Phenserine, a Novel Anticholinesterase Related to Physostigmine: Total Synthesis and Biological Properties

Abstract

Phenserine, the phenylcarbamate analogue of physostigmine , is a drug candidate of potential use for treating Alzheimer's disease. Phenserine inhibits acetylcholinesterase selectively, improves memory dramatically in experimental animals without toxicity, and reduces the production of β-amyloid precursor protein, the source of the Alzheimer's toxin β-amyloid. Phenserine was made from physostigmine in two steps, and it can be prepared in the required optically active form by total synthesis. For this purpose, the oxindole route developed by Julian in his total synthesis of physostigmine was vastly improved. Details of this work performed at the National Institutes of Health and at Institutions sponsored by this agency are presented herein.