Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
In order to probe structure-activity relationships in the epothilone area, two series of epothilone B analogues have been designed and synthesized. The first series containing an oxazole moiety in place of a thiazole on the side chain was constructed by utilizing key intermediates 7-9 or 10, 12, and 13 (Scheme 1), whereas the second series containing an ethano group instead of the gem-dimethyl group at position 4 was synthesized from fragments 42 and 43. A Yamaguchi-type macrolactonization reaction was used to construct the macrocycle from a secoacid, which was assembled, in both cases, by means of a) an aldol reaction, b) an Enders alkylation, and c) a Wittig-type reaction. This convergent strategy provided access to oxazole analogues 2,4,29-32 and 4,4-ethano derivatives 3,40,60-63 for biological studies.
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