Concise Enantioselective Total Synthesis of Isopavine Alkaloids

Abstract

Herein, we report a concise asymmetric total synthesis of isopavine alkaloids, which feature a special azabicyclo[3.2.2]­nonane tetracyclic skeleton. The key steps include iridium-catalyzed asymmetric hydrogenation of unsaturated carboxylic acids, Curtius rearrangement, and Eschweiler–Clarke methylation, which enable an enantioselective approach to isopavine alkaloids in 6–7 linear steps. Furthermore, for the first time, isopavine alkaloids, especially (−)-reframidine (3), are found to display effective antiproliferative effects on various cancer cell lines