A series of 12 alpha ,13 alpha -aziridinyl epothilone derivatives were synt
hesized in an efficient manner from epothilone A. The final semisynthetic r
oute involves a formal double-inversion of stereochemistry at both the C12
and C13 positions. All aziridine analogues were tested for effects on tubul
in binding polymerization and cytotoxicity. The results indicate that the a
ziridine moiety is a viable isosteric replacement for the epoxide in the ca
se of epothilones.