碳青霉烯类抗生素关键中间体4-AA合成路线的工艺优化
发布时间：2018-10-30 20:41
【摘要】：碳青霉烯类抗生素是一类抗菌能力强、抗菌谱广的抗生素药物,现如今这种药物的应用日益广泛,同时市场需求量也逐步增长,而这类抗生素并不在自然界中天然存在,不能通过提取的方式获得,因此这类药物的化学合成方法广受关注。 4-AA是一种重要的合成关键中间体,是碳青霉烯类抗生素化学全合成的必需原料,因而近年来它的市场价格也在逐步攀升。由于其合成难度大,工业化生产困难,因此如何低成本、高产率地合成4-AA,已成为碳青霉烯类抗生素开发的重中之重。 本实验以L-苏氨酸为出发物,经过6步反应得到最终产物4-AA。从重氮化反应、C3-C4环合反应、羟基保护反应、脱保护反应、Baeyer-Villiger氧化反应这五个部分对反应温度、反应环境、反应溶剂、催化剂等条件进行优化改进,以合理地降低反应成本、提高4-AA的产率,同时提供一条合理可行、绿色环保、简捷高效的工业化生产路线。 改进后得到4-AA的总产率为25.4%,产物重结晶后的纯度可达99.5%以上,所得产物通过核磁共振氢谱(1H-NMR)进行了表征,熔点、旋光度也进行了检验。
[Abstract]:Carbapenem antibiotics are a class of antimicrobial drugs with strong antibacterial ability and wide antibacterial spectrum. Nowadays, the application of carbapenem is becoming more and more extensive, and the market demand is also increasing, and these antibiotics do not exist naturally in nature. Cannot be obtained by extraction, so the chemical synthesis method of this kind of medicine has attracted much attention. 4-AA is an important intermediate of synthesis, and it is an essential raw material for the chemical synthesis of carbapenem antibiotics. Therefore, the market price of 4-AA has been rising gradually in recent years. It is difficult to synthesize 4-AAs in low cost and high yield, so it has become the most important problem in the development of carbapenem antibiotics. In this experiment, L-threonine was used as the starting material, and the final product 4-AA was obtained after 6 steps of reaction. Diazotization reaction, C3-C4 cyclization reaction, hydroxyl protection reaction, deprotection reaction and Baeyer-Villiger oxidation reaction were optimized and improved under the conditions of reaction temperature, reaction environment, reaction solvent, catalyst and so on. In order to reduce the reaction cost reasonably, improve the yield of 4-AA, and provide a reasonable and feasible, green environmental protection, simple and efficient industrial production route. The total yield of 4-AA was 25.4%, the purity of the product after recrystallization was over 99.5%. The product was characterized by 1H-NMR, and the melting point and optical rotation were also tested.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914
本文编号：2301123
[Abstract]:Carbapenem antibiotics are a class of antimicrobial drugs with strong antibacterial ability and wide antibacterial spectrum. Nowadays, the application of carbapenem is becoming more and more extensive, and the market demand is also increasing, and these antibiotics do not exist naturally in nature. Cannot be obtained by extraction, so the chemical synthesis method of this kind of medicine has attracted much attention. 4-AA is an important intermediate of synthesis, and it is an essential raw material for the chemical synthesis of carbapenem antibiotics. Therefore, the market price of 4-AA has been rising gradually in recent years. It is difficult to synthesize 4-AAs in low cost and high yield, so it has become the most important problem in the development of carbapenem antibiotics. In this experiment, L-threonine was used as the starting material, and the final product 4-AA was obtained after 6 steps of reaction. Diazotization reaction, C3-C4 cyclization reaction, hydroxyl protection reaction, deprotection reaction and Baeyer-Villiger oxidation reaction were optimized and improved under the conditions of reaction temperature, reaction environment, reaction solvent, catalyst and so on. In order to reduce the reaction cost reasonably, improve the yield of 4-AA, and provide a reasonable and feasible, green environmental protection, simple and efficient industrial production route. The total yield of 4-AA was 25.4%, the purity of the product after recrystallization was over 99.5%. The product was characterized by 1H-NMR, and the melting point and optical rotation were also tested.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914
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相关期刊论文 前3条
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