Synthesis of C6 and Unsubstituted Analogs of Azridinomitosene Chemotherapies
Aziridinomitosenes (AZMs) are a group of potential anti-cancer compounds that are structurally and functionally similar to the clinically used anti-tumor antibiotic Mitomycin C (MC). Both act by forming cross-links with the DNA of cancerous cells, thereby inhibiting cell replication and resulting in cell death. However, AZMs are not activated via the reductive activation mechanism required for MC, which presumably contributes to MC’s adverse side effects. Previous investigations on AZMs have shown that substituting a methyl group at the C7 electrophilic center increases potency over 140 fold in HL-60 cancer cells. In order to enable further testing, C6-methyl and unsubstituted AZM analogs are being prepared using a 20 step linear approach. Key structural features being incorporated into the compound include a quinone group, a carbamate at C10, and an aziridine ring at C1. Progress accomplished thus far includes the formation of the tetracyclic core, the aziridine ring and installation of the C10 hydroxy group. Additionally, current efforts are focused on the formation of an alternative precursor that will result in a more convergent synthesis, thus reducing the number of steps involved in AZM synthesis. These and other related results will be presented.
Boehmer, Jason and Schwarz, Olivia, "Synthesis of C6 and Unsubstituted Analogs of Azridinomitosene Chemotherapies" (2016). 2016 Undergraduate Research and Scholarship Conference. Paper 76.