Discovery, Total Synthesis, and SAR of Anaenamides A and B: Anticancer Cyanobacterial Depsipeptides with a Chlorinated Pharmacophore

Abstract

New modified depsipeptides and geometric isomers, termed anaenamides A (<b>1a</b>) and B (<b>1b</b>), along with the presumptive biosynthetic intermediate, anaenoic acid (<b>2</b>), were discovered from a marine cyanobacterium from Guam. Structures were confirmed by total synthesis. The alkylsalicylic acid fragment and the C-terminal α-chlorinated <i>α,β</i>-unsaturated ester are novelties in cyanobacterial natural products. Cancer cell viability assays indicated that the C-terminal unit serves as the pharmacophore and that the double-bond geometry impacts the cytotoxicity.