简便的13C标记甘氨胆酸的合成方法

A Convenient Method for the Synthesis of 13C labelled Glycocholic acid

摘要:

甘氨胆酸-甘氨酰基-1-13C是一种13C呼吸试剂，可用于临床诊断。本文成功使用简便的方法，“一锅煮”合成13C标记甘氨胆酸。即以氯甲酸异丁酯为活化试剂，甘氨酸-1-13C和胆酸直接缩合制备甘氨胆酸-甘氨酰基-1-13C，合成产品使用HPLC、LC-MS和1HNMR等进行分析。在优化的合成条件，氯甲酸异丁酯：胆酸：甘氨酸：三乙胺=1：1：1：1，反应温度为10℃，反应时间1 h时，13C 标记甘氨胆酸收率80.3%（以甘氨酸-1-13C计）， 13C丰度达99.1% atom 13C，光学纯度99.2%，化学纯度为97.7%。

Abstract:

With isobutyl chloroformate as active agent, Glycocholic acid-glycyl-1-13C, a 13C-breath test substrate and applications in clinical practice, was synthesized by one pot method of condensation of glycine-1-13C directly with cholic acid. 13C labelled Glycocholic acid was characterized by HPLC, LC-MS and 1HNMR. The yield of 13C labelled glycocholic acid was 80.3% (based on glycine-1-13C), with 99.1% atom13C abundance, 99.2% optical purity and 97.7% chemical purity, at optimized conditions, which were n(isobutyl chloroformate) : n(cholic acid) : n(glycine) : n(triethylamine)=1 : 1 : 1 : 1, 10 oC reaction temperature and 1 h reaction time.