基于官能化反应合成喹唑啉衍生物研究.pdfVIP

摘要 喹唑啉骨架广泛存在于各种生物碱和具有生物药理活性的有机分子中，开始 应用于抗疟原虫领域、抗菌领域。近几十年来，靶向治疗药物越来越受欢迎,个 别喹唑啉衍生物成为靶向药物用于抗肿瘤，正是因为其优越的骨架和生物活性， 成为研究的目标。将喹唑啉进行官能团修饰，引入不同取代基和其它骨架，对喹 唑啉衍生物库扩充，为后续生物活性物质筛选做了铺垫。 另外一方面1,3-偶极的活泼性和喹唑啉类化合物含氮导向基团，可以进行高 立体选择性环加成，也可以通过C-H 活化在2-芳基上引入不同基团，比如卤素， 烷基，烷氧基等。本论文主要以喹唑啉-3-氧化物、2-芳基喹唑啉酮为原料，通过 1,3-偶极的[3+2]环加成或金属催化偶联等，实现了对喹唑啉和喹唑啉酮扩环（五 元杂环和七元杂环）、在喹唑啉 C4 位引入叠氮，构建一系列未有的喹唑啉衍生 物结构。研究的内容具体分为以下三部分： （1）以喹唑啉-3-氧化物和 3- 甲氧基丙烯酸甲酯为原料，通过 1,3-偶极的 [3+2]环加成合成异噁唑并[2,3-c]喹唑啉。反应不需要催化剂、温度适中，具有高 效的立体选择性。 （2 ）以 2-邻溴芳基喹唑啉和邻溴苯酚为原料，在亚铜催化作用下，串联 C-O(S)/C-N 有效合成二苯并氧氮杂卓喹唑啉酮。反应底物适应性良好，收率高。 （3 ）以2-芳基喹唑啉酮为原料，叠氮化钠作为叠氮试剂，发展了合成4-叠 氮喹唑啉反应。可以以温和的条件进行，得到一系列含有叠氮的喹唑啉衍生物。 关键词：喹唑啉衍生物；官能化；3- 甲氧基丙烯酸甲酯；叠氮化钠 I Abstract The quinazoline skeleton is widely present in various alkaloids and organic molecules with biopharmacological activity. It has been used in the field of anti-malarial parasites and antibacterial. In recent decades, targeted therapeutic drugs have become more and more popular. Individual quinazoline derivatives have become targeted drugs for anti-tumor. It is precisely because of their superior backbone and biological activity that they have become the research target . The functional groups of quinazoline were modified, different substituents and other skeletons were introduced, and the quinazoline derivative library was expanded to pave the way for subsequent screening of biologically active substances. On the other hand, the 1,3-dipolar active and quinazoline compounds have nitrogen-directed groups, which can carry out high stereoselective cycloaddition, and can also introduce different groups on the 2-aryl group through C-H activation. For example, halogen, alkyl, alkoxy and the like. In this th