【摘要】 ２－甲氧基－６－羟基－７，８－二氢－５－喹啉羧酸甲酯（２）与２－甲基丙烯醛的不对称Ｍｉｃｈａｅｌ反应是石杉碱甲全合成的关键一步。在０．１当量奎宁的存在下，（２）与２－甲基丙烯醛在室温反应１０ｄ，得到收率大于９０％的立体异构体混合物（３），将（３）甲磺酰化后，再进行消除反应，得到（５Ｓ，９Ｒ）（＋）－（５），总收率约为５０％，对映体过量百分率（ｅｅ值）约为５２％，如果以０．１当量奎尼丁作催化剂，得到约为４０％ｅｅ的（５Ｒ，９Ｓ）－（－）－（５）．最后从（５Ｓ，９Ｒ）－（＋）－（５）得到（－）－石杉碱甲。更多还原

【Abstract】 The key step in the asymmetric total synthesis of optically active huperzine A was the asymmetric Michael addition of methyl 2-methoxy-6-hydroxy-7,8-dihydro-5-quinolinecarboxylate (2) to methacrolein. We found cinchona alkaloids could be used as catalysts.In the presence of quinine (0.1 equiv.),(2) reacted with methacrolein at room temperature for 10 days to give a stereoisomeric mixture (3), which was transformed to olefine (5S,9R)-(+)-(5) by mesylation with mesyl chloride, and then elimination with DBU,NaI in DMF at 100～110℃. The ee value of (5S,9R)-(+)-(5) assigned by 1HNMR analysis in the presence of Eu(hfc)3 was about 52%, After recrysktalization from CH2Cl2-petroleum ether,the (5S,9R)-(+)-(5) (about 65% ee) was obtained in the mother liquor.If quinidine (0.1 equiv.) was used as a catalyst,(5R,9S)-(-)-(5) (about 40% ee) was obtained by a similar procedure.The (5R,9S)-(+)-(5) (about 65% ee) was converted to (-)-huperzine A by a modified known method for the synthesis of(±)-huperzine A.(-)-Huperzine A thus obtained had an optical rotation[α]D=-94.2°(c 0.5, CHCl3), and identical reported spectroscopic data with those of natural and (±)-huperzine A.更多还原