Studies of Extended Quinone Methides. Design of Reductive Alkylating Agents Based on the Quinazoline Ring System

Article abstract of DOI:10.1021/jo00261a021

This report discusses the quinone methide reactivity, electrochemistry, and xanthine oxidase alkylation properties of a quinazoline-based reductive alkylating agent.The design of this alkylating agent involved functionalizing the quinazoline ring as a quinone with a leaving group placed so as to afford a quinone methide species upon reduction. pH-rate profiles, nucleophile-trapping studies, and product studies indicate the presence of a steady-state quinone methide species.The quinone methide species reacts by either trapping nucleophiles or ketonizing to a quinone.It is concluded that the fate of this and similar quinone methides can be predicted from the redox potential of the quinone resulting from quinone methide ketonization.If a low potential quinone is the ketonization product, ketonization is thermodynamically favored over nucleophile trapping.The opposite is true if a high redox potential quinone (such as the quinazoline-based system) results from ketonization.Finally, the reductive alkylation of the xanthine oxidase active site is demonstrated with title systems.