【摘要】 石杉碱甲（１）是从中草药石杉属植物千层塔（ＬｙｃｏｐｏｄｉｕｍｓｅｒｒａｔｕｍＴｈｕｎｂ．）中分得的一种高效可逆的乙酰胆碱酯酶抑制剂，临床试验证实它对早老性痴呆症有显著疗效。本文报道Ｎ－甲基吡啶酮石杉碱甲类似物２和３的合成。２－甲氧基－５－甲氧羰基－１１－亚甲基－５，９－甲撑环辛－７－烯并吡啶（９）在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮１０，再用甲醇钠和碘甲烷甲基化得Ｎ－甲基吡啶酮１１，１１经碱性水解，Ｃｕｒｔｉｕｓ重排和氨基的脱保护得Ｎ－甲基吡啶酮石杉碱甲类似物２。通过类似的途径从中间体２－甲氧基－５－甲氧羰基－７－甲基－１１－酮－５，９－甲撑环辛－７－烯并吡啶（１４）合成了类似物３。类似物２和３的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。更多还原

【Abstract】 Huperzinc A(1),an alkaloid isolated from the Chinese folk medicine Huperziaserrata, is a potent and reversible inhibitor of acetylcholinesterase.Clinical trials have confirmed thathuoerzine A is effective in the treatment of senile dementia including Alzheimer’s disease.In thispaper the synthesis of N-methyl pyridone analogues 2 and 3 of huperzine A is reported.The selective deprotection of intermediate 9 with chlorotrimethylsilane and sodium iodide inacetonitrile gave a quantitative yield of pyridone 10, which was regioselectively converted to N-methyl pyridone 11 in 94% yield with sodium methoxide and iodomethane.Hydrolysis of ester 11,followed by medified Curtius rearrangement and TMSI- promoted decarbomethoxylation affordedanalogue 2.Similarly,analogue 3 was prepared by using methacrolein instead of acrolein in Michael-Aldol condensations. The acetylcholinesterase inhibitory activities of analogues 2 and 3 were found to be much weakerthan that of huperzine A.更多还原