Issue 12, 2022

Synthetic studies with the brevicidine and laterocidine lipopeptide antibiotics including analogues with enhanced properties and in vivo efficacy

Abstract

Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, and a lipidated N-terminus, these lipopeptides exhibit potent and selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine and laterocidine accessible by fermentation of the producing microorganisms, synthetic routes to these lipopeptides present an attractive alternative. We here report the convenient solid-phase syntheses of both brevicidine and laterocidine and confirm their potent anti-Gram-negative activities. The synthetic routes developed also provide convenient access to novel structural analogues of both brevicidine and laterocidine that display improved hydrolytic stability while maintaining potent antibacterial activity in both in vitro assays and in vivo infection models.

Graphical abstract: Synthetic studies with the brevicidine and laterocidine lipopeptide antibiotics including analogues with enhanced properties and in vivo efficacy

Supplementary files

Article information

Article type
Edge Article
Submitted
07 Jan 2022
Accepted
09 Feb 2022
First published
23 Feb 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 3563-3570

Synthetic studies with the brevicidine and laterocidine lipopeptide antibiotics including analogues with enhanced properties and in vivo efficacy

K. Al Ayed, R. D. Ballantine, M. Hoekstra, S. J. Bann, C. M. J. Wesseling, A. T. Bakker, Z. Zhong, Y. Li, N. C. Brüchle, M. van der Stelt, S. A. Cochrane and N. I. Martin, Chem. Sci., 2022, 13, 3563 DOI: 10.1039/D2SC00143H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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