| 引用本文: | 王亚静,柴奇,王可心,张龙,韩维娜,裴月湖.苯磺顺阿曲库铵合成工艺的优化[J].中国现代应用药学,2020,37(19):2344-2348. |
| WANG Yajing,CHAI Qi,WANG Kexin,ZHANG Long,HAN Weina,PEI Yuehu.Optimization of Synthesis Process of Cisatracurium Besylate[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(19):2344-2348. |
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| 苯磺顺阿曲库铵合成工艺的优化 |
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王亚静1,2, 柴奇2, 王可心2, 张龙2, 韩维娜2, 裴月湖1,2
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1.沈阳药科大学, 沈阳 110016;2.哈尔滨医科大学, 哈尔滨 150081
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| 摘要: |
| 目的 优化苯磺顺阿曲库铵的合成工艺。方法 以3，4-二甲氧基苯乙胺和3，4-二甲氧基苯乙酸为原料，依次经酰化、脱水环化及还原反应制得四氢罂粟碱。采用半量拆分法，以D-（+）-二对甲基苯甲酰酒石酸为拆分剂，将四氢罂粟碱外消旋体拆分得到R-四氢罂粟碱。再通过麦克尔加成，氮甲基化等反应得到苯磺顺阿曲库铵。结果 目标产物的结构通过质谱、核磁共振氢谱和碳谱进行了确证，纯度经HPLC检测为99.18%，总产率为24.79%。结论 优化后的合成工艺具有反应条件温和、操作简便和反应产率高的优点，为工业化生产提供了参考。 |
| 关键词: 合成 工艺优化 苯磺顺阿曲库铵 D-(+)-二对甲基苯甲酰酒石酸 |
| DOI：10.13748/j.cnki.issn1007-7693.2020.19.008 |
| 分类号:R914.4 |
| 基金项目:黑龙江省博士后科研启动基金（LBH-Q15111） |
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| Optimization of Synthesis Process of Cisatracurium Besylate |
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WANG Yajing1,2, CHAI Qi2, WANG Kexin2, ZHANG Long2, HAN Weina2, PEI Yuehu1,2
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1.Shenyang Pharmaceutical University, Shenyang 110016, China;2.Harbin Medical University, Harbin 150081, China
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| Abstract: |
| OBJECTIVE To optimize the synthesis process of cisatracurium besylate. METHODS Using 3,4-dimethoxyphenethylamine and (3,4-dimethoxyphenyl) acetic acid as starting material, tetrshydropapaverine was prepared by acylation, dehydration cyclization and reduction reaction. The semi-quantitative method was used to obtain R-tetrshydropapaverine with (+)-Di-1,4-toluoyl-D-tartaric acid as resolving agent. Then cisatracurium besylate was synthesized by michael addition reaction and methylation reaction. RESULTS The structure of the target product was confirmed by MS, 1H-NMR, and 13C-NMR. The HPLC indicated that the purity of product was 99.18%, and the total yield was 24.79%. CONCLUSION The optimized process have the characteristics such as short reaction time, simple operation and highly yield, which provide significant information and basis for industrial production. |
| Key words: synthesis technology optimization cisatracurium besylate (+)-Di-1,4-toluoyl-D-tartaric acid |
