Organic Chemistry Seminar

Abstract: Concise and scalable syntheses of complex bioactive molecules provide the foundation for studying structural-activity relationships, preparing analogs, and advancing therapeutical potential. To address this challenge, we have developed a versatile platform strategy centered on polyfunctional intermediates equipped with orthogonally reactive groups. This approach facilitates streamlined C–C bond formations with minimal protecting group and functional group manipulations, enabling concise and scalable routes to polycyclic natural products of diverse biosynthetic origins. Applying this method, we achieved concise syntheses of marine (nor)diterpenoid scabrolide A and havellockate, as well as the triterpenoid glycinoeclepin A—a picomolar soybean cyst nematode hatching factor. Furthermore, we have expanded this strategy through a chemoenzymatic approach, repurposing simple substituted benzene as a non-canonical triene-type polyfunctional intermediate. This enabled a 16-step, scalable and stereoselective synthesis of tetrodotoxin, a celebrated natural alkaloid with nanomolar sodium channel blocking properties.