新型异噁唑-三氟甲基螺环氧化吲哚类化合物的合成及其抗白血病活性  

Synthesis and Anti-human Leukemia Cells Activities of Trifluoromethyl Containing Isoxazole-based Oxindoles

作　　者：潘博文 韩晓雪 石洋 田又平 刘雄利[2] PAN Bo-wen;HAN Xiao-xue;SHI Yang;TIAN You-ping;LIU Xiong-li(School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China;National & Local Joint Engineering Research Center for the Exploition of Homology Resources of Medicine and Food, Guizhou University, Guiyang 550025, China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]贵州大学西南药食两用资源开发利用技术国家地方联合工程研究中心,贵州贵阳550025

出　　处：《合成化学》2021年第12期1026-1032,共7页Chinese Journal of Synthetic Chemistry

基　　金：黔科合基础项目(ZK[2021]560)。

摘　　要：以硝基异噁唑苯乙烯与靛红衍生的三氟甲基亚胺为原料,在有机碱三乙胺的催化作用下,发生Michael加成环化反应,得到了12个未见文献报道的异噁唑-三氟甲基螺环氧化吲哚类化合物3a~3l,产率73%~89%,dr值10/1~>20/1,其结构经^(1)H NMR,^(13)C NMR和HR-MS(ESI-TOF)表征,通过单晶进一步进行了确定化合物3e的相对构型。该类化合物含有连续4个立体中心,其中包含一个螺环季碳中心。采用MTT法研究了3a~3l对人白血病细胞(K562)的体外抗肿瘤活性。结果表明:化合物3c,3d,3h和3i对K562具有一定的抑制活性,说明异噁唑-三氟甲基螺环氧化吲哚骨架可以作为抗肿瘤先导化合物进一步研究。In this paper,we report a Michael addition cyclization reaction of styrylisoxazoles and N-2,2,2-trifluoroethylisatin ketimines in the presence of the catalyst Et_(3)N.The process enables synthesis of 12 new trifluoromethyl containing isoxazole-based oxindoles bearing four contiguous stereogenic centers including one tetra substituted carbon,with high efficiency(75%~89%yields and 10/1~>20/1 diastereomeric ratio).The structures of products 3 were characterized by ^(1)H NMR,^(13)C NMR and HR-MS(ESI-TOF).The relative configuration of compound 3e was further determined by the single crystal.The in vitro antitumor activities against human leukemia cells(K562)were demonstrated by MTT assays using the commercially available broad-spectrum anticancer drug Cisplatin as a positive control.The results showed that compounds 3c,3d,3h and 3i showed good cytotoxic effects,which suggested that trifluoromethyl containing isoxazole-based oxindole hybrids may be potential leads for further biological screenings.

关 键 词：硝基异噁唑苯乙烯 三氟甲基亚胺 MICHAEL加成反应 螺环季碳中心 氧化吲哚 合成 活性 

分 类 号：O626.13[理学—有机化学] O623.7[理学—化学]