Total Synthesis Of Polycyclic Xanthone Natural Product Kibdelone C

Polycyclic xanthone natural products（PXNPs）are a family of polyketides with complex structure,excellent bioactivity and great potential for medicine.Notably,kibdelone C displays significant activities against a range of human tumors by the NCI60-cell panel assays(GI₅₀<1 nm).However,due to the limited amount of material from natural source and fewer synthesis route,the research of pharmacology and biological activity of related compounds are restricted.To solve these problems,we started to synthesis kibdelone C,which could lead to modular synthesis of these molecules,and lay the foundation for the research of related pharmaceutical chemistry.We envisioned that BCD ring is the core structure of this kind of natural products,which could derive to A ring and EF ring respectively,and the modular synthesis of this family of compound could be realized.Our synthesis commenced with the preparation of the core BCD ring system.We studied the photo-induced 6πelectric cyclization and synthesis 4 compounds containing BCD rings in large-scale.A ring was constructed via an InBr₃-promoted lactonization after screening the reaction of photo-induced 6πelectric,acid-promoted and base-promoted cyclization.We synthesized 3 compounds containing ABCD rings by InBr₃-promoted lactonization.To constract EF ring system,a key DMAP-mediated oxa-Michael/aldol cascade reaction was utilized to install the tetrahydroxanthone fragment after screening the reaction of[3+2]cycloaddition,acid-promoted Prins reaction and base-mediated oxa-Michael/aldol cascade reaction.Finally,formal synthesis of kibdelone C was achieved through the known approach.