Synthesis of 5-substituted analogues of huperzine A

Three 5-isosteres of huperzine A (2–4) were first synthesized. The key intermediate 10 was prepared by the reaction of acid 13 with LTA. The compounds 2 and 3 had 50% inhibition by 35 and 47 μM, respectively, which still retained antiacetylcholinesterase activity.