Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (4): 1017-1027.DOI: 10.6023/cjoc201909026 Previous Articles     Next Articles


苑睿a, 崔浩b, 陈雯b, 任璇璇b, 周杭b, 徐慧b, 孙雅文b, 梁燕妮b, 宛瑜a, 刘金娟a, 吴翚a,b   

  1. a 江苏师范大学省药用植物生物技术重点实验室 江苏徐州 221116;
    b 江苏师范大学化学与材料科学学院 江苏徐州 221116
  • 收稿日期:2019-09-17 修回日期:2019-11-06 发布日期:2020-05-06
  • 通讯作者: 吴翚, 宛瑜, 刘金娟;;
  • 基金资助:

Synthesis of 1,7-Bis(N-substituted-aminomethyl)-2,8-dihydroxy-Tröger's Bases and Their Application in Aldol-Ullmann Reaction

Yuan Ruia, Cui Haob, Chen Wenb, Ren Xuanxuanb, Zhou Hangb, Xu Huib, Sun Yawenb, Liang Yannib, Wan Yua, Liu Jinjuana, Wu Huia,b   

  1. a Key Laboratory of Biotechnology for Medicinal Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou, Jiangsu 221116;
    b School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, Jiangsu 221116
  • Received:2019-09-17 Revised:2019-11-06 Published:2020-05-06
  • Supported by:
    Project supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Natural Science Research Projects in Universities of Jiangsu Province (No. 19KJB430019), the Science and Technology Foundation of Xuzhou City (No. KC19242), the Aid Project for PhD Faculties in Jiangsu Normal University (No. 17XLR023) and the Graduate Student Scientific Research Innovation Projects in Jiangsu Province (Nos. KYCX18_2111, KYCX18_2116).

1,7-Bis(N-substituted-aminomethyl)-2,8-dihydroxy-Tröger's bases (4) were synthesized and used as efficient organocatalyst for the Aldol reaction of 4-hydroxylcoumarin and 2-benzylidenemalononitrile (or methyl(ethyl)-2-cyano-3-phenylacrylate) to afford 2-amino-4-aryl-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitriles (carboxylates) (8). Subse-quently, they were used as the efficient ligand to promote the Pd-catalyzed Aldol-Ullmann reaction to give 7-aryl-7,12-dihydro-6H-chromeno[3',4':5,6]pyrano[2,3-b]indol-6-one (10) and 5'(or 5',7')-substituted-6H,12H-spiro[chromeno[3',4':5,6]-pyrano[2,3-b]indole-7,3'-indoline]-2',6-dione (12), respectively. The anti-cancer activity on human three positive breast cancer cells (MCF-7), human three negative breast cancer cells (MDA-MB-231), human hepatoma cells (HepG2), human hepatoma cells (MHCC-97H) and cytotoxicity on human hepatocyte cells (LO2) of catalyst 4 and all products in vitro were evaluated. 1,7-Bis((methylamino)methyl)-6H,12H-5,11-methanodibenzo[b,f] [1,5]diazocine-2,8-diol (4b) had selective inhibition (inhi-bition rate>30%) on MCF-7 cells while 1,7-bis(((1-phenylethyl)amino)methyl)-6H,12H-5,11-methanodibenzo[b,f] [1,5]diazo-cine-2,8-diol (4d) and 1,7-bis(((pyridin-2-ylmethyl)amino)methyl)-6H,12H-5,11-methanodibenzo[b,f] [1,5]diazocine-2,8-diol (4e) had selective inhibition on MDA-MB-231 cells. 2-Amino-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-dihydropyrano[3,2-c]chromene-3-carbonitrile (8q) had strong inhibitory effects on three kinds of cancer cells except MDA-MB-231 while 2-amino-4-(4-bromophenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (8a), 2-amino-4-(2,4-dichlorophenyl)-5-oxo-4H,5H-dihydropyrano[3,2-c]chromene-3-carbonitrile (8e), 2-amino-4-(3-fluorophenyl)-5-oxo-4H,5H-pyrano[3,2-c]chrome-ne-3-carbonitrile (8m) and 2-amino-4-(3-bromophenyl)-5-oxo-4H,5H-dihydropyrano[3,2-c]chromene-3-carbonitrile (8n) had strong inhibitory effects on four kinds of cancer cells. However, all the compounds showed cytotoxicity to normal LO2 cells which prompts the necessary of structure modification to reduce the toxicity.

Key words: Tröger's base, Aldol-Ullmann reaction, anti-tumor activity