TOTAL SYNTHESIS OF OXAZOLE-CONTAINING AND CYCLOPROPANE-CONTAINING EPOTHILONE-A ANALOGS BY THE OLEFIN METATHESIS APPROACH

For structure-activity relationship studies, two series of epothilone A (1) analogues have been designed and synthesized, one containing an oxazole moiety instead of the thiazole heterocycle and the other conta ining a spirocyclopropane moiety in place of the gem-dimethyl group at position C-4 (4,4-ethano-epothilones). The olefin metathesis strategy in solution was utilized for the chemical synthesis of these compound s starting with key building blocks 7-9 for the oxazole series (compou nds 2, 14-18, 21-26) and building blocks 8, 30, and 31 for the 4,4-eth ano series (compounds 3, 39-43, 46-51), The convergent strategy toward s the designed epothilone A series involved a) an aldol condensation r eaction, b) an esterification reaction, c) an olefin metathesis reacti on catalyzed by [RuCl2(=CHPh)(PCy3)(2)], and d) epoxidation of the mac rocycle double bond.