摘要
目的改进HIV蛋白酶抑制剂利托那韦的合成工艺。方法以L-苯丙氨酸为原料,经三苄基保护、还原性缩合及格氏试剂偶联、α,β-不饱和酮还原、Boc保护、选择性脱苄基、缩合、脱Boc基、再次缩合得到利托那韦。结果与结论目标化合物的结构经~1H-NMR、^(13)C-NMR和MS谱确证,总收率为73.3%(以L-苯丙氨酸计),HPLC法测定纯度达99.8%。与文献报道的工艺相比,该路线操作简易、成品质量好、生产成本较低,有利于工业化生产。
The synthetic route for the preparation of HIV protease inhibitor ritonavir was improved with a series of successive steps,including the protection of L-phenylalanine by tribenzylation, reductive condensa- tion, coupled reaction by Grignard reagent, reduction reaction of α ,β-unsaturated ketone, Boc protection, and deprotection of selective benzyl, followed by condensation, Boc deprotection as well as recondensation. The structure of the obtained product was further characterizated by 1H-NMR, 13C-NMR and MS. The overall yield of the product could be achieved as high as 73.3% in this way ,together with a high purity of 99.8%, detected and confirmed by HPLC. Compared with traditional technologies, this low-cost synthetic approach for high-quality product was operated easily, which was suitable and promising for industrial production.
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2018年第1期29-33,共5页
Chinese Journal of Medicinal Chemistry
基金
辽宁百千万人才工程项目(【2015】2号)
辽宁省博士启动基金项目(201501139)
沈阳市科学技术计划项目(F16-179-9-00)
