl donor (or acyl acceptor). Thus, only one enantiodivergent step of the catalytic cycle is engage...

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Autores principales: Samsonowicz-Górski, Jan, Brodzka, Anna, Ostaszewski, Ryszard, Koszelewski, Dominik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319036/
https://www.ncbi.nlm.nih.gov/pubmed/35889218
http://dx.doi.org/10.3390/molecules27144346
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author Samsonowicz-Górski, Jan
Brodzka, Anna
Ostaszewski, Ryszard
Koszelewski, Dominik
author_facet Samsonowicz-Górski, Jan
Brodzka, Anna
Ostaszewski, Ryszard
Koszelewski, Dominik
author_sort Samsonowicz-Górski, Jan
collection PubMed
description Chiral amines and alcohols are synthons of numerous pharmaceutically-relevant compounds. The previously developed enzymatic kinetic resolution approaches utilize a chiral racemic molecule and achiral acyl donor (or acyl acceptor). Thus, only one enantiodivergent step of the catalytic cycle is engaged, which does not fully exploit the enzyme’s abilities. The first carbonate-mediated example of simultaneous double chemoselective kinetic resolution of chiral amines and alcohols is described. Herein, we established a biocatalytic approach towards four optically-pure compounds (>99% ee, Enantioselectivity: E > 200) via double enzymatic kinetic resolution, engaging chiral organic carbonates as acyl donors. High enantioselectivity was ensured by extraordinary chemoselectivity in lipase-catalyzed formation of unsymmetrical organic carbonates and engaged in a process applicable for the synthesis of enantiopure organic precursors of valuable compounds. This study focused not only on preparative synthesis, but additionally the catalytic mechanism was discussed and the clear impact of this rarely observed carbonate-derived acyl enzyme was shown. The presented protocol is characterized by atom efficiency, acyl donor sustainability, easy acyl group removal, mild reaction conditions, and biocatalyst recyclability, which significantly decreases the cost of the reported process.
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spelling pubmed-93190362022-07-27 Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate Samsonowicz-Górski, Jan Brodzka, Anna Ostaszewski, Ryszard Koszelewski, Dominik Molecules Article Chiral amines and alcohols are synthons of numerous pharmaceutically-relevant compounds. The previously developed enzymatic kinetic resolution approaches utilize a chiral racemic molecule and achiral acyl donor (or acyl acceptor). Thus, only one enantiodivergent step of the catalytic cycle is engaged, which does not fully exploit the enzyme’s abilities. The first carbonate-mediated example of simultaneous double chemoselective kinetic resolution of chiral amines and alcohols is described. Herein, we established a biocatalytic approach towards four optically-pure compounds (>99% ee, Enantioselectivity: E > 200) via double enzymatic kinetic resolution, engaging chiral organic carbonates as acyl donors. High enantioselectivity was ensured by extraordinary chemoselectivity in lipase-catalyzed formation of unsymmetrical organic carbonates and engaged in a process applicable for the synthesis of enantiopure organic precursors of valuable compounds. This study focused not only on preparative synthesis, but additionally the catalytic mechanism was discussed and the clear impact of this rarely observed carbonate-derived acyl enzyme was shown. The presented protocol is characterized by atom efficiency, acyl donor sustainability, easy acyl group removal, mild reaction conditions, and biocatalyst recyclability, which significantly decreases the cost of the reported process. MDPI 2022-07-06 /pmc/articles/PMC9319036/ /pubmed/35889218 http://dx.doi.org/10.3390/molecules27144346 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Samsonowicz-Górski, Jan
Brodzka, Anna
Ostaszewski, Ryszard
Koszelewski, Dominik
Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate
title Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate
title_full Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate
title_fullStr Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate
title_full_unstemmed Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate
title_short Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate
title_sort intensification of double kinetic resolution of chiral amines and alcohols via chemoselective formation of a carbonate–enzyme intermediate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319036/
https://www.ncbi.nlm.nih.gov/pubmed/35889218
http://dx.doi.org/10.3390/molecules27144346
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