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Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

An enzymatic route for phosphorous-carbon- bond formation is developed by discovering new promiscuous activity of lipase. This biocatalytic transformation of phosphorous-carbon- bond addition leads to biologically and pharmacologically relevant α-acyloxy phosphonates with methyl group in α-position....

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Autores principales: Kowalczyk, Paweł, Koszelewski, Dominik, Gawdzik, Barbara, Samsonowicz-Górski, Jan, Kramkowski, Karol, Wypych, Aleksandra, Lizut, Rafał, Ostaszewski, Ryszard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912074/
https://www.ncbi.nlm.nih.gov/pubmed/35269205
http://dx.doi.org/10.3390/ma15051975
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author Kowalczyk, Paweł
Koszelewski, Dominik
Gawdzik, Barbara
Samsonowicz-Górski, Jan
Kramkowski, Karol
Wypych, Aleksandra
Lizut, Rafał
Ostaszewski, Ryszard
author_facet Kowalczyk, Paweł
Koszelewski, Dominik
Gawdzik, Barbara
Samsonowicz-Górski, Jan
Kramkowski, Karol
Wypych, Aleksandra
Lizut, Rafał
Ostaszewski, Ryszard
author_sort Kowalczyk, Paweł
collection PubMed
description An enzymatic route for phosphorous-carbon- bond formation is developed by discovering new promiscuous activity of lipase. This biocatalytic transformation of phosphorous-carbon- bond addition leads to biologically and pharmacologically relevant α-acyloxy phosphonates with methyl group in α-position. A series of target compounds were synthesized with yields ranging from 54% to 83% by enzymatic reaction with Candida cylindracea (CcL) lipase via Markovnikov addition of H-phosphites to vinyl esters. We carefully analyzed the best conditions for the given reaction such as the type of enzyme, temperature, and type of solvent. The developed protocol is applicable to a range of H-phosphites and vinyl esters significantly simplifying the preparation of synthetically challenging α-pivaloyloxy phosphonates. Further, the obtained compounds were validated as new potential antimicrobial drugs with characteristic E. coli bacterial strains and DNA modification recognized by the Fpg protein, N-methyl purine glycosylases as new substrates. The impact of the methyl group located in the α-position of the studied α-acyloxy phosphonates on the antimicrobial activity was demonstrated. The pivotal role of this group on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.
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spelling pubmed-89120742022-03-11 Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives Kowalczyk, Paweł Koszelewski, Dominik Gawdzik, Barbara Samsonowicz-Górski, Jan Kramkowski, Karol Wypych, Aleksandra Lizut, Rafał Ostaszewski, Ryszard Materials (Basel) Article An enzymatic route for phosphorous-carbon- bond formation is developed by discovering new promiscuous activity of lipase. This biocatalytic transformation of phosphorous-carbon- bond addition leads to biologically and pharmacologically relevant α-acyloxy phosphonates with methyl group in α-position. A series of target compounds were synthesized with yields ranging from 54% to 83% by enzymatic reaction with Candida cylindracea (CcL) lipase via Markovnikov addition of H-phosphites to vinyl esters. We carefully analyzed the best conditions for the given reaction such as the type of enzyme, temperature, and type of solvent. The developed protocol is applicable to a range of H-phosphites and vinyl esters significantly simplifying the preparation of synthetically challenging α-pivaloyloxy phosphonates. Further, the obtained compounds were validated as new potential antimicrobial drugs with characteristic E. coli bacterial strains and DNA modification recognized by the Fpg protein, N-methyl purine glycosylases as new substrates. The impact of the methyl group located in the α-position of the studied α-acyloxy phosphonates on the antimicrobial activity was demonstrated. The pivotal role of this group on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. MDPI 2022-03-07 /pmc/articles/PMC8912074/ /pubmed/35269205 http://dx.doi.org/10.3390/ma15051975 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
Kowalczyk, Paweł
Koszelewski, Dominik
Gawdzik, Barbara
Samsonowicz-Górski, Jan
Kramkowski, Karol
Wypych, Aleksandra
Lizut, Rafał
Ostaszewski, Ryszard
Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
title Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
title_full Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
title_fullStr Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
title_full_unstemmed Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
title_short Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
title_sort promiscuous lipase-catalyzed markovnikov addition of h-phosphites to vinyl esters for the synthesis of cytotoxic α-acyloxy phosphonate derivatives
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912074/
https://www.ncbi.nlm.nih.gov/pubmed/35269205
http://dx.doi.org/10.3390/ma15051975
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