利托那韦的合成工艺研究

Synthesis of ritonavir

目的对利托那韦的合成工艺进行优化研究,以获得一条适宜于工业化生产的合成工艺路线。方法使用(2S,3S,5S)-2-胺基-3-羟基-5-(叔丁氧羰基胺基)-1,6-二苯基己烷的丁二酸盐作为起始原料,经过酰胺化、氨基脱保护和再酰胺化三步反应,最终制得目标产物利托那韦。结果经过相应的优化研究之后,最终成功地以较高的收率合成了高纯度的利托那韦产品(总收率57%,纯度>99%)。结论获得了一条较优的利托那韦合成工艺路线,该工艺路线具有高效、简洁以及绿色等特点,能够满足工业化生产的需要,具有广阔的应用前景。

Objective To optimize the synthesis of ritonavir,in order to obtain a suitable synthetic routes for industrial production. Methods Ritonavir was finally synthesized via three steps including amidation,deprotection of amine,amidation from （2S,3S,5S）-2-amino-3-hydroxy-5-（tert-butoxycarbonyl amino）-1,6-diphenyl hexane succinate.Results After the study of optimization,ritonavir was synthesized with high yield and high purity （overall yield 57%,purity 〉99%）.Conclusions An efficient,simple,green synthesis route of ritonavir is available,which makes it suitable for industrial production.