Design of a cyclopropyl quinone methide reductive alkylating agent

Described herein is the formation of a cyclopropyl quinone methide species by leaving group elimination from an indole-based hydroquinone. This species is structurally related to the A-ring of CC-1065 and is a nucleophile trap. In addition, the cyclopropyl quinone methide species can trap or eliminate a proton. Unlike the A-ring of CC-1065, stereoelectronic factors favor opening of the fused cyclopropane ring so as to result in ring expansion. Also described herein is the utility of C-13 NMR spectroscopy in following the fate of the cyclopropyl quinone methide species. Finally, the cyclopropyl quinone methide species reversibly alkylates the guanine N(7) position of DNA, resulting in cytotoxicity.