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Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers

The syntheses of (+)-16-epi- and (+)-11,15-di-epi-danicalipin A (2 and 3) are reported. The conformations of the parent diols 5 and 6 as well as the corresponding disulfates 2 and 3 were determined on the basis of J-based configuration analysis and supported by calculations. The impact of configurat...

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Autores principales: Boshkow, J., Fischer, S., Bailey, A. M., Wolfrum, S., Carreira, E. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632803/
https://www.ncbi.nlm.nih.gov/pubmed/29147515
http://dx.doi.org/10.1039/c7sc03124f
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author Boshkow, J.
Fischer, S.
Bailey, A. M.
Wolfrum, S.
Carreira, E. M.
author_facet Boshkow, J.
Fischer, S.
Bailey, A. M.
Wolfrum, S.
Carreira, E. M.
author_sort Boshkow, J.
collection PubMed
description The syntheses of (+)-16-epi- and (+)-11,15-di-epi-danicalipin A (2 and 3) are reported. The conformations of the parent diols 5 and 6 as well as the corresponding disulfates 2 and 3 were determined on the basis of J-based configuration analysis and supported by calculations. The impact of configuration on membrane permeability in Gram-negative bacteria and mammalian cell lines was assessed as well as cytotoxicity. Although diastereomer 2 showed similar behavior to natural (+)-danicalipin A (1), strikingly, the more flexible C11,C15-epimer 3 had no effect on permeability and proved equally or more toxic towards multiple cell lines.
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spelling pubmed-56328032017-11-16 Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers Boshkow, J. Fischer, S. Bailey, A. M. Wolfrum, S. Carreira, E. M. Chem Sci Chemistry The syntheses of (+)-16-epi- and (+)-11,15-di-epi-danicalipin A (2 and 3) are reported. The conformations of the parent diols 5 and 6 as well as the corresponding disulfates 2 and 3 were determined on the basis of J-based configuration analysis and supported by calculations. The impact of configuration on membrane permeability in Gram-negative bacteria and mammalian cell lines was assessed as well as cytotoxicity. Although diastereomer 2 showed similar behavior to natural (+)-danicalipin A (1), strikingly, the more flexible C11,C15-epimer 3 had no effect on permeability and proved equally or more toxic towards multiple cell lines. Royal Society of Chemistry 2017-10-01 2017-08-09 /pmc/articles/PMC5632803/ /pubmed/29147515 http://dx.doi.org/10.1039/c7sc03124f Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0)
spellingShingle Chemistry
Boshkow, J.
Fischer, S.
Bailey, A. M.
Wolfrum, S.
Carreira, E. M.
Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers
title Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers
title_full Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers
title_fullStr Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers
title_full_unstemmed Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers
title_short Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers
title_sort stereochemistry and biological activity of chlorinated lipids: a study of danicalipin a and selected diastereomers
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632803/
https://www.ncbi.nlm.nih.gov/pubmed/29147515
http://dx.doi.org/10.1039/c7sc03124f
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