新型六氢吡啶-2,3-并吲哚化合物的合成及其抗肿瘤活性  

Synthesis and Anti-tumor Activities of Novel Hexahydro-1H-pyrido[2,3-b]indole Compounds

作　　者：张文会[1] 王丹丹[1] 刘欢欢[1] 巩艺[1] 刘雄利[1] 陈智勇[1] 周英[1] 李午戊[2] 

机构地区：[1]贵州大学药学院贵州省中药民族药创制工程中心,贵州贵阳550025 [2]咸阳师范学院化学与化工学院,陕西咸阳712000

出　　处：《合成化学》2016年第5期380-383,388,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金青年基金资助项目(21302024);国家自然科学地区基金资助项目(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];咸阳师范学院专项科研基金资助项目(10XSYK311)

摘　　要：以3-取代氧化吲哚与丙烯酸酯为原料,经Michael加成反应制得中间体——3-丙酸酯取代氧化吲哚(3a^3d);3a^3d与甲胺发生酰胺化反应制得3-丙酰胺取代氧化吲哚(4a^4d);4a^4d用氢化铝锂还原-环化,合成了4个六氢吡啶-2,3-并吲哚化合物(5a^5d);5a和5b用氢化铝锂还原合成了2个六氢吡啶-2,3-并吲哚化合物(6a和6b),5a^5d,6a和6b均为新化合物,总产率42%~61%,其结构经~1H NMR,^(13)C NMR和HR-ESIMS表征。采用MTT法研究了5a^5d,6a和6b对人肺癌细胞(A549),人前列腺(PC-3)和人白血病细胞(K562)的体外抗肿瘤活性。结果表明:5b对A549,PC-3和K562的抑制活性均较好,其IC50分别为27.2μmol·L^(-1),37.5μmol·L^(-1)和21.7μmol·L^(-1)。Four intermediates,3-propionate oxindole（ 3a ~ 3d）,were obtained by Michael addition,using 3-substituted oxindoles and acrylates as starting materials. 3-Propionamide oxindoles（ 4a ~ 4d）were prepared by the reaction of 3a ~ 3d with methylamine. Four novel hexahydro-1H-pyrido[2,3-b]indole compounds（ 5a ~ 5d） were synthesized by reductive-cyclization from 4a ~ 4d,using Li Al H4 as reductant. Two novel hexahydro-1H-pyrido[2,3-b]indole compounds（ 6a and 6d） were synthesized by reduction of 5a and 5b with Li Al H4. The overall yield of 5a ~ 5d,6a and 6b were 42% ~ 61%. The structures were characterized by^1 H NMR,^（13） C NMR and HR-ESI-MS. The in vitro anti-tumor activities of 5 and 6 against human prostate cancer cells（ PC-3）,human lung cancer cells（ A549） and human leukemia cells（ K562） were investgated by MTT method. The results demonstrated that 5b exhibited better inhibition activity against K562,A549 and PC-3. IC50 were 27. 2 μmol·L^（-1）,37. 5 μmol·L^（-1）and 21. 7 μmol·L^（-1）,respectively.

关 键 词：3-取代氧化吲哚 六氢吡啶-2 3-并吲哚化合物 MICHAEL加成反应 酰胺化反应 还原-环化反应 合成 抗肿瘤活性 

分 类 号：O625.6[理学—有机化学] O626.1[理学—化学]