DNA alkylation properties of CC-1065 and duocarmycin analogs incorporating the 2,3,10,10a-tetrahydrocyclopropa(d)benzo(f)quinol-5-one alkylation subunit: identification of subtle structural features that contribute to the regioselectivity of the adenine N3 alkylation reaction

The adenine N3 alkylation is mediated by additional characteristics that resemble the imposed stereoelectronic control. Reactive 2,3,10,10a-tetrahydrocyclopropa(d)benzo(f)quinol-5-one (CBQ)-based agents alkylate same sites as the corresponding DSA-, CPI-, DA-, and CI-based agents. These agents have less selectivity among the established alkylation sites and low efficiency to alkylate DNA. Adducts obtained from adenine N3 addition to the least substituted cyclopropane carbon were detected under the relevant conditions of limiting agent.