维达列汀主要杂质的合成.PDFVIP

维达列汀主要杂质的合成 ? 1 2 彭嘉勋 ，毛雨 (1.湖南工程学院，湖南 湘潭 411101；2.长沙荣光达生物科技有限公司，长沙 410013) 摘要：目的 为了加强抗糖尿病药物维达列汀原料药的质量控制，合成了维达列汀的 3 个特定杂质。方法 维达列汀(1) 经闭环反应制得杂质 A；以杂质 A 为原料经水解反应制得杂质 B；维达列汀(1)经水解反应、酯化反应和闭环反应制得杂 质 B 和杂质 C。结果 合成的 3 种杂质的结构经过 1H-NMR、13C-NMR 和 LC-MS 确证，纯度经 HPLC 检测97%。结论 合成的 3 种杂质可以作为维达列汀原料药质量控制的杂质对照品。 关键词：维达列汀；杂质；合成 中图分类号：R914.5 文献标志码：B 文章编号：1007-7693(2017)04-0527-03 DOI: 10.13748/ki.issn1007-7693.2017.04.011 Synthesis of the Main Impurities of Vildagliptin PENG Jiaxun1, MAO Yu2(1.Hunan Institute of Engineering, Xiangtan 411101, China; 2.Changsha Rongguangda Biological Technology Co., Ltd., Changsha 410013, China) ABSTRACT: OBJECTIVE To conduct the quality control of an oral antidiabetic vildagliptin, three impurities recorded in quality specifications were prepared. METHODS Impurity A was obtained from vildagliptin(1) by ring-closure reaction. Impurity B was generated in impurity A by hydrolytic reaction. Impurity B and impurity C could be also synthesized from vildagliptin(1), via hydrolytic reaction, esterification and ring-closure reaction. RESULTS The chemical structures of the three impurities were confirmed by LC-MS, 1H-NMR and 13C-NMR. The purities were 97% as determined by HPLC. CONCLUSION The synthesized impurities can be used as the standard substances in the quality control of vildagliptin. KEY WORDS: vildagliptin; impurity; synthesis 维达列汀(vidagliptin，1)，商品名为 Galvus， 维达列汀耐受性良好，具有保护胰岛 β 细胞和改 化学名为(S)-1-[2-(3-羟基金刚烷-1-氨基)乙酰基] 善延缓胃排空等优良特点[7]。 吡咯烷-2-甲氰，是由诺华公司开发的一种高选?? 维达列汀及其有关化合物的专利将于 2019 年 性、竞争性的二肽基肽酶-4(dipeptidyl peptidase 到期，而目前国内并无对应的仿制药。因此，维 Ⅵ，DPP-4)抑制剂，能