Study on the synthesis of Nebivolol, a-aderenergic blocker

doi:10.16085/j.issn.1000-6613.2016.s2.051

Abstract

Abstract: 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 chiral 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 low-down the cost, simplify the operating procedure, and the yield gets better as well.

Key words: β-anderenergic blocker, Nebivolol, chiral intermediates, synthesis

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。

关键词: β受体阻断药, Nebivolol, 手性中间体, 化学合成

CLC Number:

TQ463

WU Chengjun, MA Yang, LI Na, LÜ Haining, SUN Tiemin. Study on the synthesis of Nebivolol, a-aderenergic blocker[J]. Chemical Industry and Engineering Progree, 2016, 35(S2): 295-300.

吴成军, 马阳, 李娜, 吕海宁, 孙铁民. β受体阻断药Nebivolol的合成工艺[J]. 化工进展, 2016, 35(S2): 295-300.

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