阿戈美拉汀有关物质的合成及滔罗定水溶液含量的测定

发布时间：2019-05-28 02:48

【摘要】：阿戈美拉汀是一种褪黑激素的萘类衍生物,化学名为N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺。阿戈美拉汀基本对所有类型的抑郁症均有较好的治疗效果,且副作用较少,是更有前景的抗抑郁药物。而控制药物的纯度,是保证药物安全有效的重要前提,保证杂质的含量是控制药物纯度,也是控制药物安全、有效的重要因素。目前,我们已经合成了阿戈美拉汀的四个有关物质。分别为2-(7-甲氧基-1-萘基)乙胺化合物,2,2,-二(7-甲氧基-1-萘基)二乙胺化合物,2,2,-二(7-甲氧基-1-萘基)二乙酰胺化合物,2-((7-甲氧基-3,4-二氢-1-萘基)乙基)乙酰胺化合物。其中伯胺化合物以7-甲氧基-3,4-二氢-1-萘酮为原料经过与氰乙酸加成,DDQ脱氢,再经Li Al H4还原生成。仲胺化合物以7-甲氧基-3,4-二氢-1-萘酮为原料经过与氰乙酸加成,DDQ脱氢,再经雷尼镍催化氢化反应生成。仲胺乙酰胺化合物是在合成仲胺化合物的基础上经过酰胺化反应生成。2-((7-甲氧基-3,4-二氢-1-萘基)乙基)乙酰胺化合物以7-甲氧基-3,4-二氢-1-萘酮为原料经过与氰乙酸加成,经Li Al H4还原,再经酰胺化反应生成。滔罗定是一种广谱抗菌药,临床上可用于多种感染疾病的治疗,其对临床应用具有重要作用。滔罗定良好的杀菌和抗内毒素作用,是因为其在水溶液中水解为滔罗安、甲醛的性质。我们采取两种方法对滔罗定水溶液含量进行测定。分别为分光光度计法、高效液相色谱法。其中分光光度计法采用变色酸捕获甲醛,高效液相色谱法采用柱前衍生化手段,分别使用丹磺酰氯,萘磺酰氯将滔罗定水溶液分解的滔罗安片段衍生化,生成可被检测的产物,再进行含量测定。
[Abstract]:Agomelatine is a Naphthalene derivative of melatonin, the chemical name is N-[2-(7-methoxyl-1-Naphthyl) ethyl] acetamide. the chemical name is N-[2-(7-methoxy-1-Naphthyl) ethyl] acetamide. Agomelatine is a more promising antidepressant because of its good therapeutic effect on all types of depression and less side effects. Controlling the purity of drugs is an important prerequisite to ensure the safety and effectiveness of drugs. Ensuring the content of impurities is not only an important factor to control the purity of drugs, but also an important factor to control the safety and effectiveness of drugs. At present, we have synthesized four related substances of Agomelatine. 2-(7-methoxy-1-Naphthyl) ethylamine compound, 2, 2, bis (7-methoxy-1-Naphthyl) diethylamine compound, 2, 2,-bis (7-methoxy-1-Naphthyl) diacetamide compound, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2. 2-(7-methoxy-3, 4-dihydro-1-naphthyl) acetamide compound. The primary amine compound was prepared from 7-methoxy-3, 4-dihydro-1-Naphthalene ketone by addition with cyanoacetic acid, dehydrogenase by DDQ, and then reduced by Li Al H4. The secondary amine compound was synthesized from 7-methoxy-3, 4-dihydro-1-Naphthalene ketone by addition with cyanoacetic acid, DDQ dehydrogenation and catalytic hydrogenation of Raney nickel. The secondary amine acetamide compound is formed by amidation on the basis of the synthesis of secondary amine compound. 2-(7-methoxy-3, 4-dihydro-1-naphthyl) acetamide compound with 7-methoxyl-3, 4-bis Hydrogen-1-Naphthalene ketone was added with cyanoacetic acid as raw material. It was reduced by Li Al H 4 and then aminated to form. Torodin is a kind of broad-spectrum antibacterial drug, which can be used in the treatment of many kinds of infectious diseases, and plays an important role in clinical application. Torodin has good bactericidal and anti-endotoxin effects because of its hydrolysis to Toluoan and formaldehyde in aqueous solution. We used two methods to determine the content of Tonodin aqueous solution. They were spectrophotometry and high performance liquid chromatography (HPLC). Among them, formaldehyde was captured by discoloration acid by spectrophotometer, and Danesulfonyl chloride and naphthalene sulfonyl chloride were used to derivatize the surroan fragment decomposed by Danzuloyl chloride and Naphthalene sulfonyl chloride, respectively, to form a product that could be detected. Then the content was determined.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914;R927.2

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