Synthesis of Clausena Alkaloids Using Unique Ring Expansion of Dihydroisoquinolines and Their Cholinesterase Inhibitory Activity

Abstract

A facile and direct synthetic entry to the carbon skeleton of Clausena alkaloids, the benzo[d]azocin-4-one, is reported featuring the ring expansion of 1-phenyldihydroisoquinoline derivatives initially triggered by oxazolone under environmentally benign conditions in a one-pot procedure. Functionalization of the eight-membered lactam framework provided a set of Clausena alkaloid derivatives. Some derivatives show a promising inhibition toward acetylcholinesterase and a better selectivity index than the previously used Alzheimer’s disease (AD) drug, tacrine, and the currently used AD drug, galantamine.