Studies toward the asymmetric total synthesis of mitomycin C

The mitomycins are a structurally unique class of naturally occurring compounds. Nearly all members of mitomycins family have shown broad spectrum antibiotic and potent antitumor activity against tumors resistant to other antineoplastic agents. One particular member of the family, mitomycin C, has been used clinically for cancer chemotherapy because of its broad spectrum activity against solid tumors.; In this dissertation, a novel stereoselective approach to the ring system of the mitomycins is described. The synthesis was based on a convergent strategy involving a stereocontrolled addition of a phenyl silyl enol ether to a pyrroline N-acyliminium ion followed by an intramolecular palladium-catalyzed aryl triflate amination to afford the (9R*,9aR)-tetrahydropyrrolo[1,2- a]indole ring system.; Based on similar strategy, an enantioselective synthesis of the fully functionalized mitosanes and mitosenes were achieved with high efficiency. An approach toward the isomitomycin system and efforts to introduce the key C9a methoxy group are also described.