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. TITLE=A Concise Synthetic Strategy Towards the Novel Calcium-dependent Lipopeptide Antibiotic, Malacidin A and Analogues JOURNAL=Frontiers in Chemistry VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.687875 DOI=10.3389/fchem.2021.687875 ISSN=2296-2646 ABSTRACT=

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.