Total Synthesis of Euphopia B and Discovery of a Selective Inhibitor of Potassium Efflux-Independent NLRP3 Inflammasome Activation

Herein, we report the first asymmetric total synthesis of the structurally distinctive jatrophane diterpenoid euphopia B, which contains ten contiguous stereocenters and multiple oxygenated functional groups. A robust and scalable synthetic route was developed featuring copper-catalyzed asymmetric hydroboration, Claisen rearrangement, and SmI₂-mediated cyclization as key steps. This synthesis enables single-batch preparation of euphopia B on a > 100 mg scale and provides a solid foundation for biological studies. Systematic bioactivity screening subsequently revealed that euphopia B selectively inhibits NLRP3 inflammasome activation induced by potassium efflux-independent activators, thereby providing a critical chemical probe for elucidating the complex activation mechanism of NLRP3.