Diastereodivergent Synthesis of the Quinolizidine-Indolizidine Alkaloids of the Leontidine/Camoensine Family

Abstract

Leontidine and camoensine, the main representatives of the small quinolizidine-indolizidine alkaloid subgroup, are characterized by an inner bispidine system to which a 2-pyridone and a pyrrolidine are fused on opposite sides. We efficiently synthesized both natural products from the commercially available and abundant alkaloid cytisine, which was converted into the key intermediate, N-Boc-11-oxocytisine, by iodine oxidation and protection. Grignard addition, Paal-Knorr type cyclization, and hydrogenation delivered endo-pyrrolidine fused leontidine, while the reversed reaction order, viz. reduction, Sakurai allylation, and ring closure, afforded exo-pyrrolidine annulated camoensine. Hydrogenation and deoxygenation of the pyridone moieties provided four further alkaloids, tetrahydroleontidine, camoensidine, 11-epileontidane and leontidane. In addition, the artificial alkaloid isoleontidine, carrying an endo-fused pyrrolidine on the same side as the pyridone, was prepared from C-13 oxidized cytisine.