Frontiers in Chemistry (Aug 2021)

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

  • Nadiia Kovalenko,
  • Georgina K. Howard,
  • Jonathan A. Swain,
  • Yann Hermant,
  • Alan J. Cameron,
  • Alan J. Cameron,
  • Alan J. Cameron,
  • Gregory M. Cook,
  • Gregory M. Cook,
  • Scott A. Ferguson,
  • Louise A. Stubbing,
  • Paul W. R. Harris,
  • Paul W. R. Harris,
  • Paul W. R. Harris,
  • Margaret A. Brimble,
  • Margaret A. Brimble,
  • Margaret A. Brimble

DOI
https://doi.org/10.3389/fchem.2021.687875
Journal volume & issue
Vol. 9

Abstract

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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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