造影剂碘普罗胺的合成工艺改进  

Improved synthesis of contrast agent iopromide

作　　者：温涛 欧儒鹏 王新仙 卢定强[2] WEN Tao;OU Rupeng;WANG Xinxian;LU Dingqiang(College of Biotechnology and Pharmaceutical Engineering,Nanjing Tech University,Nanjing 211800,China;College of Pharmaceutical Science,Nanjing Tech University,Nanjing 211800,China;Jiangsu Provincial Institute of Materia Medica Co.,Ltd.,Nanjing 211800,China)

机构地区：[1]南京工业大学生物与制药工程学院,江苏南京211800 [2]南京工业大学药学院,江苏南京211800 [3]江苏省药物研究所,江苏南京211800

出　　处：《生物加工过程》2023年第3期280-285,共6页Chinese Journal of Bioprocess Engineering

摘　　要：碘普罗胺是一种常用的碘造影剂。以3—氨基—5—[[(2,3—二羟基丙基)氨基]羰基]苯甲酸为起始原料,通过6步反应合成常用的碘化造影剂碘普罗胺。将S 1碘化后,将所得的三酰中间体M 1进行O Ac保护,随后进行酰胺化,生成2甲氧基乙酰基。然后通过酸性氯化物中间体M 4实现第二次酰胺化。最后,使用NaOH水溶液将两个乙酰保护基团水解断裂。再经过大孔吸附树脂和阴阳离子树脂对反应液进行一次纯化,得到碘普罗胺粗品,然后在乙醇溶剂中重结晶进一步纯化。该方法6步反应的总收率为25.6%。同时合成产物经核磁共振氢谱(1 H NMR)结构确证。该合成工艺简单易操作,适合应用于工业化生产。该合成工艺简单、易操作,不使用昂贵原料,适合应用于工业化生产。A modified synthesis of iopromide,a commonly used iodinated contrast agent,was accomplished in six steps starting from cheap 3-amino-5-[[(2,3-dihydroxypropyl)amino]carbonyl]benzoic acid.Upon iodination of S-1,the resulting triiodo intermediate M-1 was subjected to O-Ac protection and subsequent amidation to introduce 2-methoxy acetyl group.The second amidation was then achieved through an acid chloride intermediate M-4.Finally,the two acetyl protection groups were cleaved by hydrolysis with aqueous NaOH.The crude iopromide,which was obtained upon treatment with macroporous adsorption resin and anioncation resin,was further purified by recrystallization in ethanol solvent.The overall yield of this six-step sequence was 25.6%,and the final product was confirmed by 1H-NMR.This synthesis process proved to be straightforward,easy to operate,and suitable for industrial production.

关 键 词：碘普罗胺 碘代 合成 工艺改进 

分 类 号：R914.5[医药卫生—药物化学]