A total synthesis of the antitumour macrolide rhizoxin D

An enantioselective synthesis of rhizoxin D (2), isolated from the plant pathogenic fungus Rhizopus chinensis, is described. The overall strategy is based on elaboration of the δ-lactone-substituted vinyl stannane 7 and the phosphonate-substituted vinyl iodide 9, followed by their coupling to the core 16-membered macrolide 6via 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 8 in an E-selective Horner–Wittig reaction with the macrolide aldehyde 51b.