Raltegravir的合成工艺研究（英文）

基金项目: 国家高技术研究发展计划 ( 863 计划)资助项目 (No. 2006AA020602 )

Improved synthesis of raltegravir

摘要: 目的：研究治疗获得性免疫缺陷综合症药物raltegravir的合成工艺。方法：经过成氨基腈，苄氧羰基保护氨基，从腈成氨肟，环合成二羟基嘧啶，氮甲基化，微波催化成酰胺，脱保护，再经酰化缩合成酰胺等8步反应制备raltegravir。结果：经过对合成工艺的改进得到了目标产物，其结构经¹H NMR，^{13C NMR，LR-MS和HR-MS确证，总收率为12.0%。结论：此方法原料易得、操作简单、成本低。}
- HIV-1整合酶 /
- raltegravir /
- 合成 /
- 工艺研究
Abstract: Aim ：To develop a practical synthetic route of raltegravir，a drug for HIV treatment. Methods ：Raltegravir was synthesized through an eight-step process including aminonitrile formation，protection with benzyloxycarbonyl group，conversion of the nitrile to the amidoxime，cyclization to form hydroxypyrimidinone，N-methylation，amidation with microwave-assistance，deprotection，amidation with acyl chloride. Results ：The overall yield of the eight-step synthesis is about 12.0% and the structure of the target compound was confirmed by ¹H NMR，^{13C NMR，LR-MS and HR-MS. Conclusion ：The reported synthetic process of raltegravir highlights the advantages in terms of readily available starting materials，convenient operation and low cost.}
- HIV-1 integrase /
- raltegravir /
- synthesis /
- process research