原位制备8-氘代奥美拉唑钠

Preparation of 8-Deuterium-substituted Omeprazole Sodium in situ

奥美拉唑分子中的氮原子质子化,对邻近的碳核产生有效的电四极矩驰豫,使邻近碳核信号加宽或消失,以致奥美拉唑在DMSO-d6或DMSO-d6/D2O溶液中的碳谱(13CNMR、DEPT-90、DEPT-135)及碳-氢相关谱(HMQC、HMBC)具有非典型的特征,即部分碳原子不出峰且峰形很差,以致无法确定具体的碳数,延长脉冲重复时间无改观。本实验通过将奥美拉唑与NaOH的D2O溶液反应原位制备8-氘代奥美拉唑钠,使吡啶氮原子去质子化,从而使部分不出峰的碳核信号变窄或重又出现,顺利地完成了8-氘代奥美拉唑钠上述谱图的采集,间接地解决了奥美拉唑的碳谱分析,因而提供了一种可通用的测试苯骈咪唑类质子泵抑制剂碳谱及其二维相关谱的方法。

The protonation of N-atom on pyfidine ring led to a kind of strange 13 C NMR spectrum of omeprazole which exhibited less carbon peaks and far from satisfactory peak shape in the solvents of DMSO-d6 or DMSO-d6 ＋ D2O compared with expected and little improvement can been yielded even through adjusting the relaxation delay. In this work, 8-D- substituted omeprazole has been prepared in situ by mixing a solution of NaOH in DMSO-d6 ＋ D20. It makes deprotonation of the N-atom on the omeprazole, the normal ^13C NMR has been obtained. It provides a simple and practical method to record ^13C NMR and two-dimensional NMR of the omeprazole. The method also provides an alternative procedure for studying on the ^13C NMR of omeprazole-like proton pump inhibitors.