【作者】 程培锋；

【导师】 林汉森；

【作者基本信息】 广东药学院 ， 药物化学， 2008， 硕士

【摘要】 黄皮酰胺是从芸香科黄皮属植物黄皮叶的水提取液中分离得到的七种有效成分之一。药理学试验表明天然黄皮酰胺有明显的促智作用,能改善多种原因包括Aβ引起记忆障碍的作用、提高突触效能和新突触形成的作用、提高皮层,海马组织蛋白磷酸酯酶活性,同时研究还发现黄皮酰胺具有能明显降低四氯化碳引起的小鼠高谷丙转氨酶的作用,是很有前途的促智药物和保肝药物。但黄皮酰胺溶解性能较差,难溶于大部分有机溶剂,水溶性也比较差。本文以消旋黄皮酰胺为先导物,对黄皮酰胺的结构进行修饰,设计合成4个酯类目标化合物,均为2位取代酯类黄皮酰胺类化合物,以期能改善其药动学性能,提高其药效。本课题实验内容包括先导物黄皮酰胺的合成和衍生物的合成两部分。先导物的合成参考文献方法,同时对黄皮酰胺酮的分离方法进行了优化。衍生物的合成综合文献方法,考虑到酰化剂的酰化能力、获取途径、副产物等方面的因素,对酰化方法进行了选择。先导物的酰化以对应的酸作为酰化剂,DCC/DMAP为催化剂,同时对酰化反应的反应物料摩尔比,反应温度、反应时间、反应后处理等进行了研究和摸索。先导物合成部分各步所得中间体对其理化性质进行了验证;衍生物合成部分所得2个中间产物及2个目标产物均经IR,1H-NMR,MS,和元素分析确证结构。更多还原

【Abstract】 Clausenamide is isolated from aqueous extract of leaves of Clausena lansium. Base on the Pharmacological study, clausenamide could improve dysmnesia caused by multiagent including Aβ, enhance the efficacy of synapse, promote the formation of the new synapse, raise the activity of the cortex and the protein phosphatase of the Hippocampus and decrease the activity of mice serum ALT caused by CCl4. It can be used as nootropics or liver protectant. However, in water and most organic solvent, the dissolvability of clausenamide was low. Using clausenamide as the lead compound, four target compounds were designed in this article, for obtaining higher pharmacokinetics performance compounds.The synthesis of the lead compound and the derivates of the clausenamide was included in this thesis. Method of clausenamidone’s separation was improved in the synthesis of the lead compound. In terms of ability, price acquisition and coproduct, corresponding organic acids were selected as acylating agents, DCC and DMAP were selected as catalysts. The better reaction routes were definited through studying the effect factor to the acylation reaction, for instance, the molar ratio of the reactant, reaction temperature, reaction time and postprocessing of the reaction, two intermediates and two target compounds were synthesized in the synthesis of the derivates. All of the target compounds were characterized by means of IR, 1H-NMR, MS and elemental analysis.更多还原