Total Synthesis of Aporphine Alkaloids via Benzyne Chemistry: Progress Towards a Late‐Stage Enantioselective Hydrogenation and Neuroprotective Activity Evaluations

Abstract

AbstractA dehydroaporphine intermediate obtained via benzyne chemistry was used to accomplish the enantioselective total synthesis of (S)‐nuciferine, the first total synthesis of (±)‐urabaine, and our second‐generation total synthesis of lysicamine. (S)‐Nuciferine was obtained by an unprecedented late‐stage asymmetric hydrogenation employing a chiral iridium(I) catalyst. The first total synthesis of (±)‐urabaine and the second‐generation total synthesis of lysicamine, which exhibited low cytotoxicity and neuroprotective activity, were completed by oxidation reactions in 7 and 6 steps, respectively.