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.

Key words

Clausena alkaloids - ζ-clausenamides - balasubramides - benzo[d]azocinones - eight-membered lactams - ring expansion

Publication History

Received: 31 January 2023

Accepted after revision: 24 February 2023

Article published online:
12 April 2023

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