异长叶烷基-喹唑啉-2-胺衍生物的合成与生物活性评价  

Synthesis and Biological Evaluation of Isolongifolanylquinazolin-2-amine Derivatives

作　　者：杨金来[1,2] 芮坚 吴陈亮 杨丽娟[2] 杨益琴[3,4] 徐徐 谷文[3,2] 王石发[3,2] YANG Jin-lai;RUI Jian;WU Chen-liang;YANG Li-juan;YANG Yi-qin;XU Xu;GU Wen;WANG Shi-fa(Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing ForestryUniversity, Nanjing 210037, Jiangsu, China;Key Laboratory of High Efficient Processing of Bamboo of ZhejiangProvince, China National Bamboo Research Center, Hangzhou 310012, Zhejiang, China;College of Light Industryand Food Engineering, Nanjing Forestry University, Nanjing 210037, Jiangsu, China;College of ChemicalEngineering, Nanjing Forestry University, Nanjing 210037, Jiangsu, China)

机构地区：[1]国家林业局竹子研究开发中心浙江省竹子高效加工重点实验室,浙江杭州310012 [2]南京林业大学化学工程学院,江苏南京210037 [3]南京林业大学林业资源高效加工利用协同创新中心,江苏南京210037 [4]南京林业大学轻工与食品学院,江苏南京210037

出　　处：《精细化工》2019年第2期277-282,共6页Fine Chemicals

基　　金：国家自然科学基金(31470592)~~

摘　　要：以异长叶烷酮为原料,经缩合、环化等反应合成出6个喹唑啉-2-胺衍生物(Ⅲa～Ⅲf)。采用1HNMR、13CNMR、IR、HRMS等对其结构进行了表征。采用MTT法考察了化合物Ⅲa～Ⅲf对人肝癌细胞(Hep G2)和人脐静脉内皮细胞(HUVECs)的抑制活性。结果表明:化合物Ⅲa、Ⅲb、Ⅲd、Ⅲf[半抑制浓度(IC50)分别为8.58±0.5、44.52±0.9、57.18±0.8、32.83±0.6μmol/L]对Hep G2有一定的抗肿瘤活性。其中,4-(4?-氯苯基)-6,6,10,10-四甲基-5,6,6a,7,8,9,10,10a-八氢-6a,9-甲基苯并[h]喹唑啉-2-胺(Ⅲa)抗HepG2的活性最强;只有4-[4?–(二甲基氨基)苯基]-6,6,10,10-四甲基-5,6,6a,7,8,9,10,10a-八氢-6a,9-甲基苯并[h]喹唑啉-2-胺(Ⅲf)对HUVECs有抑制活性。同时,采用叶浸渍法考察了化合物Ⅲa～Ⅲf对桃蚜的杀虫活性,结果表明,化合物Ⅲa、Ⅲd[致死中浓度(LC50)=41.0073,37.4589 mg/L]对桃蚜具有较好的杀虫活性。A series of quinazolin-2-amine derivatives(Ⅲa~Ⅲf) were synthesized by condensation, cyclization and so on from isolongifolanone and characterized by ^1HNMR,^13CNMR, IR and HRMS. Their inhibitory activity against human hepatoma cell(HepG2) and human umbilical vein endothelial cells(HUVECs) were evaluated by MTT assay. The results showed that the half maximal inhibitory concentrations of compounds Ⅲa,Ⅲb,Ⅲd and Ⅲf were 8.58±0.5, 44.52±0.9, 57.18±0.8 and 32.83±0.6 μmol/L, indicating that these compounds showed moderate antitumor activity against HepG2. Among these compounds, compound Ⅲa, 4-(4'-chlorophenyl)-6,6,10,10-tetramethyl-5,6,6a,7,8,9,10,10a-octahydro-6a, 9-methanobenzo[h]quinazolin-2-amine, had the best activity against HepG2. Only 4-(4’-(N,N-dimethylamino) phenyl)-6,6,10,10-tetramethyl-5,6,6a,7,8,9,10,10a-octahydro-6a,9-methanobenzo[h]quinazolin-2-amine(Ⅲf) showed a certain inhibitory activity against HUVECs. These compounds were also carried out to evaluate against Myzus persicae by a leaf-dipping method. It was found that compounds Ⅲa and Ⅲd gave excellent insecticidal activity against myzus persicae with corresponding lethal concentration(LC50) of 41.0073 and 37.4589 mg/L.

关 键 词：异长叶烷酮 喹唑啉-2-胺衍生物 抗肿瘤活性 杀虫活性 医药原料 

分 类 号：TQ254[化学工程—有机化工]