A practical conversion of natural physostigmine into the potent butyrylcholinesterase inhibitor N1,N8-bisnorcymserine

A rapid novel synthetic route to the potent reversible butyrylcholinesterase inhibitor (−)-N1,N8-bisnorcymserine (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 N1-benzylnoresermethole (4) and its conversion into N1-bisnoreseroline (7) are given. As expected, the product of this synthesis, (1), had identical biological activity to the same agent produced by total synthesis.