【作者】 姚强；

【导师】 邢永恒；

【作者基本信息】 辽宁师范大学 ， 无机化学， 2013， 硕士

【摘要】 头孢类抗生素药物是临床上应用非常广泛的抗感染性药物，头孢呋辛钠和头孢呋辛酯的抗菌效好，毒副作用低，是国内外常见的抗菌类药物。其中（Z）-2-甲氧亚氨基-2-呋喃乙酸铵盐（SMIA）是合成头孢类药物头孢呋辛钠和头孢呋辛酯的重要侧链。本文通过条件实验在原有的实验基础上进行了一定的改进，以乙酰呋喃为原材料，先制备出2-氧代-2-呋喃乙酸，再与甲氧胺盐酸盐进行肟化反应，得到（Z）-2-甲氧亚氨基-2-呋喃乙酸铵盐。实验表明，在制备2-氧代-2-呋喃乙酸时，亚硝酸钠的滴加时间、反应温度以及pH的变化等方面对实验结果有着重大影响，本文通过一系列条件试验，严格控制亚硝酸钠的滴加时间、反应温度以及pH的大小，最终使得产物的综合产率达到了58.9%，对我国药物的工业生产以及生活具有重大意义。近些年，药物共晶作为一个新兴的课题越来越受到人们的关注，其在医疗，医药，生物化学等方面的贡献也越来越重要，随着晶体工程学，超分子合成化学的快速发展，药物晶体形势的发展也受到越来越多的关注。本文通过对药物活性成分的分析，成功的合成药物共晶三氟柳-4,4，-联吡啶。药物共晶的合成包括溶剂蒸发法、碾磨法、超临界流体法等，合成的新型化合物药物共晶对药物的理化性质，如稳定性、熔点、溶解性、引湿性、代谢稳定性、分散速率、溶出速率、药物缓释等方面都有所改善。药物共晶的合成，对医疗卫生行业的作用不可言喻，相信产品的生产也指日可待。更多还原

【Abstract】 Cephalosporin drugs are clinically very extensive application anti-infectives medicine inparticular, cefuroxime sodium and cefuroxime axetil antibacterial effect are good, low toxicand side effect, it is a commonly used at home and abroad of antibacterial drugs. The (Z)-2-methoxy imino furan ammonium acetate (-2-SMIA) is an important intermediate species ofthe synthesis of cephalosporins cefuroxime sodium and cefuroxime axetil chain.In this paper, through the synthetic technics conditions in the experiment on the basis ofthe original materials hace been improved,namely,using acetyl furan as raw material, preparedthe2-oxo-2-furan acetic acid, then oximation reaction and methoxyamine hydrochloride,was (Z)-2-methoxy imino furan acetic acid ammonium salt-2-was prepared. Experimentsresults show that, in the preparation of2-oxo-2-furan acetic acid, sodium nitrite additiontime, reaction temperature and pH changes,etc, have significant effects on the experimentalresults. In this paper we eventually made comprehensive yield of product reach55%bycontrolling sodium nitrite reaction time, reaction temperature and pH values through a seriesof experiments which is of great significance for industrial production and life.In recent years, the cocrystal is a new subject for more and more attention, in the medical,pharmaceutical, chemical and biological aspects, it is more and more important for thecontribution of life. With the rapid development of the crystal engineering of supramolecularchemistry, development of drug crystal situation also received more and more attention. Inthis paper, through the analysis of the active pharmaceutical ingredient, we have successfulsynthesis of three fluorine-4,4，-bipyridine pharmaceutical cocrystals.Synthesis includes solvent evaporation method,the cocrystal grinding method,supercritical fluid method et al. Physicochemical properties of drugs affected by the noveleutectic compounds, such as stability, melting point, solubility, hygroscopicity, metabolicstability, rate of dispersion, solubility, drug delivery have been improved. Synthesis ofpharmaceutical cocrystals is ineffable for effect of medical and health industry, trustingproducts also point the day and await for it.更多还原