Synthetic studies directed toward the phorboxazoles: preparation of the C3–C15 bisoxane segment and two stereoisomers

A synthetic approach to the C3–C15 segment of the cytotoxic marine metabolite phorboxazoles is described. This segment consists of a methylene linked bisoxane structure. The first pyran ring was constructed by a Lewis acid catalyzed diene–aldehyde cyclocondensation. The β-C-glucoside substitution pattern of this ring was established by a stereoselective allylation. Ozonolysis of vinyl group and enantioselective allylation of the racemic aldehyde generated two separable homoallylic alcohols and . The Mosherʹs esters of each alcohol were determined to be >90% de. Reaction of with acryloyl chloride, followed by ring closing metathesis gave the dihydro-2-pyrone target . Mitsunobu inversion of with p-nitrobenzoic acid, hydrolysis, and esterification with acryloyl chloride and ring closing metathesis gave pseudoenantiomeric segment .