The Epothilones and Related Analogues-A Review of Their Syntheses and Anti-Cancer Activities

E.   Blake   Watkins; Amar   G.   Chittiboyina; Jae-Chul      Jung; Mitchell   A.   Avery

doi:10.2174/1381612053764742

Abstract

The macrocylic polyketide class of compounds known as the epothilones has generated substantial interest over the last few years in the areas of chemistry, biology, and medicine due to their interesting structure and, more importantly, their activity against numerous cancer cell lines, including drug-resistant, especially Taxol®-resistant, cancer cell lines. To date, numerous total syntheses have been published, hundreds of epothilone analogues have been synthesized, and detailed structure activity relationship studies have been conducted. The purpose of this review is to give a brief summary of the latest advances made concerning the epothilones. Recent total or partial syntheses will be presented along with the syntheses of new epothilone analogues and their corresponding biological data. In addition, we will look at the current state of research into an economically viable method for the biosynthesis of the epothilones and related analogues.

Keywords: chemotherapy, taxol, epothilone analogues, double-diastereoselective aldol condensation, horner-wadsworth-emmons conditions, epoxidation, macrolactonization, chelation-controlled addition, duthalers allylation, ring closing metathesis (rcm)