Isolation and First Total Synthesis of PM100618 and PM110049, Two Structurally Distinct Marine-Derived Anticancer...

We report the discovery, structural elucidation, and first total synthesis of two unprecedented marine oxazole derivatives, PM100618 and PM110049, isolated from the Papua New Guinean sponge Rhabdastrella rowi. Both compounds exhibit potent in vitro cytotoxic activity at nanomolar concentrations. A highly convergent and efficient total synthesis of PM100618 and PM110049 was achieved in 22 and 21 steps, respectively (longest linear sequence: 15 steps) through the coupling of two complex fragments. This synthetic route provides ready access to these scarce natural products, enabling advanced pharmacological evaluation and mechanistic studies of this new class of marine-derived anticancer agents.