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。
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.
作者
王亚静
柴奇
王可心
张龙
韩维娜
裴月湖
WANG Yajing;CHAI Qi;WANG Kexin;ZHANG Long;HAN Weina;PEI Yuehu(Shenyang Pharmaceutical University,Shenyang 110016,China;Harbin Medical University,Harbin 150081,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2020年第19期2344-2348,共5页
Chinese Journal of Modern Applied Pharmacy
基金
黑龙江省博士后科研启动基金(LBH-Q15111)。