A Concise Ring-Expansion Route to the Compact Core of Platensimycin†

Recently, researchers at Merck disclosed a new natural product, platensimycin (1; Figure 1),[1] which was obtained by screening a large collection of South African soil samples using a novel antibiotic assay approach. Characterization revealed a unique compact core connected to a highly oxygenated and unusual aromatic ring through a propionate tether. Platensimycin has a novel mechanism of action, inhibiting the β-ketoacyl-(acyl carrier protein) synthase (FabF) in the bacterial fatty acid synthetic pathway.[2] Several new members of this class have since been reported.[3] These differ only in functionalization of the carboxylate terminus. This attractive natural product target has also encouraged researchers to engineer strains to improve its production.[4]