Reactivity of aziridinomitosene derivatives related to FK317 in the presence of protic nucleophiles

Article abstract of DOI:10.1021/jo202286a

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 Cs₂CO₃/CD₃OD to give isomeric products where substitution occurred at C(10) and C(9a) (mitomycin numbering) providing a CD₃ ether and a CD₃ 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 ₃CH₂OH/CH₃CN 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.