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
杨晓芹 1屈碧琼 1刘洁 2胡信全 3肖红斌2
作者信息
- 1. 北京中医药大学 中药分析与转化研究中心,北京 100029;北京中医药大学 中药学院,北京 102488
- 2. 北京中医药大学 中药分析与转化研究中心,北京 100029;北京中医药大学 北京中医药研究院,北京 100029
- 3. 浙江工业大学 化学工程学院,浙江 杭州 310014
- 折叠
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 acids Ⅰ,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.
Abstract
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 pu-rity 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 aristolac-tam 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Key words
aristolactam Ⅰ-deoxyriboside adducts/synthesis and preparation/bromination reaction/coupling reaction引用本文复制引用
基金项目
国家自然科学基金(82173957)
"重大新药创制"科技重大专项(2018ZX09101-002)
出版年
2024
NETL
NSTL
万方数据