18α-甘草次酸的微波辅助合成及工艺优化  

Microwave-assisted synthesis and process optimization of 18α-glycyrrhetinic acid

作　　者：戚蕊 薛康 褚福浩[1] 苏进[1] 孙宇菲 伊冰清 赵国栋 雷海民[1] QI Rui;XUE Kang;CHU Fu-hao;SU Jin;SUN Yu-fei;YI Bing-qing;ZHAO Guo-dong;LEI Hai-min(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中南药学》2023年第7期1769-1774,共6页Central South Pharmacy

基　　金：“北京市科技新星”人才项目(No.Z211100002121128);国家自然科学基金资助项目(No.82274082)。

摘　　要：目的将微波合成技术应用于高附加值中药单体18α-甘草次酸的制备,以建立更高效、经济的工艺路线。方法以天然来源丰富且廉价的18β-甘草次酸为原料,通过微波辐射促进C-18β的构型翻转,实现18α-甘草次酸的制备,利用HRMS、^(1)H-NMR、^(13)C-NMR、HPLC、旋光和熔点进行结构确认及纯度鉴定;首次实现双键移位副产物的分离并通过X-单晶衍射确认结构,辅助推测反应机制使过程更清晰。结果相比于传统加热,微波辅助技术极大提高了制备效率,以5.0 g反应原料为例,反应温度120℃,反应时间20 min;简化了后处理操作,重结晶溶剂200 mL,回流时间30 min。结论微波辅助合成法是目前18α-甘草次酸高效、经济的制备方法,符合绿色化学的理念;双键移位副产物的首次分离和结构鉴定,弥补了相关研究的空白,为后续质量控制奠定了基础。Objective To develop an economic and efficient route for 18α-glycyrrhetinic acid synthesis with the assistance of microwave,a high-value traditional Chinese medicine monomer.Methods Cheap and numerous 18β-glycyrrhetinic acid was used as the starting material.Microwave irradiation helped accelerate the stereocenter inversion of C-18βto furnish 18α-glycyrrhetinic acid with the confirmation of HRMS,^(1)H-NMR,^(13)C-NMR,HPLC,optical rotation and melting point.Notably,side-products with double-bond migration were isolated and characterized by X-ray diffraction for the first time,which facilitated the mechanism analysis.Results Compared to the conventional heating protocol,the efficiency was significantly improved,taking 5.0 g of reaction raw materials as an example,the reaction temperature reached 120℃and the reaction time was 20 min,post work procedure simplified,the recrystallization solvent was 200 mL,and the reflux time was 30 min.Conclusion Microwave-assisted 18α-glycyrrhetinic acid synthesis is now the most efficient and economic protocol for currently,which is in accordance with the principle of green chemistry.Furthermore,first characterization of side-products has filled the previous research gap,laying foundation for futher quality control.

关 键 词：18Β-甘草次酸 18α-甘草次酸 微波辅助合成 双键移位副产物 

分 类 号：R914[医药卫生—药物化学] R283[医药卫生—药学]