Multistep synthesis epothilone

The feasibility of multistep natural product total synthesis via solid-phase methodology, and its application to combinatorial chemistry, was first demonstrated by Nicolaou and coworkers in epothilone synthesis and in the generation of an epothilone library [152]. The traceless release of TBS-protected epoC 361 by RCM of resin-bound precursor 360 (Scheme 69) is an early and most prominent example for the strategy outlined in Fig. 11a. 

Without a doubt, this synthesis constitutes a triumph for the utility of supported reagents and scavenging techniques for multistep complex molecule assembly. The high stereoselectivity and overall yield in this synthesis of epothilone A compares well with the best of all of the previous and conventional routes. By the discussed route, the target molecule was dehvered in 29 steps, with the longest linear sequence being only 17 steps from readily available materials. 

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