This program is directed toward the total synthesis of the powerful antifeedant agent azadirachtin (1) isolated from the neem tree whose extracts have been used for centuries as antifungal, antiviral, and antimalarial agents. The daunting nature of this challenging synthetic target invites new strategies for the construction of polycyclic systems and crowded carbon-carbon bonds and promises discovery, invention and development of new synthetic technologies. The designed convergent strategies toward azadirachtin (1) are variants of a general concept involving construction of advanced key building blocks representing the decalin and dihydrofuran domains of the molecule followed by tethering and intramolecular formation of the crowded C8-C14 carbon-carbon bond via radical or organometallic species. The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology.
