A total synthesis of the antitumour macrolide rhizoxin D

An enantioselective synthesis of rhizoxin D, isolated from the plant pathogenic fungus Rhizopus chinensis, is described. The overall strategy is based on elaboration of the delta-lactone-substituted vinyl stannane and the phosphonate-substituted vinyl iodide, followed by their coupling to the core 16-membered macrolide via a sequential intermolecular Horner-Wadsworth-Emmons olefination, leading to (50), and by an intramolecular Stille reaction. The triene oxazole-containing side chain in rhizoxin D is then introduced using the phosphine oxide in an E-selective Horner-Wittig reaction with the macrolide aldehyde.