Chemoselective annulation of a tropolone linchpin enables divergent total syntheses of algicidal roseobacticides.

Abstract

Roseobacticides are algicidal tropofuranones produced by the marine roseobacter Phaeobacter inhibens during interactions with the bloom-forming coccolithophore Gephyrocapsa huxleyi. We report a divergent synthesis based on chemoselective annulation of the multifunctional 2-methoxy-6-(methylthio)tropone with aryl- and indolylacetates, followed by subsequent oxidation or substitution at the C-7 sulfur functionality, enabling the first total syntheses of roseobacticides A, B, C and I and the proposed structure of L. Synthetic roseobacticides showed potent algicidal activity against G. huxleyi and Amphidinium carterae.