Bioreductive alkylating agents refers to those compounds which could become potent alkylating agents subsequent to a bioreduction. Quinones are an obvious class of compounds which could function in this manner provided they are functionalized in such a fashion as to give reactive quinone methides upon reduction to the corresponding hydroquinones. Sartorelli has indeed demonstrated this to be a viable hypothesis. Sartorelli's work as well as a complete review of potential bioreductive alkylating agents in the naturally occurring quinone field provides insight regarding those structural features necessary for biological activity. The prime objective is to prepare compounds predicted to be biologically active on the basis of the above analyses. Specifically, alkynylquinones will be utilized to prepare epoxyquinones. Methodology has been developed which suggests a general route to the former; the latter are ideally suited to function as bioreductive alkylating agents. Nanaomycin, mitomycin, and kinamycin are among a list of approximately 200 natural quinones which would be predicted to be bioreductive alkylating agents. Simple compounds related to the above three natural products, and which contain specifically those structural features deemed necessary for activity, will be prepared. Finally, an exploratory study of the chemistry of the previously unknown alkynylquinones will be undertaken.
