AbstractA 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.