文献类型：期刊文献

中文题名：基于莪术醇胺氟化结构修饰的三维天然产物片段库的构建

英文题名：Aminofluorination-Based Structural Modification of Curcumol for the Construction of 3D-Shaped Natural Product Fragment Library

作者：李响[1,2];张依凡[1];陆凯琳[2];刘石惠[1];张永强[2]

机构：[1]嘉兴学院医学院,浙江嘉兴314001;[2]华东理工大学药学院,上海200237

年份：2022

卷号：42

期号：7

起止页码：2124

中文期刊名：有机化学

外文期刊名：Chinese Journal of Organic Chemistry

收录：CSTPCD;;Scopus;WOS:【SCI-EXPANDED(收录号:WOS:000853272500018)】；北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：Project supported by the National Natural Science Foundation of China (Nos. 22001096, 21871086), the Natural Science Foundation of Zhejiang Province (No. LQ21B020008), the Start Up Funds of Jiaxing University (No. CD70519040) and the Jiaxing University "Hundred Youth" Training Talents (No. CD70621018).

语种：中文

中文关键词：莪术醇;结构修饰;胺氟化;三维片段;基于片段的药物发现

外文关键词：curcumol;structural modification;aminofluorination;3D-shaped fragments;fragment based drug discovery

摘要：富含sp^(3)中心的三维天然产物结构由于其独特的生物活性,在药物化学及生物化学方面越来越受到重视.以天然产物莪术醇为基础,通过光催化的胺氟化反应,高效引入胺和氟两个潜在的结合或反应位点,构建了以三维形状天然产物为核心的片段库.通过这一策略,合成了包含24个新型莪术醇衍生物的片段库,进一步计算结果表明,所获得的片段库具有高三维度、天然产物相似性和优质的片段属性,在基于片段的药物发现中开辟了一个新的化学空间.
The biological significance of sp^(3)-rich synthetic scaffolds with natural product like features yet distinct global frameworks is being increasingly recognized in medicinal chemistry and biochemistry.Herein,a fragment library consisting of 3D-shaped natural product fragments was assembled.Library construction was performed by photocatalytic amidofluorination of curcumol to incorporate amine and fluorine as potential binding groups and synthetic growth points.Through this strategy,a fragment library of 24 fragments was generated,which was demonstrate to have high three-dimensionality,natural product likeness and superior fragment-like properties,covering a novel chemical space in fragment based drug discovery.