Intramolecular Reductive Heck Approach to Guaipyridine Alkaloids

The guaipyridine alkaloids are a family of compounds that all share an unusual carbon structure, whose source plants have been used as a traditional medicine in Southeast Asia. Members of the guaipyridine family include cananodine and the rupestines. Cananodine has been isolated from the fruits of the Canaga odorata in Indonesia, Malaysia and the Philippines. Cananodine has been used of decades as a traditional medicine for the treatment of malaria, infections and fever. Studies of cananodine’s biological activity have reveled activity against Hep G2 and Hep 2,2,15 human hepatocarcinoma cell lines, the most common types of liver cancer. Due to the similarities in structure, there is strong evidence to suggest that other members of the guaipyridine alkaloid family will have anti-cancer activity. Progress toward the synthesis of the guaipyridine skeleton using an intramolecular Heck reaction will be presented along with a nearly complete synthesis of rupestine D.