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Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation

The synthesis of glycosyl-β-1C-(phosphino)-phosphonates is a challenge since it has not yet been described. In this paper, we report an innovative synthetic method for their preparation from Glc-, Man-, and GlcNAc- lactone derivatives. The proposed original strategy involves the addition of the corr...

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Autores principales: Bosco, Michaël, Paik, Su-Jin, Busca, Patricia, Moore, Stuart E. H., Gravier-Pelletier, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663146/
https://www.ncbi.nlm.nih.gov/pubmed/33121078
http://dx.doi.org/10.3390/molecules25214969
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author Bosco, Michaël
Paik, Su-Jin
Busca, Patricia
Moore, Stuart E. H.
Gravier-Pelletier, Christine
author_facet Bosco, Michaël
Paik, Su-Jin
Busca, Patricia
Moore, Stuart E. H.
Gravier-Pelletier, Christine
author_sort Bosco, Michaël
collection PubMed
description The synthesis of glycosyl-β-1C-(phosphino)-phosphonates is a challenge since it has not yet been described. In this paper, we report an innovative synthetic method for their preparation from Glc-, Man-, and GlcNAc- lactone derivatives. The proposed original strategy involves the addition of the corresponding δ-hexonolactones onto the dianion of (methylphosphino) phosphonate as a key step, followed by dehydration and stereoselective addition of dihydrogen on the resulting double bond. Final deprotection provides the new glycosyl diphosphate analogs in 35%, 36%, and 10% yield over 6 steps from the corresponding δ-hexonolactones. The synthetized compounds were evaluated as inhibitors of phosphatase and diphosphatase activities and found to have complex concentration-dependent activatory and inhibitory properties on alkaline phosphatase. The synthetized tools should be useful to study other enzymes such as transferases.
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spelling pubmed-76631462020-11-14 Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation Bosco, Michaël Paik, Su-Jin Busca, Patricia Moore, Stuart E. H. Gravier-Pelletier, Christine Molecules Article The synthesis of glycosyl-β-1C-(phosphino)-phosphonates is a challenge since it has not yet been described. In this paper, we report an innovative synthetic method for their preparation from Glc-, Man-, and GlcNAc- lactone derivatives. The proposed original strategy involves the addition of the corresponding δ-hexonolactones onto the dianion of (methylphosphino) phosphonate as a key step, followed by dehydration and stereoselective addition of dihydrogen on the resulting double bond. Final deprotection provides the new glycosyl diphosphate analogs in 35%, 36%, and 10% yield over 6 steps from the corresponding δ-hexonolactones. The synthetized compounds were evaluated as inhibitors of phosphatase and diphosphatase activities and found to have complex concentration-dependent activatory and inhibitory properties on alkaline phosphatase. The synthetized tools should be useful to study other enzymes such as transferases. MDPI 2020-10-27 /pmc/articles/PMC7663146/ /pubmed/33121078 http://dx.doi.org/10.3390/molecules25214969 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bosco, Michaël
Paik, Su-Jin
Busca, Patricia
Moore, Stuart E. H.
Gravier-Pelletier, Christine
Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation
title Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation
title_full Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation
title_fullStr Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation
title_full_unstemmed Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation
title_short Synthetic Route to Glycosyl β-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation
title_sort synthetic route to glycosyl β-1c-(phosphino)-phosphonates as unprecedented stable glycosyl diphosphate analogs and their preliminary biological evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663146/
https://www.ncbi.nlm.nih.gov/pubmed/33121078
http://dx.doi.org/10.3390/molecules25214969
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