β受体阻断药Nebivolol的合成工艺  

Study on the synthesis of Nebivolol,a-aderenergic blocker

作　　者：吴成军[1] 马阳[1] 李娜[1] 吕海宁[1] 孙铁民[1] 

机构地区：[1]沈阳药科大学创新药物研究与设计教育部重点实验室,辽宁沈阳110016

出　　处：《化工进展》2016年第B11期295-300,共6页Chemical Industry and Engineering Progress

摘　　要：为了手性合成新型β受体阻断药Nebivolo,通过对文献路线的分析,基于经济高效的原则,选择了一条合理的合成路线,分别以廉价的维生素C和D-甘露醇作为手性源,通过环合反应的过程生成另一对手性碳。这样得到的非对映异构体,经过结晶得到光学纯的手性中间体,因而解决了结构中的构型问题。总共经过10步反应,成功地对Nebivolol进行了化学合成。改进后的新合成路线总收率12.7%,优化了合成路线,提高了收率,降低了成本,且节能环保。Aim to synthesize Nebivolol, as a new type of β-anderenergic blocker. We choose a rational synthesis route to prepare it. We choose two cheap compounds-Vitamin C and D-Mannitol as one source of chiral carbon. By the ring-closure reaction in the synthesis route, we introduce another two cbiral points and get a mixture of two pseudosymmetric isomers. So we can get optical-pure intermediates by crystallization of the mixture and successfully resolve the problem of configuration. Finally, we complete the synthesis of Nebivolol by 10-step reaction. The overall yield is 12.7%. The synthetic method is also intensively studied and optimized in order to lowdown the cost, simplify the operating procedure, and the yield gets better as well.

关 键 词：Β受体阻断药 NEBIVOLOL 手性中间体 化学合成 

分 类 号：TQ463[化学工程—制药化工]