新型烷氧基嘧啶拼接3-吡咯螺环氧化吲哚类化合物的合成及其抗肿瘤活性  

Synthesis and Antitumor Activities of Novel Pyrimidine-fused Spiropyrrolidine Oxindoles

作　　者：陈爽[1] 肖乐[2,3] 陈智勇[3] 杨超[3] 巩艺[3] 余章彪[3] 周英[3] 刘雄利[3] CHEN Shuang XIAO Le CHEN Zhi-yong YANG Chao GONG Yi YU Zhang-biao ZHOU Ying LIU Xiong-li(Institute of Biology and Engineering, Guizhou University of Medical Sciences, Guiyang 550025, China Chemical Group, Chenzhou City First Middle School, Chenzhou 423000, China Guizhou Engineering Center for Innovative Traditional Chinese Medicine and Ethnic Medicine, Guizhou University, Guiyang 550025, China)

机构地区：[1]贵州医科大学生物与工程学院,贵州贵阳550025 [2]郴州市第一中学化学组,湖南郴州423000 [3]贵州大学贵州省中药民族药创制工程中心,贵州贵阳550025

出　　处：《合成化学》2017年第1期14-17,25,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金地区基金资助项目(81560563);贵州省教学改革创新项目(SJJG201423);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);贵州省研究生教改课题(黔教研合JG字[2016]06)

摘　　要：以取代烷氧基嘧啶3-烯键氧化吲哚衍生物为原料,与肌氨酸及多聚甲醛在甲苯中回流经1,3-偶极子3+2环加成反应,合成了8个新型烷氧基嘧啶拼接3-吡咯螺环氧化吲哚类化合物(3a^3h),产率67%~82%,d/r值6/1~20/1,其结构经~1H NMR,^(13)C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了3a^3h对人肺癌细胞(A549)、人前列腺癌细胞(PC-3)和人白血病细胞(K562)的体外抗肿瘤活性。结果表明:3d和3g对人白血病细胞K562具有明显的活性,IC50分别为24.1 mol·L^(-1)和32.4μmol·L^(-1),接近阳性对照药顺铂。Eight novel pyrimidine-fused spiropyrrolidine oxindoles（3a-3h） were synthesized by 1,3-dipolar reaction of pyrimidine-fused 3-alkenyloxindoles with azomethine ylides（thermally generated in situ from sarcosine and formaldehyde）.The yields and d/r of 3a-3h were 67%-82% and 6/1-20/1,respectively.The structures were characterized by ^1H NMR,^13C NMR and HR-MS（ESI-TOF）.The in vitro antitumor activities against human lung cancer cells（A549）,human prostate cancer cells PC-3 and human leukemia cells（K562） were demonstrated by MTT assays.The results showed that 3d and 3g exhibited certain in vitro inhibitory activities against K562 with IC50 of 24.1 mol·L^-1 and 32.4mol·L^-1,respectively,equipotent to the positive control of Cisplatin.

关 键 词：肌氨酸 甲醛 烷氧基嘧啶3-烯键氧化吲哚 烷氧基嘧啶拼接3-吡咯螺环氧化吲哚 1 3-偶极环加成反应 合成 抗肿瘤活性 

分 类 号：O626.13[理学—有机化学] O623.7[理学—化学]