Recent developments in the chemistry, biology and medicine of the epothilones

The epothilones have occupied center stage on the scenes of total synthesis, chemical biology and medicine for the last five years, no doubt because of their intriguing mode of action and unusually high potency against tumor cells, including multidrug-resistant cell lines. This article highlights the most recent advances within this exciting field. Thus, an overview of recent synthetic endeavors culminating in a new generation of total syntheses and analogues, some with higher potencies than the naturally occurring substances, will be given, and the chemical biology, in particular the current understanding of structure-activity relationships of the epothilones, will also be discussed in light of the latest biological results. In addition, the recently elucidated biosynthetic machinery of the natural epothilone-producing myxobacterium Sorangium cellulosum, as it is now understood, will be described. Finally, some preclinical and clinical studies will be summarized.