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

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.

SUBMITTER: Kovalenko N

PROVIDER: S-EPMC8372822 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Kovalenko Nadiia N Howard Georgina K GK Swain Jonathan A JA Hermant Yann Y Cameron Alan J AJ Cook Gregory M GM Ferguson Scott A SA Stubbing Louise A LA Harris Paul W R PWR Brimble Margaret A MA

Frontiers in chemistry 20210804

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 malaci ...[more]

PMID: 34422759

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