Research progress in synthesis of Lepadiformine

Lepadiformine, a structurally unique azaspiro-fused tricyclic marine alkaloid, exhibits cytotoxicity against diverse cell lines and demonstrates significant activity against cardiovascular diseases. It has attracted considerable attention in the field of synthetic chemistry. The key challenges include the stereoselective construction of the azacrown carbon stereocenter and the assembly of its intricate tricyclic system. Following its initial isolation, numerous research groups have explored diverse synthetic strategies targeting this molecular architecture. These efforts have yielded multiple synthetic pathways characterized by varying degrees of efficiency and stereochemical control. This review systematically examines the evolution of synthetic approaches to Lepadiformine, with particular emphasis on innovative methodologies for spirocycle formation and asymmetric induction at the pivotal quaternary carbon center.