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.
Kim
Musong
M
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, USA.
Vedejs
Edwin
E
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