Stereoselective total synthesis of dinemasone A by double intramolecular hetero-Michael addition (DIHMA)

Abstract

The first total synthesis of dinemasone A, a bioactive metabolite with a spiroketal moiety, is described. The main strategy for the construction of the spiroketal unit involves a double intramolecular hetero-Michael addition (DIHMA) of an ynone moiety. The thus obtained axial–equatorial mono anomeric spiroketal, on spiroepimerization with ZnBr₂, was converted into the requisite axial–axial double anomeric spiroketal. The ynone moiety with four stereocentres, was prepared from a chiral propargylic alcohol (C5–C11 fragment) and a dihydroxy aldehyde (C1–C4 fragment), which in turn were obtained from D-mannitol and crotyl alcohol respectively.