A synthetic approach toward the proposed tetracyclic aziridinomitosene derived from FK317.

A synthesis of the FK317 derivative 25 is described using internal Michael addition. Tin-lithium exchange of the deuterated stannylaziridine 18 generated the key lithioaziridine intermediate, followed by cyclization and aromatization of the pyrrole ring to give 7. Ester reduction from 7 to 23 was effected via temporary aldehyde protection as the silylimidazole adduct 22, and conversion to the carbamate 25 was carried out using FmocNCO and FMOC cleavage. Structure 25 is the N-trityl-protected derivative of the proposed intermediate from bioactivation of FK317 that is responsible for DNA cross-linking. Attempted nitrogen deprotection of 25 using MsOH/i-Pr(3)SiH resulted in replacement of the C(10) carbamate by hydride. Deprotection of the more stable 21 gave the desired aziridine 26.