A practical conversion of natural physostigmine into the potent butyrylcholinesterase inhibitor N-1,N-8-bisnorcymserine

A rapid novel synthetic route to the potent reversible butyrylcholinesteras e inhibitor (-)-N-1,N-8-bis-norcymserine (1) is reported from physostigmine (2) in a 20% total yield. Details on the formation of the imino-quinone 6 obtained in the oxidation of N-1-benzylnoresermethole (4) and its conversio n into N-1-bis-noreseroline (7) are given. As expected, the product of this synthesis, (1), had identical biological activity to the same agent produc ed by total synthesis. (C) 2000 Elsevier Science Ltd. All rights reserved.