An efficient route to triene synthons for putative intermediates in polyether antibiotic biosynthesis

Abstract

Current research to establish the late stages of polyether antibiotic biosynthesis via polyepoxide cyclization cascades, as formulated by Cane, Celmer, and Westley, requires the availability through synthesis of relevant putative triene intermediates. The development of practical synthetic methodology to one such triene system is reported in this paper. A synthesis of the triene building block (4) has been accomplished from inexpensive starting materials, using in a key step a modification of the Julia-Lythgoe olefination reaction. Thus the sulphone (8) was prepared in 14 steps from geranyl bromide, in an overall yield of 23%. The optically pure ester (9) was derived from meso-2,4-dimethylglutaric anhydride in four steps with an overall yield of 17%. The sulphone (8) was coupled efficiently with the ester (9), and the coupled product was subsequently transformed into the triene (4).