Enantioselective synthesis of a putative hexaketide intermediate in the biosynthesis of the squalestatins

A convergent synthesis of (3R, 5Z, 8E, 10R)-3-hydroxy-8,10-dimethyl-11-phenylundec-5,8-dienoic acid 4, a putative hexaketide intermediate in the biosynthesis of the squalestatins, is described. A key step in the assembly of the carbon framework is the coupling of alkyne 19 with allylic bromide 13 giving, after further functional group manipulations, the target compound as a single diastereomer. The approach may be adapted for the preparation of the corresponding (3S, 5Z, 8E, 10R)-isomer as well as for the incorporation of carbon-13 labels required for biosynthetic studies. (C) 1997 Elsevier Science Ltd.