Total Synthesis and Biological Assessment of Cyclopropane-Based Epothilone Analogues - Modulation of Drug Efflux through Polarity Adjustments

Benzimidazole-based analogues of epothilones containing a cyclopropane ring in place of the natural epoxide moiety have been prepared based on the selective cyclopropanation of homo­allylic alcohol intermediates as one of the key steps. In contrast to the epoxide-containing parent compounds the cyclopropane analogues are not or only minimally susceptible to P-gp170-mediated drug efflux.