Stereocontrolled synthesis of lepadiformine A

Abstract

In this paper we present results of a study into whether the tricyclic core of the lepadiformines A–C can be accessed via intramolecular hetero-Diels–Alder cycloaddition. We are able to demonstrate that such a process is possible and that the reaction proceeds in an endo-selective fashion, providing the correct relative stereochemistry for this family of natural products. By employing this approach we have been able to develop a short (7 step) synthesis of (±)-lepadiformine A, starting from commercially-available trans-2-nonenal.