Cargando…
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....
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
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 |
_version_ | 1784667013554110464 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8912074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kowalczykpaweł promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT koszelewskidominik promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT gawdzikbarbara promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT samsonowiczgorskijan promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT kramkowskikarol promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT wypychaleksandra promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT lizutrafał promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives AT ostaszewskiryszard promiscuouslipasecatalyzedmarkovnikovadditionofhphosphitestovinylestersforthesynthesisofcytotoxicaacyloxyphosphonatederivatives |