稳定同位素氘标记盐酸曲托喹酚的制备

Preparation of Stable Isotope Deuterium Labeled Tretoquinol Hydrochloride

以2-(3,4,5-三甲氧基苯基)乙酸为起始原料,经过脱甲基、酰胺化、甲基化、比希勒-纳皮拉尔斯基(Bischler-Napieralski)环化反应、还原、脱保护基等关键反应步骤,得到稳定同位素氘标记的盐酸曲托喹酚。该合成方法原料廉价易得、简单成熟,目标产物氘同位素丰度较高。该产物经核磁共振氢谱(^(1)HNMR)和高分辨质谱(HR-MS)表征确认,氘同位素丰度为99.9 atom%D,适合作为同位素标记质谱内标试剂用于曲托喹酚的定性定量分析。

A novel deuterium labelled tretoquinol hydrochloride was synthesized from 2-(3,4,5-trimethoxyphenyl) acetic acid via the steps of demethylation,amidation,alkylation,Bischler-Napieralski cyclization reaction,reductive,and deprotection.The synthetic route has the advantages of cheap,accessible starting materials and high isotope abundance.The deuterium-labelled product was confirmed by nuclear magnetic resonance(^(1)HNMR) and high-resolution mass spectrometry(HR-MS) characterization with 99.9 atom% D deuterium isotope abundance,which can be used as stable isotope-labeled MS internal standards for qualitative and quantitative analysis.