Total Synthesis of the Brevicidine and Laterocidine Family of Lipopeptide Antibiotics

Abstract

Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, and a lipidated <i>N</i>-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.