稳定同位素氘标记的去甲乌药碱的合成与表征

Synthesis and Characterization of Stable Isotope Deuterium-Labelled Higenamine

为了快速准确地检测去甲乌药碱的含量,采用稳定同位素内标试剂与同位素稀释质谱法相结合的检测技术,以2-(3,4-二甲氧基苯)乙腈为起始原料,经过碱催化氢-氘同位素交换、还原、皮克特-施彭格勒(Pictet-Spengler)环化反应、脱保护基等关键反应步骤,得到稳定同位素氘标记的去甲乌药碱。该合成方法简单成熟,原料廉价易得,副反应少。该产物经核磁共振(^(1)H NMR)和高分辨质谱(HRMS)表征确认,氘同位素丰度大于96%,适合作为质谱内标试剂用于去甲乌药碱的定性定量分析。

Stable isotope labelled internal standards combined with isotope dilution mass spectrometry can offer an analytical method with strong anti-interference capability,good accuracy and precision for the detection of higenamine.A novel deuterium-labelled higenamine was synthesized from 2-(3,4-dimethoxyphenyl)acetonitrile.The synthesis procedure featured key steps such as hydrogen-deuterium exchange,reductive,Pictet-Spengler cyclization,and deprotection.The synthesis method had the advantages of cheap and easily available starting materials,less side reactions,and high isotope abundance.The deuterated product was confirmed by proton nuclear magnetic resonance(^(1)H NMR)and high-resolution mass spectrometry(HRMS)characterization with more than 96% deuterium isotope abundance,which can be used as stable isotope-labelled MS internal standards for qualitative and quantitative analysis.