Synthesis of (±)-10,10-dimethylhuperzine A — a huperzine analogue possessing a slower enzyme off-rate

The synthesis of (±)-10,10-dimethylhuperzine A is reported together with its kinetic (kon and koff) and dissociation constants for the inhibition of fetal bovine serum acetylcholinesterase. While somewhat more potent than (±)-hyperzine A, the dimethyl analogue shows a slower off-rate from AChE, a result that may be of potential therapeutic value.