Reactivity of aziridinomitosene derivatives related to FK317 in the presence of protic nucleophiles.
The syntheses and reactivity of N-TBDPS and N-trityl protected derivatives of an aziridinomitosene corresponding to FK317 are described. New reactivity patterns were observed for these highly sensitive and functionally dense heterocycles under mild nucleophilic conditions approaching the threshold for degradation. Thus, the silyl or trityl protected aziridinomitosene reacted with Cs(2)CO(3)/CD(3)OD to give isomeric products where substitution occurred at C(10) and C(9a) (mitomycin numbering) providing a CD(3) ether and a CD(3) hemiaminal, respectively. These findings show that heterolysis at C(10) is faster than at aziridine C(1), in contrast to the behavior of typical aziridinomitosenes in the mitomycin series. The labile N-TBDPS hemiaminal and the more stable N-trityl hemiaminal resemble the mitomycin K substitution pattern. A reagent consisting of CsF in CF(3)CH(2)OH/CH(3)CN desilylated a simple N-TBDPS aziridine but caused nucleophilic cleavage at C(1) as well as C(10) without cleavage of the N-TBPDS group in the fully functionalized penultimate aziridinomitosene. The high reactivity of the C(10) carbamate with nucleophiles precludes the use of deprotection methodology that requires N-protonation for fully functionalized aziridinomitosenes in the FK317 series.
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, USA.
Susan D
SD
Wiedner
Edwin
E
Vedejs
D001388:Aziridines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry*
D001388:Aziridines; D010078:Oxazines; C413848:aziridinomitosene; C112463:FK 317 dihydrobenzoxazine