Synthesis of Aziridinomitosene Anticancer Analogs That Vary at the C6/C7 Positions

TL;DRAbstract

Mitomycin C (MC) is a naturally occurring anti-cancer therapy that has historically seen extensive use as a treatment for a wide variety of cancer types. However, MC’s utility has been greatly diminished as a result of severe side effects, such as delayed myelosuppression. We have prepared and studied structurally similar compounds, called aziridinomitosenes (AZMs), that have similar anticancer activity but may be operating by a mechanism different than that of MC. Both MC and AZMs alkylate DNA to form interstrand cross-links (ICLs) that inhibit DNA replication and lead to cell death. In contrast to MC, the AZMs contain electrophilic centers at the C6 and/or C7 positions that are thought to play a role in the observed increased cytotoxicity in a number of cancer cell types. The present study aims to investigate the importance of these sites by preparing analogs that have methyl, ethyl, butyl, phenyl, or benzyl groups at one or both of these positions. The synthesis of each target molec

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