Synthesis and Characterization of Stable Isotope Deuterium-Labelled Higenamine

Abstract

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 (1H 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.

Keywords

• higenamine
• stable isotope labelled
• h-d exchange reaction
• ms internal standards