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A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues

Malacidin A is a novel calcium-dependent lipopeptide antibiotic with excellent activity against Gram-positive pathogens. Herein, a concise and robust synthetic route toward malacidin A is reported, employing 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis of a linear precursor, including la...

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Autores principales: Kovalenko, Nadiia, Howard, Georgina K., Swain, Jonathan A., Hermant, Yann, Cameron, Alan J., Cook, Gregory M., Ferguson, Scott A., Stubbing, Louise A., Harris, Paul W. R., Brimble, Margaret A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372822/
https://www.ncbi.nlm.nih.gov/pubmed/34422759
http://dx.doi.org/10.3389/fchem.2021.687875
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author Kovalenko, Nadiia
Howard, Georgina K.
Swain, Jonathan A.
Hermant, Yann
Cameron, Alan J.
Cook, Gregory M.
Ferguson, Scott A.
Stubbing, Louise A.
Harris, Paul W. R.
Brimble, Margaret A.
author_facet Kovalenko, Nadiia
Howard, Georgina K.
Swain, Jonathan A.
Hermant, Yann
Cameron, Alan J.
Cook, Gregory M.
Ferguson, Scott A.
Stubbing, Louise A.
Harris, Paul W. R.
Brimble, Margaret A.
author_sort Kovalenko, Nadiia
collection PubMed
description Malacidin A is a novel calcium-dependent lipopeptide antibiotic with excellent activity against Gram-positive pathogens. Herein, a concise and robust synthetic route toward malacidin A is reported, employing 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis of a linear precursor, including late-stage incorporation of the lipid tail, followed by solution-phase cyclization. The versatility of this synthetic strategy was further demonstrated by synthesis of a diastereomeric variant of malacidin A and a small library of simplified analogues with variation of the lipid moiety.
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spelling pubmed-83728222021-08-19 A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues Kovalenko, Nadiia Howard, Georgina K. Swain, Jonathan A. Hermant, Yann Cameron, Alan J. Cook, Gregory M. Ferguson, Scott A. Stubbing, Louise A. Harris, Paul W. R. Brimble, Margaret A. Front Chem Chemistry Malacidin A is a novel calcium-dependent lipopeptide antibiotic with excellent activity against Gram-positive pathogens. Herein, a concise and robust synthetic route toward malacidin A is reported, employing 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis of a linear precursor, including late-stage incorporation of the lipid tail, followed by solution-phase cyclization. The versatility of this synthetic strategy was further demonstrated by synthesis of a diastereomeric variant of malacidin A and a small library of simplified analogues with variation of the lipid moiety. Frontiers Media S.A. 2021-08-04 /pmc/articles/PMC8372822/ /pubmed/34422759 http://dx.doi.org/10.3389/fchem.2021.687875 Text en Copyright © 2021 Kovalenko, Howard, Swain, Hermant, Cameron, Cook, Ferguson, Stubbing, Harris and Brimble. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Kovalenko, Nadiia
Howard, Georgina K.
Swain, Jonathan A.
Hermant, Yann
Cameron, Alan J.
Cook, Gregory M.
Ferguson, Scott A.
Stubbing, Louise A.
Harris, Paul W. R.
Brimble, Margaret A.
A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues
title A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues
title_full A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues
title_fullStr A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues
title_full_unstemmed A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues
title_short A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues
title_sort concise synthetic strategy towards the novel calcium-dependent lipopeptide antibiotic, malacidin a and analogues
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372822/
https://www.ncbi.nlm.nih.gov/pubmed/34422759
http://dx.doi.org/10.3389/fchem.2021.687875
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