维格列汀的合成路线改进  

An improved synthetic route of vildagliptin

作　　者：杨金路 王秋艳[1] 张勇[1,2] 

机构地区：[1]河北科技大学化学与制药工程学院,石家庄050018 [2]河北省药用分子化学重点实验室-省部共建国家重点实验室培育基地,石家庄050018

出　　处：《中国新药杂志》2015年第11期1295-1297,1315,共4页Chinese Journal of New Drugs

摘　　要：目的:改进维格列汀的合成路线。方法:以L-脯氨酸为起始原料,经Boc保护、酰胺化、脱水、脱保护成盐、N-氯乙酰化得(S)-1-(2-氯乙酰基)-2-氰基吡咯烷(2),最后与3-氨基-1-金刚烷醇缩合即得目标产物维格列汀。结果:目标化合物的结构经质谱(ESI-MS)、核磁共振氢谱、碳谱(1H-NMR,13C-NMR)等确证,总收率32%,产品纯度99.8%以上。结论:改进后的工艺操作简单,产率较高,产品纯度高,适合工业化生产。Objective： To improve the synthetic route of vildagliptin. Methods： L-proline was used as the starting material and treated by Boc-protection, amidation, dehydration, deproteetion and N-chloroacetylation to give （S）-1-chloroacetyl-2-cyanopyrrolidine （2） , which was then reacted with 3-amino-1-adamantanol to get the target product vildagliptin. Results： The structure of the target compound was confirmed by MS, 1H-NMR and 13C-NMR. The total yield was 32% , and the product purity was more than 99.8% as shown by HPLC analysis. Conclusion： The improved synthetic process with simplified operation, good yield and high purity is applicable for industrial production.

关 键 词：维格列汀 L-脯氨酸 抗糖尿病药物 合成 

分 类 号：R914.5[医药卫生—药物化学]