马兜铃酸Ⅰ-脱氧核苷结合物对照品制备方法研究  

Study on preparation method of reference substance of aristolactam Ⅰ-deoxyriboside adducts

作　　者：杨晓芹 屈碧琼 刘洁[1,3] 胡信全 肖红斌[1,3] YANG Xiao-qin;QU Bi-qiong;LIU Jie;HU Xin-quan;XIAO Hong-bin(Research Center of Chinese Medicine Analysis and Transformation,Beijing University of Chinese Medicine,Beijing 100029,China;School of Chinese Materia Medical,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;College of Chemical Engineering,Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]北京中医药大学中药分析与转化研究中心,北京100029 [2]北京中医药大学中药学院,北京100029 [3]北京中医药大学北京中医药研究院,北京102488 [4]浙江工业大学化学工程学院,浙江杭州310014

出　　处：《中国中药杂志》2024年第10期2728-2733,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82173957);国家“重大新药创制”科技重大专项(2018ZX09101-002)。

摘　　要：建立了以马兜铃内酰胺Ⅰ为原料的溴化及交叉偶联二步有机合成工艺,粗产物经过4种溶剂除杂纯化,制得马兜铃酸Ⅰ(aristolochic acidsⅠ,AAⅠ)的3种脱氧核苷结合物产物AAⅠ-dA、AAⅠ-dG、AAⅠ-dC,2步反应的收率均可达到90%,产物纯度均大于98%,满足中药化学对照品定性定量要求。该工艺重复性好,适合放大制备,具有制备步骤短及纯化操作高效、勿需色谱分离、产品收率及纯度高等特点。相比其他方法,该方法优势显著,更适于马兜铃酸Ⅰ-脱氧核苷结合物化学对照品制备。新开发的工艺为马兜铃酸Ⅰ-脱氧核苷结合物对照品的制备提供了技术支撑,为相关毒理学研究提供了坚实的物质基础。A two-step synthetic process of bromination and cross-coupling with aristololactam Ⅰ as raw material was successfully developed.Three aristolactam Ⅰ-deoxyriboside adducts,namely AAⅠ-dA,AAⅠ-dG,and AAⅠ-dC were obtained after a sequential procedure of impurity removal and purification in four different solvents.The yield of the two-step reaction can reach 90%,and the purity of the product is more than 98%,which can meet the requirements of qualitative and quantitative analyses as traditional Chinese medicine chemical reference products.The process has been proven to have good repeatability and scalability,and it features a concise preparation procedure,efficient purification,and high yield and purity,requiring no chromatographic separation.Compared with pre-vious methods,the newly developed process has significant advantages and is suitable for the preparation of chemical reference products of aristolactam Ⅰ-deoxyriboside adducts.This process provides technical support for the preparation of reference products of aristolactam Ⅰ-deoxyriboside adducts and a solid material basis for the related toxicological research.

关 键 词：马兜铃酸Ⅰ-脱氧核苷结合物 合成制备 溴代反应 偶联反应 

分 类 号：R284[医药卫生—中药学]