A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

Abstract: Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D- and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and g-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (–)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)- lentiginosine.