Synthetic Studies with the Brevicidine and Laterocidine Lipopeptide Antibiotics Including Analogues with Enhanced Properties and in vivo Efficacy

10 January 2022, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


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 assay and in vivo infection models.


Cyclic peptides
Total synthesis

Supplementary materials

Preprint supporting information
Supporting information including synthetic details, analytical data, and a description of the in vitro and in vivo assays used.


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