Synthesis of an ABC Ring Analogue of Kapurimycin A3 as an Effective DNA Alkylating Agent

With a 5′-GPu-3′ sequence selectivity that is very similar to that of the natural antitumor antibiotic kapurimycin A3 (1), the ABC ring analogue 2 effectively cleaves DNA by guanine alkylation. Essential for cleavage activity are the reactive alkenyl epoxide group in the side chain and the strong intercalation of the aromatic units of 1 and 2 in the DNA duplex; this was made clear by the significantly lower activity of an AB ring analogue.