雌三醇合成新工艺研究  

Study on New Synthesis Technology of Estriol

作　　者：罗剑 邹辉[1] 李岩 姚倩 夏志强 杨小红[1] 杜乐 LUO Jian;ZOU Hui;LI Yan;YAO Qian;XIA Zhiqiang;YANG Xiaohong;DU Le(Medical School,Hunan Normal University,Changsha 410000,China;Changsha Jingyi Medical Technology Co.,Ltd.,Changsha 410000,China;Ordos Central Hospital,Ordos 017000,China)

机构地区：[1]湖南师范大学医学院,湖南长沙410000 [2]长沙晶易医药科技股份有限公司,湖南长沙410000 [3]鄂尔多斯市中心医院,内蒙古自治区鄂尔多斯017000

出　　处：《合成化学》2025年第2期111-118,共8页Chinese Journal of Synthetic Chemistry

基　　金：湖南省自然科学基金资助项目(2021JJ30466)。

摘　　要：开发一种新的雌三醇合成工艺,易于实现工业化生产。以雌酚酮为起始原料,通过乙酰化反应、环氧化反应、水解反应和还原反应得到雌三醇,其结构经LC/MS、^(1)H NMR、^(13)C NMR和旋光度进行确证,总收率达47.32%;HPLC液相纯度达到99.7%以上,且单杂纯度均小于0.10%,满足原料药质量标准。该工艺路线较传统路线最大的优势在于使用自制单过氧邻苯二甲酸氧化剂,可大幅降低雌三醇原料药生产成本,大幅缩短反应时间,极大地缩短生产周期,降低生产能耗。此外,由于单过氧邻苯二甲酸爆炸限较间氯过氧苯甲酸低,安全性高,较一般的过酸氧化剂水溶性好,更容易去除。雌三醇的新合成工艺简单安全,试剂绿色环保,易实现工业化生产。Develop a new synthesis process for estriol,which is easy to achieve industrial production.Estriol was obtained from estrone as the starting material through acetylation,epoxidation,hydrolysis,and reduction reactions.Its structure was confirmed by LC/MS(Liquid chromatography-mass spectrometry),^(1)H NMR,^(13)C NMR,and optical rotation,with a total yield of 47.32%.The HPLC liquid phase purity reaches over 99.7%,and the single impurity purity is less than 0.10%,meeting the quality standards of the raw materials.The biggest advantage of this process route compared to traditional routes is the use of self-made peroxyphthalic acid oxidants,which can significantly reduce the production cost of estriol raw materials,shorten reaction time,greatly shorten production cycle,and reduce production energy consumption.In addition,due to the lower explosion limit and higher safety of mono peroxyphthalic acid compared to meta chloroperoxybenzoic acid,it has better water solubility and is easier to remove than general peroxy oxidants.The new synthesis process of estriol is simple and safe,the reagent is green and environmentally friendly,and it is easy to achieve industrial production.

关 键 词：雌三醇 雌激素 单过氧邻苯二甲酸 环氧化反应 成本优势 工业化生产 

分 类 号：TQ467.92[化学工程—制药化工]