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1、0 要 -细辛脑是中药石菖蒲中提取出的有效成分。通过对大量文献调查研究，作 者发现 -细辛脑具有多方面的作用。自上世纪 60 年代起，国内外对 -细辛脑即 进行了广泛的研究，已证实其在止咳、祛痰、镇静、抗惊厥等方面具有广泛的生 物学活性。而中草药资源有限，关于 -细辛脑的立体选择性合成问题越来越受到 关注。在此基础上，本文对立体选择性合成 -细辛脑的反应条件进行了深入考察。 本文以 1,2,4-三甲氧基苯为原料，经 Vilsmeier 反应制得 2,4,5-三甲氧基苯甲 醛。首先研究了利用 Wittig 反应合成 -细辛脑，结果表明产率和立体选择性都较 低。然后研究了 Grignard 反应合
2、成 -细辛脑，利用 2,4,5-三甲氧基苯甲醛与乙基 溴化镁反应制得相应的中间体醇，考察了该醇脱水时不同脱水剂对产率和立体选 择性的影响。结果表明采用硫酸铜催化，甲苯恒沸脱水，合成 -细辛脑（2-(E)-1-丙烯基)-1,4,5-三甲氧基苯），立体选择性 93.3%，总产率 80.26%（以醛计）。 由 -细辛脑的合成路线可知，在合成的 -细辛脑中伴有少量的其顺反异构体 -细辛脑，其结构与 -细辛脑相似，但 -细辛脑具有很强的毒性。根据中国药典 0 2000 年版）要求，在合成的 -细辛脑中 -细辛脑的含量应小于 1%。作者分别 采用了 HPLC 法和 GC 法对 -细辛脑的含量进行了测定。对
3、比发现，GC 法较 HPLC 法简便迅速。测定结果表明 -细辛脑的含量符合药典要求。 该方法为 -细辛脑的工业生产提供了一种高效简便的方法。 关键词：-细辛脑、无水硫酸铜、立体选择性、合成、HPLC 法、GC 法author has found thatAbstract-Asarone is the effective ingredient taked out from Acorus gramineus soland. The-Asarone is very useful in different fields after reading a numberof literatures. Int
4、ernal and overseas scientists have studied on -Asarone in the early 1960s. It is found that -Asarone play an essential role in relieving a cough, removing the phlegm, calmless, resisting convulsion. Because Chinese traditional medicine is limited, studies on stereoselective synthesis of -Asarone hav
5、e been paid more and more attention to. This paper will study the condition of stereoselective synthesis of -Asarone.2, 4, 5-trimethoxybenzaldehyde was synthesized from 1, 2, 4-trimethoxybenzene by the Vilsmeier reaction. First, synthesis of -Asarone by Wittig reaction was studied, the result showed
6、 that the yield and stereoselectivity to synthesize -Asarone is lower. Then synthesis of -Asarone by Grignard reaction was studied. The intermediate aromatic alcohol was prepared by the reaction of magnesium ethyl bromide with 2,4,5-trimethoxybenzaldehyde, the catalysis of different dehydrant was ev
7、aluated for the yield and stereoselectivity to synthesize -Asarone. The results showed that -Asarone was stereoselectively obtained with dominant E-stereoselectivity(93.3%) under catalysis of cupric sulfate in dry toluene, the yield was 80.2 % (based on the aromatic aldehyde).From the synthetic rout
8、e of -Asarone, a few -Asarone will be maked with -Asarone. -Asarone whose structure like -Asarone has strong toxicity. The content of -Asarone shouldnt achieve 1% according to the requirement of Chinese pharmacopoeia (2000). The content of -Asarone was mensurated by the method of HPLC and GC. Compar
9、ing the two methods GC is more simple and convenient than HPLC. The result showed that the content of -Asarone reached the requirement of pharmacopoeia.A new simple and efficient proces for the industrial production of -Asarone was provided.Key Words: -Asarone、cupric sulfate、stereoselectivity、Synthe
10、sis、HPLC、GC0 录 第 1 章 绪 论 11.1 -细辛脑简介 1 1.2 -细辛脑的研究进展 2 1.2.1 体内代谢 2 1.2.2 药理作用 4 1.2.3 临床应用 5 1.3 本论文的选题背景及目的 9 第 2 章 2,4,5-三甲氧基苯甲醛的合成及利用 Wittig 反应合成 -细辛脑 11 2.1 引言 11 2.2 2,4,5-三甲氧基苯甲醛的合成 12 2.2.1 合成方法研究 11 2.2.2 实验部分 14 2.2.3 小结 11 2.3 利用 Wittig 反应合成 -细辛脑 15 2.3.1 合成方法研究 12 2.3.2 实验部分 12 2.4 小结 17 第 3 章 1-(2,4,5-三甲氧基苯)-1-丙醇的合成及合成 -细辛脑的脱水剂选择 18 3.1 引言 18 3.2 仪器与药品 19 3.2.1 THF
