【作者】 孙小虎；

【导师】 丁运生；

【作者基本信息】 合肥工业大学 ， 材料学， 2009， 硕士

【摘要】 本文介绍了抗生素类药物盐酸克林霉素和克林霉素磷酸酯的药物特性,并对它们合成工艺的发展进行了综述。设计了整条反应路线,经过对盐酸林可霉素7位羟基的氯代、盐酸克林霉素3位和4位羟基的保护、磷酰化、水解,最终得到克林霉素磷酸酯,总收率达到62.7%。本文通过Vilsmeier试剂与盐酸林可霉素直接氯代反应制备盐酸克林霉素。反应液直接碱化、浓缩、醇化得到盐酸克林霉素,收率达到88%。盐酸克林霉素在室温下制备丙叉克林霉素。反应中丙酮同时作为溶剂和羟基保护剂对3、4位羟基进行保护。通过重复对比实验最终确定最佳反应温度、反应物摩尔比以及后处理碱性试剂的选择。收率达到80%。丙叉克林霉素经磷酰化反应、水解反应成功得到最终产物克林霉素磷酸酯。反应过程中以二氧六环取代吡啶作溶剂,以适量吡啶作为有效的催化剂。收率为88%。本文采用傅立叶变换红外光谱和核磁共振光谱对盐酸克林霉素、丙叉克林霉素、克林霉素磷酸酯进行了结构表征及分析。通过高效液相色谱法,建立了盐酸克林霉素和克林霉素磷酸酯及其有关物质含量的测定方法并进行方法学研究。结果表明,按照预期的反应路线合成了总产率为62.7%的克林霉素磷酸酯。更多还原

【Abstract】 This paper introduces the pharmic trait of antibiotic clindamycin hydrochlorid and clindamycin phosphate and discusses the development of their synthesis. The whole reaction route was designed too. The clindamycin phosphate was obtained with 62.7% total yield after 7-hydroxyl of lincomycin hydrochlorid was chlorinated, 3,4-hydroxyl of clindamycin hydrochlorid was protected, osphorylated and hydrolyzed.Clindamycin hydrochlorid can be prepared by the direct chlorination reaction of the Vilsmeier reagent and lincomycin hydrochlorid. After that, the reaction solution was basified, concentrated and alcoholized. The yield reached 88%.Clindamycin 3,4-isopropylidene was synthesized by Clindamycin Hydrochloride at room temperature. During the reaction, acetone was used as a solvent and also a hydroxyl protection reagent to protect 3,4-hydroxyl. After the experiment was repeated for a few times, the optimum reaction condition including temperature, reactant molar ratio and alkaline reagent in the later treatment was fixed. The yield reached 80%.Clindamycin phosphate was successfully prepared by the acylation and hydrolysis reaction of Clindamycin 3,4-isopropylidene. Dilxane was used as solvent in stead of pyridine, and meanwhile, certain amount of pyridine was used as catalyst. The yield reached 88%.In our work, the products were characterized by FT-IR and 1H NMR. The measure methods and research methodology of making sure the content of clindamycin hydrochlorid, clindamycin phosphate and related substance was set up. Clindamycin phosphate with the yield of 62.7% was obtained by following the expected reaction route.更多还原