替米考星的合成

材料科學(xué)論文編號:CL112  論文字?jǐn)?shù):16563,頁數(shù):35 
目  錄
中文摘要 I
英文摘要 II
目錄 III
1. 緒論 1
 1.1  化學(xué)結(jié)構(gòu) 1
 1.2  背景 1
 1.2.1 作用機(jī)理 1
 1.2.2 抗菌活性 2
 1.2.3 藥動學(xué) 2
 1.2.4 殘留 2
 1.2.5 毒性 3
 1.3 文獻(xiàn)綜述 3 
2. 實(shí)驗部分 6
 2.1 脫糖泰樂菌素的制備 6
 2.1.1  概述 6
 2.1.2  實(shí)驗試劑與實(shí)驗儀器 6
 2.1.3  反應(yīng)過程 6
 2.1.4  實(shí)驗步驟 7
 2.1.5  反應(yīng)小結(jié) 7
 2.2 替米考星的制備 8
 2.2.1  概述 8
 2.2.2  實(shí)驗試劑與實(shí)驗儀器 8
 2.2.3  反應(yīng)過程 8
 2.2.4  實(shí)驗步驟 8
 2.2.5  反應(yīng)小結(jié) 9
  2.3  分析方法 9
 2.3.1  流動相試劑 9
 2.3.2  分析條件 9
 2.3.3  替米考星含量測定 10
    2.4 反應(yīng)條件優(yōu)化 10
        2.4.1 單因素的選擇 10
        2.4.2 反應(yīng)條件優(yōu)化 11
        2.4.3 實(shí)驗結(jié)果數(shù)據(jù)處理 12
3. 結(jié)果與討論 14
4．總結(jié)與展望 15
致謝 17
參考文獻(xiàn) 18
附錄A 文獻(xiàn)翻譯 20

摘要：
 替米考星是大環(huán)內(nèi)酯類畜禽專用抗生素。最初是由美國禮來公司開發(fā)成功，近年來國內(nèi)銷售呈起步上升趨勢。本文以磷酸泰樂菌素為起始原料，通過水解、與3，5-二甲基哌啶反應(yīng)生成替米考星。擬對替米考星的反應(yīng)條件進(jìn)行優(yōu)化，以期提高它的收率。
 通過實(shí)驗，找到了較優(yōu)的反應(yīng)條件，從而得到較好的產(chǎn)率。反應(yīng)的第一步是酸水解，加入適量濃硫酸調(diào)節(jié)其溶液的pH在1.4-1.7之間，反應(yīng)時間1h，反應(yīng)溫度35℃，水解后得到的產(chǎn)率在98%以上；脫糖泰樂菌素與3，5-二甲基哌啶以及催化劑甲酸的摩爾比例為1∶1.1∶1.5較為合適，反應(yīng)溫度70℃，反應(yīng)時間2 h，在此反應(yīng)條件下產(chǎn)率可以達(dá)到89%。
 在這個實(shí)驗中，我們發(fā)現(xiàn),除雜質(zhì)的后處理過程也非常重要，活性炭脫色的效果直接影響產(chǎn)物的析出；在保持晶體顆粒問題中也發(fā)現(xiàn)了NaOH濃度對晶體形狀的影響。
 關(guān)鍵詞：磷酸泰樂菌素；替米考星；大環(huán)內(nèi)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.