Total Synthesis of an Epothilone Analogue Based on the Amide-Triazole Bioisosterism

Epothilones are 16-membered macrolides that act as microtubule-targeting agents to tackle cancer. Exploiting the amide-triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too.