头孢妥仑匹酯的结构确证及方法建立

目的：建立药物头孢妥仑匹酯的化学结构确证方法。方法：采用一维及二维核磁共振谱（NMR）、红外光谱（IR）、质谱（MS）、热重分析（TGA）、差示扫描量热法（DSC）以及X-射线粉末衍射（XRPD）对头孢妥仑匹酯进行结构表征。结果：运用一维和二维的NMR波谱对头孢妥仑匹酯的¹H和¹³C NMR信号进行了全归属和详细的解释，并讨论了H-6与H-7的立体构型以及双键的构型；同时讨论了红外特征吸收峰所对应的官能团的振动形式和质谱的主要碎片离子的可能的裂解方式；对TGA/DSC的检测结果进行了分析，确定了与原料药晶型相关的不同衍射角（2θ）的特征衍射峰。结论：通过实验证实头孢妥仑匹酯的结构为2，2-二甲基丙酰氧甲基（6R，7R）-7-[（Z）-2-（2-氨基噻唑-4-基）-2-甲氧基亚氨乙酰氨基]-3-[（Z）-2-（4-甲基噻唑-5-基）乙烯基]-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸酯。

Objective: To establish a method for the determination of the chemical structure of cefditoren pivoxil. Methods: The structure of cefditoren pivoxil was elucidated by 1D and 2D NMR,IR,MS,TGA,DSC,XRPD. Results: The ¹H and ¹³C NMR chemical signals of the compound were all assigned and interpre ted by 1D and 2D NMR;the stereo-structure of H-6,H-7 and the configuration of double-bond were discussed.Based on the infrared spectra and the mass spectral data,the vibrations of functional groups and the possible fragmentation pathways were also discussed.The test result of TGA/DSC was analyzed,and the diffraction peaks of the different diffraction angles related to the crystal form of API were determined. Conclusion: The chemical structure of cefditoren pivoxil was verified to be methyl (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(Z)-2-(4-methylthiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate through experiments.

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