Synthesis of (+)-8-Deoxyvernolepin and Its 11,13-Dihydroderivative. A Novel Reaction Initiated by Sulfene Elimination Leads to the 2-Oxa-cis-decalin Skeleton

Abstract

The title compounds are interesting candidates for antifungal screening. This paper describes the enantiospecific synthesis of these compounds starting from (+)-costunolide isolated from a commercially available extract. We used two novel reactions as key synthetic steps in this work: the acid-induced cyclization of an delta,epsilon-epoxy ester, which stereoselectively gave a hydroxymethyl-substituted delta-lactone, with the hydroxyalkyl group in the desired beta-equatorial disposition, and a reaction cascade, initiated by a base-promoted sulfene elimination, which led to a 10-oxiranyl-2-oxa-cis-decalin from the mesylate of a trans-fused delta-lactone. We also found that the reaction between selenium dioxide and the 1,5-diene system of elemanolides gave selenadecalins analogous to natural eudesmanolides. Our results prove that the synthetic strategy employed, on the basis of biomimetic concepts, is a useful procedure for the enantiospecific preparation of (+)-vernolepin-related compounds from accessible germacrolides.