嘧啶拼接3-烯键氧化吲哚衍生物的合成及其抗肿瘤活性  

Synthesis and Antitumor Activities of Pyrimidine-fused 3-Alkenyloxindoles

作　　者：周根[1] 刘欢欢[1] 王丹丹[1] 韩朔楠 杨超[1] 林冰[1] 刘雄利[1] 赵致[1] 周英[1] ZHOU Gen LIU Huan-huan WANG Dan-dan HAN Shuo-nan YANG Chao LIN Bing LIU Xiong-li ZHAO Zhi ZHOU Ying(Guizhou Medicine Edicine Edible Plant Resources Research and Developmant Center, Guizhou University, Guiyang 550025, Chin)

机构地区：[1]贵州大学贵州省药食同源植物资源开发工程技术研究中心,贵州贵阳550025

出　　处：《合成化学》2017年第3期185-189,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(81560563;81660576;81603390);贵州省教学改革创新项目(SJJG201423;黔教研合JG字[2016]06);贵州省制药工程专业学位研究生工作站(黔教研合JYSZ字【2014】002);贵州省科技合作计划项目(黔科合LH字(2015)7666号)

摘　　要：以2-吲哚酮与3,5-二氯嘧啶甲醛为原料,经Knoevenagel加成消除反应和取代反应合成了11个新型的嘧啶拼接3-烯键氧化吲哚衍生物(3a^3k),产率70%~91%,Z/E值15∶1~>20∶1,其结构经1H NMR,13C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了3a^3k对人肺癌细胞(A549)和人白血病细胞(K562)的体外抗肿瘤活性。结果表明:3a,3c,3f,3g和3j对K562具有较好的抑制活性(IC50分别为29.3,27.6,28.5,24.0和27.0μmol·L^(-1)),3a,3h和3j对A549具有较好的抑制活性(IC50分别为28.1,16.4和25.2μmol·L^(-1))。Eleven novel pyrimidine-fused 3-alkenyloxindoles（3a - 3k） were synthesized via a Knoevenagel condensation/substitution reaction of pyrimidine aldehydes with 2-oxindoles. The yields and Z/E of 3a - 3k were 65% - 87% and 5 ∶ 1 - 20 ∶ 1,respectively. The structures were characterized by1 H NMR,13 C NMR and HR-MS（ESI-TOF）. The in vitro antitumor activities against human lung cancer cells（A549） and human leukemia cells（K562） were demonstrated by MTT assays. The results showed that 3a,3c,3f,3g and 3j exhibited good inhibition activities against K562 with IC50 of 29. 3,27. 6,28. 5,24. 0,27. 0 μmol·L^-1,respectively. 3a,3h and 3j exhibited good inhibition acitvities against A549,showing IC50 of 28. 1,16. 4,25. 2 μmol·L^-1,respectively.

关 键 词：2-吲哚酮 嘧啶甲醛 KNOEVENAGEL反应 嘧啶拼接3-烯键氧化吲哚 抗肿瘤活性 合成 

分 类 号：O626.13[理学—有机化学] O623.7[理学—化学]