替米考星的合成

论文编号:CL112  论文字数:16563,页数:35

摘要：
 替米考星是大环内酯类畜禽专用抗生素。最初是由美国礼来公司开发成功，近年来国内销售呈起步上升趋势。本文以磷酸泰乐菌素为起始原料，通过水解、与3，5-二甲基哌啶反应生成替米考星。拟对替米考星的反应条件进行优化，以期提高它的收率。
 通过实验，找到了较优的反应条件，从而得到较好的产率。反应的第一步是酸水解，加入适量浓硫酸调节其溶液的pH在1.4-1.7之间，反应时间1h，反应温度35℃，水解后得到的产率在98%以上；脱糖泰乐菌素与3，5-二甲基哌啶以及催化剂甲酸的摩尔比例为1∶1.1∶1.5较为合适，反应温度70℃，反应时间2 h，在此反应条件下产率可以达到89%。
 在这个实验中，我们发现,除杂质的后处理过程也非常重要，活性炭脱色的效果直接影响产物的析出；在保持晶体颗粒问题中也发现了NaOH浓度对晶体形状的影响。
 关键词：磷酸泰乐菌素；替米考星；大环内酯；水解；HPLC。
 
Abstract:
 Tilmicosin is a semi-synthetic macrolide antibiotics specially used in animal, which first developed by LiLai company and has a increasing sale at home recently. We use Tylosin phosphate as the primal material, through hydrolyzing, then react with the 3,5- methyl piperidine to synthesize Tilmicosin.
 Through this experiment, we find the optimum reaction conditions, and thus increasing the output. The first step of the reaction is acid hydrolyzing, adding proper sulfuric acid to regulate the pH between 1.4-1.7, reacting 1 hour, Temperature 35℃,and the yields is above 98% after hydrolysis. The suitable molar ratio of the Desmycosin and 3,5-Methyl Piperidine and Acid is 1∶1.1∶1.5, the reacting time is 2 hour ,and the suitable reacting tempeture is 70℃.Eventually we get the product in 89% rate in this condition.
 In this experiment, we found that the disposing of impurities in the after-treatment process is also very important. Activated Carbon Decolorizing is a direct factor on the precipitation of product; We also discovered that the concentration of NaOH can affect the shape of the crystal in maintaining granular crystal process.
 Keywords: Phosphoric acid Tylosin, Tilmicosin, Macrocyclic lactone, Hydrolysis, PLC.
 
目  录
中文摘要 I
英文摘要 II
目录 III
1. 绪论 1
 1.1  化学结构 1
 1.2  背景 1
 1.2.1 作用机理 1
 1.2.2 抗菌活性 2
 1.2.3 药动学 2
 1.2.4 残留 2
 1.2.5 毒性 3
 1.3 文献综述 3 
2. 实验部分 6
 2.1 脱糖泰乐菌素的制备 6
 2.1.1  概述 6
 2.1.2  实验试剂与实验仪器 6
 2.1.3  反应过程 6
 2.1.4  实验步骤 7
 2.1.5  反应小结 7
 2.2 替米考星的制备 8
 2.2.1  概述 8
 2.2.2  实验试剂与实验仪器 8
 2.2.3  反应过程 8
 2.2.4  实验步骤 8
 2.2.5  反应小结 9
  2.3  分析方法 9
 2.3.1  流动相试剂 9
 2.3.2  分析条件 9
 2.3.3  替米考星含量测定 10
    2.4 反应条件优化 10
        2.4.1 单因素的选择 10
        2.4.2 反应条件优化 11
        2.4.3 实验结果数据处理 12
3. 结果与讨论 14
4．总结与展望 15
致谢 17
参考文献 18
附录A 文献翻译 20