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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7663146 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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