Title

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

Document Type

Article

Publication Date

7-2002

Source Publication

Tetrahedron

Abstract

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 (−)-22 and (+)-23. The Mosher's esters of each alcohol were determined to be >90% de. Reaction of (−)-22 with acryloyl chloride, followed by ring closing metathesis gave the dihydro-2-pyrone target (−)-5. Mitsunobu inversion of (+)-23 with p-nitrobenzoic acid, hydrolysis, and esterification with acryloyl chloride and ring closing metathesis gave pseudoenantiomeric segment (+)-6.

Comments

Tetrahedron, Vol. 58, Issue 30 (2002), pp 6009-6018. DOI: 10.1016/S0040-4020(02)00613-0