【作者】 庞雪；

【导师】 王道武；

【作者基本信息】 长春工业大学 ， 生物化工， 2011， 硕士

【摘要】 本文以具有共同的异喹啉环结构的小檗碱、黄连碱、巴马汀和药根碱所组成的黄连混合生物碱为起始原料,经过总碱的还原加氢、甲氧基、亚甲二氧基的羟基化、邻位羟基的环合和氧化脱氢四步反应合成黄连碱,总收率可达16%。通过单因素实验设计,详细研究了由黄连混合生物碱制备单体黄连碱的工艺条件,比较了由混合生物碱制备黄连碱的两种工艺条件的优劣,确定了最佳工艺条件；并以白色念珠菌、金黄色葡萄球菌、克柔念珠菌及隐球菌为实验菌株,测定了制备黄连碱和天然黄连碱的最低抑菌浓度MIC值。实验得到的最佳工艺条件：黄连混合生物碱先加氢再脱甲氧基、亚甲二氧基,然后邻位的羟基环合最后脱氢得到单体黄连碱。四氢黄连混合生物碱的合成条件：还原剂硼氢化钠与原料的在室温条件下的反应摩尔比为4：1,反应时间4 h,甲醇的浓度为80%。四氢四羟基黄连碱的合成条件：三溴化硼与中间体的反应摩尔比为6：1,反应时间为14 h。四氢黄连碱的合成条件：反应温度120℃,反应时间为30 h,溴氯甲烷与原料的反应摩尔比为6：1,氟化铯与原料的反应摩尔比为10：1。黄连碱的合成条件：催化剂用醋酸钠,碘与原料的反应摩尔比为3：1,反应时间10 h。抗菌结果表明：制备黄连碱保持甚至提高了抗菌性能。其中,制备的单体黄连碱对金黄色葡萄球菌具有较高的抗菌活性,MIC值为8μg/mL。其抗菌机理可能是由于制备产物具有更高的亲脂性,增强了药物对细胞膜的渗透性。本文制备黄连碱的方法与传统的黄连碱的制取方法相比,省去了药物合成中原料的纯化步骤,且将药力分散不明、纯度低的粗黄连混合碱转化为了抗菌专属性更高、活性更强的单体黄连碱；该方法操作简便,成本低廉,适合黄连碱的批量生产,具有广阔的工业应用前景,并可为其它中草药的研究提供借鉴,对于提高中草药的利用价值和发展创制新药具有很好的指导意义,为其实际应用提供基础。更多还原

【Abstract】 Coptisine in overall yield of 16% was synthesized from the alkaloids with the same main structure of isoquinoline included berberine, berberurine, palmatine and jatrorrhizine by a four-step reaction of hydro genati on, demethylation or demethylene-dioxy, cyclization, dehydrogenation and so on.Through the single-factor experimental design, the synthetic conditions of Coptisine were studied. The conditions were compared with the two process. The optimum process conditions were obtianed. Candida albicans, Staphylococcus aureus, Candida krusei and Cryptococcus were for the experimental bacterium.The value of minimum inhibitory concentration is tested.The optimal conditions for the experiment are as follows:alkaloids first were hydrogenated and then demethoxy and demethylenedioxy to obtain the monomer coptisine after the final dehydrogenation of the hydroxyl ring. The conditions for synthesis tetrahydroberberine alkaloids:the most appropriate molar ratio of the sodium borohydride and raw materials is 4:1 and the reaction time is 4 h, using anhydrous potassium carbonate as catalyst and the appropriate methanol solution concentration was 80%.. The conditions for the synthesis of tetrahydrotetrahydroxy coptisine is that the most appropriate molar ratio of borontribromide and the intermediates is 6:1, reaction time is 14 h. The temperature of the tetrahydrocoptisine synthesis is 120℃and the reaction time is 30 h; the most appropriate molar ratio of bromochloromethane and the intermediates is 6:1. The molar ratio of catalys and the intermediates is 10:1.And the reaction time of coptisine synthesis is 10 h. the most appropriate catalys is sodium acetate.The results of the antibacterial show that:the prepared coptisine monomer maintain or even improve the antibacterial properties. The prepared monomer coptisine has, a high antibacterial activity for Staphylococcus aureus, the value of MIC is 8μ/mL. The mechanism of their antibacterial may due to that the prepared product has higher lipophilic and enhance the permeability of the drug on the cell membrane.The method which used in this article compared with the conventional method of prepareing coptisine eliminated the purification of the raw materials used for the drugs synthesis, and at the same time it contraved the mixture of bases into monomer coptisine which has higher antimicrobial specificity and activity.This method was simple and easy to operate.The cost was low and suitable for coptisine’s mass production.The transformation of the main components to one component would provide useful ideas for the Chinese herbal medicine’s value and good guide for the development of new medicine.更多还原