| 引用本文: | 张霞,章国龙.托法替尼的结构鉴定与构象分析[J].中国现代应用药学,2019,36(5):542-544. |
| ZHANG Xia,ZHANG Guolong.Structure Determination and Conformational Analysis of Tofacitinib[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(5):542-544. |
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| 摘要: |
| 目的 鉴定合成的托法替尼的化学结构，并对其构象进行分析。方法 用DMSO-d6作溶剂，通过测试该合成样品的1H-NMR、1H-NMR（DMSO-d6+D2O）、13C-NMR（包括常温、高温60℃、高温120℃的图谱）、1H-1H COSY、DEPT、HSQC、HMBC图谱及其关键中间体的常温13C-NMR图谱，参照文献与专著，鉴定合成的托法替尼的化学结构，并分析其构象。结果 确证了合成的托法替尼的化学结构。其常温13C-NMR图谱中，大多数信号出现裂分，升温到120℃，裂分信号合并，推导在常温下，因为围绕酰胺键的旋转受阻，托法替尼在DMSO-d6溶液中以2种构象存在。结论 合成的托法替尼结构正确，且常温下在DMSO-d6溶液中以2种构象存在。 |
| 关键词: 托法替尼 构象 核磁共振 关键中间体 受阻旋转 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.05.006 |
| 分类号:R914.2 |
| 基金项目: |
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| Structure Determination and Conformational Analysis of Tofacitinib |
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ZHANG Xia, ZHANG Guolong
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Huadong Medicine Group Pharmaceutical Research Institute Co., Ltd., Hangzhou 310011, China
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| Abstract: |
| OBJECTIVE To investigate the structure and conformation of synthesized Tofacitinib. METHODS The 1H-NMR,1H-NMR(DMSO-d6+D2O),13C-NMR(at room and elevated temperature of 60 and 120℃), 1H-1H COSY, DEPT, HSQC, HMBC spectra of Tofacitinib and 13C-NMR of its key intermediate at room temperature were recorded in DMSO-d6. Based on the related literature, monograph and the 13C-NMR comparison of Tofacitinib and its key intermediate, the structure and conformation analysis of synthesized Tofacitinib in DMSO-d6 were carried out. RESULTS The structure of synthesized Tofacitinib was determined on the basis of these spectral data. Most of the signals of Tofacitinib in 13C-NMR spectrum at room temperature were split while these split signals were merged when the temperature was increased to 120℃. It maight have two conformations in DMSO-d6 at room temperature due to the restricted rotation about the carbon-nitrogen bond of the amide group. CONCLUSION The structure of synthesized Tofacitinib is confirmed and it may have two conformations in DMSO-d6 at room temperature. |
| Key words: Tofacitinib conformation nuclear magnetic resonance key intermediate restricted rotation |
