Protecting-group directed stereoselective intramolecular Nozaki-Hiyama-Kishi reaction: a concise and efficient total synthesis of amphidinolactone A

A convergent total synthesis of amphidinolactone A, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., is described in 13 linear steps. The key step in the synthetic sequence involves an intramolecular Nozaki-Hiyama-Kishi (NHK) reaction for the construction of the 13-membered lactone ring by union of two fragments derived from a single chiral epoxide. The stereochemical outcome of the NHK reaction has been supported by computational studies