Synthesis and biological activity of novel epothilone aziridines

[GRAPHICS] 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.