熊去氧胆酸小檗红碱酯的制备  

Preparation of ursodeoxycholic acid berberrubine ester

作　　者：龙硕 刘珍宝 彭东明[3] 刘晓钦 蒋婷 刘艳飞[1] LONG Shuo;LIU Zhenbao;PENG Dongming;LIU Xiaoqin;JIANG Ting;LIU Yanfei(School of Chemistry and Chemical Engineering,Central South University,Changsha 410083,China;Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China;School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]中南大学化学化工学院,湖南长沙410083 [2]中南大学湘雅药学院,湖南长沙410013 [3]湖南中医药大学药学院,湖南长沙410208

出　　处：《中南大学学报（自然科学版）》2020年第12期3389-3395,共7页Journal of Central South University:Science and Technology

基　　金：湖南省自然科学基金资助项目(2020JJ4680);湖南省教育厅科学重点研究项目(18A211);中南大学升华育英计划项目(CX20190242)。

摘　　要：采用桥连酯化法,对小檗碱进行熊去氧胆酸酯化修饰,合成新型化合物熊去氧胆酸小檗红碱酯,以提高小檗碱的降脂活性。首先以熊去氧胆酸为原料,1,2-二溴乙烷为桥连试剂,合成熊去氧胆酸-β-溴乙酯,再将其与小檗碱高温裂解后的产物小檗红碱反应,合成目标产物;探究反应温度、反应时间、投料比和反应溶剂等参数;对化合物进行核磁共振谱和质谱表征分析。研究结果表明:酯化反应最优条件是温度为25℃,以二甲基甲酰胺(DMF)为溶剂、K2CO3为缚酸剂;在醚化反应中,当温度为60℃,以DMF为溶剂、KI为催化剂时,收率最大,总收率达53.0%。To improve the lipid-lowering activity of berberine,a novel compounds berberrubine ursodeoxycholate was synthesized by bridged esterification method to modify the 9-O berberine with ursodeoxycholic acid.Firstly,ursodeoxycholic acid was used as the raw material and 1,2-dibromoethane was used as the bridging reagent to synthesize ursodeoxycholic acid-β-bromoethyl ester,and then it reacted with the high temperature pyrolytic product of berberine to synthesize the target product.The conditions such as temperature,time,feeding ratio and solvent were studied.The compound structure was confirmed by nuclear magnetic resonance(NMR)spectroscopy and mass spectrometry.The results show that the optimal conditions of the ester formation reaction are DMF used as solvent and K2CO3 as acid binding agent at 25℃.In the ether forming reaction,the yield is the highest when DMF is used as solvent and KI as catalyst at 60℃,and the total yield is 53.0%.

关 键 词：小檗红碱 熊去氧胆酸 酯化 亲核取代 

分 类 号：R914.4[医药卫生—药物化学]