The epothilones and sarcodictyins have shown to be potent cytotoxic compounds with a Taxol™-like mode of action. The clinical importance of Taxol™ has stimulated intense research into finding compounds with prospective superior chemotherapeutic properties to Taxol™. We have developed enabling synthetic technologies for the construction of combinatorial libraries of these two potentially important chemotherapeutics, which led, in both cases to compounds with superior biological activity.