Configuration and Conformation of the 8,9-Diol-Amphidinolide B Scaffold

Marine dinoflagellates of the genus Amphidinium are a unique bioresource for the production of cytotoxic macrolides, such as amphidinolides. Due to mass-material unavailability, the relative and absolute configuration determination of these macrolides has long been a challenge. Based on our modern microalgal pilot-scale cultivation platform, two 8,9-diol analogs of amphidinolide B, named amphidinolides B10 (1) and B11 (2), were obtained from microalgal cells of the marine dinoflagellate Amphidinium gibbosum. The configuration assignment of these macrolides was achieved by J-based configurational analysis (JBCA) and single-crystal X-ray diffraction (Ga Kα) analysis. By comparing the three-dimensional structure of amphidinolide B1, H2, and B10 (1), it was concluded that the rigidly allylic 8,9-epoxy ring-opening might trigger a conformational switch, resulting in the collapse of the extended 26-membered macrocyclic framework of amphidinolide B into the deep-folding conformation of the 8,9-diol-amphidinolide B scaffold, associated with selective cytotoxicity against cancer cell lines.