系列C3α-位芳基取代的四氢吡咯并吲哚骨架衍生物的合成  

Synthesis of Alkaloid Derivatives with Pyrroloindoline Skeleton Substituted on C3α-with Different Types of Arenes

作　　者：孔晨[1] 王雨[1] 王霞[2] 王琼[2] 宋颢[1] 

机构地区：[1]四川大学华西药学院靶向药物与释药系统教育部重点实验室,成都610041 [2]四川大学华西第二医院西部妇幼研究院分子与转化医学实验室,成都610041

出　　处：《高等学校化学学报》2013年第4期846-852,共7页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21002066)资助

摘　　要：通过银促进的傅-克反应可以合成系列C3α-位为不同类型芳基取代的四氢吡咯并吲哚骨架的类天然产物.在该合成方法的基础上,发现C3α-位分别为对乙酰氨基苯基取代和甲基吲哚取代的四氢吡咯并吲哚类衍生物3a和3b对多种肿瘤细胞均表现出微摩尔级的活性,是具有重要临床应用前景的药物候选化合物.为了进一步研究该类化合物的成药性及其构效关系,以化合物3a为前体化合物合成了一系列类天然产物(化合物4～17),对其抗肿瘤活性进行了研究,并初步探讨了其构效关系.所合成化合物的结构经1H NMR、13C NMR和HRMS分析确证.本研究为该类化合物的临床前研究奠定了基础.Alkaloids bearing a pyrroloindoline skeleton substitutedon C3a- with different types of arenes form a major class of indole alkaloids which draw attention to synthetic chemists due to their broad range of potent biological activities. The derivatives 3a and 3b were obtained via a silver-promoted Friedel-Crafts reaction. Based on this method, derivatives 3a and 3b were found exhibiting micro-molar level activity against a variety of tumor cell, which are potential drug candidate. In order to study the drug-ability and structure-activity relationships（SARs） of these compounds, a series of natural product-like library analogues（4--17） was syn- thesized and the SARs of these compounds were studied. The structures of the compounds were confirmed by 1H NMR, 13 C NMR and HRMS. The research lays the foundation for pre-clinical studies of these compounds.

关 键 词：四氢吡咯并吲哚生物碱 衍生物 抗肿瘤 构效关系 

分 类 号：O629.31[理学—有机化学]