The epothilones are the latest in a series of potent microtubule binding agents that have found clinical application in the treatment of a variety of carcinomas. It has been shown that the epothilones share the same b-tubulin binding pocket as the taxanes, and thus much interest has been directed towards elucidating the bioactive conformation and orientation of epothilone within this site. Our contribution towards these efforts has been the synthesis of a series of epothilones analogues that incorporate a photo-affinity label (PAL). Thus, this presentation will outline the design, synthesis and evaluation of the two C4 photo-affinity analogues 1 and 2. In addition, we will discuss our recent synthesis of alkene 3 and our subsequent efforts to synthesize photo-affinity label 4 via phosphine-free Heck reactions (Figure 1).  

Figure 1.