头孢洛林酯中间体的合成方法研究

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1、No.20092854河北医科大学硕士研究生毕业论文头孢洛林酯中间体的合成方法研究研究生:杜立民导师:杜玉民教授专业:药物化学二级学院:药学院研究日期:2009年9月-2012年3月提交日期:2012年3月万方数据目录中文摘要····································································································1英文摘要·································

2、···································································4研究论文头孢洛林酯中间体的合成方法研究前言····································································································7材料与方法························································

3、································7结果···································································································19附图···································································································22讨论··········

4、·························································································28结论···································································································31参考文献·····················································

5、······································31综述头孢菌素类抗生素研究进展·······················································34万方数据致谢···········································································································45个人简历·····················

6、··············································································46万方数据中文摘要头孢洛林酯中间体的合成方法研究摘要金黄色葡萄球菌是一种常见的革兰氏阳性球菌，可引起化脓性感染、肺炎、伪膜性肠炎等局部感染，甚至脓毒血症、败血症等全身性感染。上世纪四十年代青霉素诞生，有效的控制了金黄色葡萄球菌所引发的感染。一些金黄色葡萄球菌能产生β-内酰胺酶，对青霉素耐药，甲氧西林可有效治疗此类金黄色葡萄球菌的感染。1961

7、年耐甲氧西林的金黄色葡萄球菌(MRSA)在英国首次发现，此类菌株致病性强，耐药性严重，所引发的感染逐步蔓延流行，发病率迅速增加，成为临床严重的致病菌。根据世界疾病预防控制中心的调查，每年因MRSA严重感染死亡的患者有9000人左右，病人全身感染病死率高达50%；临床上金黄色葡萄球菌的感染中MRSA占20-50%，某些医院甚至高达80%以上，其中医院获得型感染和社区获得型感染越来越普遍，严重威胁着人类的生命健康。MRSA的治疗是十分棘手的难题，菌株对除万古霉素外的现有抗菌药物，如氨基糖苷类、β-内酰

8、胺类、磺胺类、大环内酯类、喹诺酮类等抗生素均有不同程度的耐药。第四代头孢菌素例如头孢唑兰、头孢噻利等对MRSA虽有一定的抗菌活性，但不能满足治疗需要。万古霉素强烈的毒副作用使部分病人无法耐受，并且临床上已经出现了耐万古霉素的金黄色葡萄球菌(VRSA)。此外，我国抗生素存在大量不规范使用，导致MRSA感染流行强度较高，防治形势非常严峻。因此，发展新一代抗MRSA药物迫在眉睫。MRSA对β-内酰胺类抗生素的耐药机制为细菌基因突变产生的高分子量、低亲和力的青霉素结合蛋白(PBP)2a与β