Epothilones other analogs

Fig. 21 Epothilone dimmer. This dimeric compound by Nicolaou et al. was first detected as a side product in the synthesis of other analogs. It exhibits very potent biological activity (no specific data are available) [40]...

Ixabepilone is currently being marketed by Bristol-Myers Squibb under the trade name Ixempra. Several other analogs of the epothilones are currently undergoing clinical trials for treatment of many different forms of cancer. The next decade is likely to witness several epothilone analogs emerge as new anticancer agents. 

We have seen that the appropriate choice of the catalyst and/or the olefin substitution pattern can dramatically shift the equilibrium in favor of the macrocyclic product. Other factors are important as well, such as the general experimental conditions. Danishefsky and coworkers have highlighted the effects of solvent, temperature, and concentration on the yield of macrocyde RCM for the synthesis of analogs of epothilone 490 [14]. As shown in Scheme 2.4, RCM of compound 7 in... 

In addition to the examples discussed above, many other potent side chain-modified epothilone analogs have been reported in the literature. Major advances in this area have resulted from the collaborative work between the Nicolaou group at the TSRI and the group at Novartis. For example, these groups discovered that pyridine-based analog 22 (Figure 3.5) is equipotent... 

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