合成路线1

A new synthesis of huperzine A has been described: The cyclization of 6-hydroxy-2-methoxy-7,8-dihydroquinoline-5-carboxylic acid methyl ester (I) with 2-methylene-1,3-propanediol diacetate (II) by means of palladium diacetate and triphenylphosphine in dioxane gives the tricyclic ketone (III), which is treated with ethyl triphenylphosphonium bromide and butyllithium in THF to yield the corresponding (Z)-ethylidene derivative (IV). Isomerization of (IV) with AIBN and thiophenol in hot toluene affords the (E)-isomer (V), which is hydrolyzed with NaOH to the free acid (VI). The reaction of acid (VI) with diphenyl phosphorazidate and triethylamine gives the carbamic acid ester (VII), which is finally deprotected and isomerized to huperzine A with trimethylsilyl bromide in refluxing CHCl3, followed by a treatment with trifluoromethanesulfonic acid in hot dioxane.