论文部分内容阅读
目的：光学活性（－）１甲基石杉碱甲的合成及其乙酰胆碱酯酶抑制活性的研究。方法：从光学纯的（５Ｓ，９Ｒ）５出发，经Ｗｉｔｉｇ反应和双键异构化得化合物６。用三甲基氯硅烷和碘化钠选择性脱保护得吡啶酮７后，用甲醇钠和碘甲烷选择性Ｎ甲基化得８，经酯水解、Ｃｕｒｔｉｕｓ重排和脱保护合成了光学活性１位氮上甲基取代的石杉碱甲类似物１１。结果：类似物１１的乙酰胆碱酯酶抑制活性低于石杉碱甲。结论：１甲基能影响类似物１１和蛋白活性之间形成氢键的作用，因此降低其抑制活性。
Objective: To study the synthesis of optically active (-) 1methyl huperzine A and its inhibitory activity on acetylcholinesterase. Methods: Starting from optically pure (5S, 9R) 5, Wittig6 and Wittig6 were isomerized by Witig reaction and double bond. Selective deprotection with trimethylchlorosilane and sodium iodide gave pyridone 7, which was selectively N-methylated with sodium methoxide and methyl iodide 8 to synthesize optical activity via ester hydrolysis, Curtius rearrangement and deprotection 1-methyl-substituted huperzine A analog 11. Results: Analog 11 had lower acetylcholinesterase inhibitory activity than huperzine A. CONCLUSION: 1-Methyl can affect the effect of hydrogen bond between analog 11 and protein activity, thus reducing its inhibitory activity.