癫痫病治疗药托吡酯中两个杂质的合成

Synthesis of two impurities of anti-epilepsy drug topiramate

目的合成癫痫病治疗药托吡酯的两个特定杂质(N-甲基托吡酯和2,3-二羟基托吡酯)以加强该药的质量控制。方法以D-果糖为起始原料,经缩合、氯磺酰化、甲胺化等反应合成一特定杂质N-甲基托吡酯;以托吡酯为起始原料,经酸水解反应合成另一杂质2,3-二羟基托吡酯。结果合成了托吡酯中两个特定杂质,并通过高分辨质谱、核磁共振氢谱等方法进行了结构鉴定。结论合成的两个杂质可作为托吡酯质量控制的杂质对照品。该合成方法反应条件温和、原料易得、操作简单。

Topiramate is an important drug for the treatment of epilepsy. To improve the quality control of topiramate two specified impurities ,N-methyltopiramate and 2,3-dihydroxyl topiramate were synthesized. N- methyltopiramate was synthesized from D-fructose through condensation, sulfonyl formation reaction and methylamine substitution reaction. 2,3-Dihydroxyl topiramate was synthesized by an acid-catalyzed hydroly- sis from topiramate. And their structures were identified by HR-MS and 1H-NMR. The two specified impuri- ties can be used as the reference substance of the related substances in the quality control of topiramate. The reaction conditions were mild and the raw materials were cheap and easy to obtain.