INVITED REVIEW - PHENSERINE, A NOVEL ANTICHOLINESTERASE RELATED TO PHYSOSTIGMINE - TOTAL SYNTHESIS AND BIOLOGICAL PROPERTIES

Phenserine, the phenylcarbamate analogue of physostigmine, is a drug c andidate of potential use for treating Alzheimer's disease. Phenserine inhibits acetylcholinesterase selectively, improves memory dramatical ly in experimental animals without toxicity, and reduces the productio n of beta-amyloid precursor protein, the source of the Alzheimer's tox in beta-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 Instit utions sponsored by this agency are presented herein.