Concise synthesis of hemigossypol via sequential palladium-catalyzed regiospecific oxygenations of the naphthalene ring

A total synthetic approach to hemigossypol is described, featuring successive ligand-directed proximal C-H oxygenations and completion of the synthesis in 10 steps with 9.5% total yield. Adjusting the order of the sequence in the installation of the hydroxyl and isopropyl groups for the construction of a 2,3,4,8-tetrasubstituted naphthalene ring, our strategy based on direct functionalization of a naphthalene ring shortens the route and improves the synthesis efficiency, compared with conventional approaches using aromatization of substituted benzene. This regiospecific approach holds promise for achieving rapid access to diverse derivatives of gossypol for biological studies.

Automated summary

This article presents a total synthesis of hemigossypol through ligand-directed C-H oxygenations and completing the synthesis in 10 steps with a total yield of 9.5%. By adjusting the order of hydroxyl and isopropyl group installation, our strategy based on direct functionalization of a naphthalene ring shortens the route and improves efficiency compared to conventional approaches. This regiospecific approach holds promise for rapid access to diverse derivatives of gossypol for biological studies.