New syntheses of rac-huperzine A and its rac-7-ethyl-derivative.: Evaluation of several huperzine A analogues as acetylcholinesterase inhibitors

rac-Huperzine A, its rac-7-ethyl-derivative and two regioisomeric analogues have been prepared through synthetic sequences involving the elaboration of the pyridone ring in a late stage, by reaction of an intermediate pyrrolidine enamine with propiolamide, which gave mixtures of regioisomeric pyridone derivatives; The acetylcholinesterase inhibitory activity of these and two other recently described 11-unsubstituted huperzine A analogues was determined, the rac-7-ethyl analogue of huperzine A being the most active compound, although it is about 12-fold less active than (-)-huperzine A. (C) 2000 Elsevier Science Ltd. All rights reserved.