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.
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, USA.
Musong
M
Kim
Edwin
E
Vedejs
D001388:Aziridines / Q000138:chemical synthesis*; D003500:Cyclization; D008968:Molecular Conformation; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D001388:Aziridines; D010078:Oxazines; C413848:aziridinomitosene; C112463:FK 317 dihydrobenzoxazine