This project aims to synthesize a C7-ethyl modified aziridinomitosene (AZM) for future studies of its anticancer and antibiotic activity. The origin of the project stems from the toxic anti-cancer drug mitomycin C (MC), which is the structural model for C7-ethyl analog. Previous studies involving related AZMs and MC indicate that the source of the AZMs' anti-cancer properties originates from their ability to form interstrand DNA crosslinks that lead to programmed cell death. Significantly, the substitution pattern at the C7 position on the AZM quinone ring has been shown to dramatically influence anticancer activity, thus prompting the current research. The C7-ethyl analog is fabricated by means of a twenty-plus step sequence that proves challenging as a result of early formation of a sensitive aziridine ring. Thus far, the synthesis has converted commercially available butyl vinyl ether to �-ethyl-?-butyrolactone via a three step sequence. The butyrolactone was subsequently converted, over the course of 6 reactions steps, to a 2,5-disubstituted oxazole that contains the N-methyl aziridine ring present in the final desired AZM. To finish the compound requires protecting group manipulation and addition of an alkynyl group that will serve as a dipolarophile in the azomethine ylide cycloaddition sequence that will ultimately generate the AZM tetracyclic core. Details of these and all relevant results completed thus far will be discussed.

Progress toward the synthesis of a C7-ethyl aziridinomitosene

247th National Meeting (2014)

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