RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000083.xml
Synlett 2018; 29(06): 773-778
DOI: 10.1055/s-0036-1591743
DOI: 10.1055/s-0036-1591743
letter
Synthesis of Potential Anticancer 1-(1H-Indol-3-yl)isoquinolines by Silver Nitrate Mediated Tandem Reactions of 2-Alkynylbenzaldehyde Azines and Indoles
Weitere Informationen
Publikationsverlauf
Received: 22. Oktober 2017
Accepted after revision: 27. November 2017
Publikationsdatum:
02. Januar 2018 (online)
Abstract
Novel antitumor compounds featuring isoquinoline and indole moieties were synthesized by a silver nitrate promoted domino reaction involving intramolecular cyclization, nucleophilic addition of indole, and subsequent N–N bond cleavage. The transformation from readily available starting materials into an interesting class of indole-substituted isoquinolines was completed under mild conditions and by simple operations in moderate to good yields. The antitumor activity of these compounds in vitro was significantly greater than that of a reference compound, 5-fluorouracil. The products might serve as new lead compounds for drugs for the treatment of cancer.
Key words
bond cleavage - domino reaction - isoquinolines - indoles - silver nitrate - medicinal chemistrySupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591743.
- Supporting Information
-
References and Notes
- 1 Sygusch J. Brisse F. Hanessia S. Kluepfel D. Tetrahedron Lett. 1974; 15: 4021
- 2a Scott JD. Williams RM. Chem. Rev. 2002; 102: 1669
- 2b Siengalewicz P. Rinner U. Mulzer J. Chem. Soc. Rev. 2008; 37: 2676
- 2c Pu J.-Y. Peng C. Tang M.-C. Zhang Y. Guo J.-P. Song L.-Q. Hua Q. Tang G.-L. Org. Lett. 2013; 15: 3674
- 3a Kawagishi F. Toma T. Inui T. Yokoshima S. Fukuyama T. J. Am. Chem. Soc. 2013; 135: 13684
- 3b Enomoto T. Yasui Y. Takemoto Y. J. Org. Chem. 2010; 75: 4876
- 4a Wu Y.-C. Liron M. Zhu J. J. Am. Chem. Soc. 2008; 130: 7148
- 4b Chiba H. Sakai Y. Ohara A. Oishi S. Fujii N. Ohno H. Chem. Eur. J. 2013; 19: 8875
- 5a Molinski TF. Dalisay DS. Lievens SL. Saludes JP. Nat. Rev. Drug Discovery 2009; 8: 69
- 5b Peng C. Pu J.-Y. Song L.-Q. Jian X.-H. Tang M.-C. Tang G.-L. Proc. Natl. Acad. Sci. U. S. A. 2012; 109: 8540
- 6 Lin H.-R. Abraham DJ. Bioorg. Med. Chem. Lett. 2006; 16: 4178
- 7a Verma AK. Bansal S. Singh J. Tiwari RK. Sankar VK. Tandon V. Chandra R. Bioorg. Med. Chem. 2006; 14: 6733
- 7b Aneja R. Vangapandu SN. Joshi HC. Bioorg. Med. Chem. 2006; 14: 8352
- 7c Bermejo A. Andreu I. Suvire F. Léonce S. Caignard DH. Renard P. Pierré A. Enriz RD. Cortes D. Cabedo N. J. Med. Chem. 2002; 45: 5058
- 8a Vásquez D. Rodríguez JA. Theoduloz C. Verrax J. Calderon PB. Valderrama JA. Bioorg. Med. Chem. Lett. 2009; 19: 5060
- 8b Valderrama JA. Ibacache JA. Arancibia V. Rodríguez J. Theoduloz C. Bioorg. Med. Chem. 2009; 17: 2894
- 8c Gomez-Monterrey I. Campiglia P. Grieco P. Diurno MV. Bolognese A. La Colla PL. Novellino E. Bioorg. Med. Chem. 2003; 11: 3769
- 9 Chen C. Zhu Y. Liu X. Lu Z. Xie Q. Ling N. J. Med. Chem. 2001; 44: 4001
- 10a Chrzanowska M. Rozwadowska MD. Chem. Rev. 2004; 104: 3341
- 10b Giri P. Kumar GS. Mini-Rev. Med. Chem. 2010; 10: 568
- 11a Nakamura I. Yamamoto Y. Chem. Rev. 2004; 104: 2127
- 11b Zeni G. Larock RC. Chem. Rev. 2004; 104: 2285
- 11c Uchiyama M. Furuyama T. Kobayashi M. Matsumoto Y. Tanaka K. J. Am. Chem. Soc. 2006; 128: 8404
- 11d Furuyama T. Yonehara M. Arimoto S. Kobayashi M. Matsumoto Y. Uchiyama M. Chem. Eur. J. 2008; 14: 10348
- 11e Seomoon D. Lee PH. J. Org. Chem. 2008; 73: 1165
- 11f Korivi RP. Wu W.-J. Cheng C.-H. Chem. Eur. J. 2010; 16: 282
- 11g Lee K. Kim H. Mo J. Lee PH. Chem. Asian J. 2011; 6: 2147
- 11h Shi L. Ji Y. Huang W. Zhou Y. Acta Chim. Sin. (Engl. Ed.) 2014; 72: 820
- 12a Vachhani DD. Mehta VP. Modha SG. Van Hecke K. VanMeervelt L. Van der Eycken EV. Adv. Synth. Catal. 2012; 354: 1593
- 12b Roesch KR. Larock RC. J. Org. Chem. 2002; 67: 86
- 12c Zhao Y.-H. Li Y. Guo T. Tang Z. Deng K. Zhao G. Synth. Commun. 2016; 46: 355
- 12d Zhao Y.-H. Li Y. Guo T. Tang Z. Xie W. Zhao G. Tetrahedron Lett. 2016; 57: 2257
- 12e Li Y. Zhao Y. Luo M. Tang Z. Cao C. Deng K. Youji Huaxue 2016; 36: 2504
- 12f Zhao Y.-H. Luo M. Li Y. Liu X. Tang Z. Deng K. Zhao G. Chin. J. Chem. 2016; 34: 857
- 13a Chen Z. Gao L. Ye S. Ding Q. Wu J. Chem. Commun. 2012; 48: 3975
- 13b Xiao Q. Sheng J. Ding Q. Wu J. Adv. Synth. Catal. 2013; 355: 2321
- 14a Chen Z. Yang X. Wu J. Chem. Commun. 2009; 45: 3469
- 14b Ren H. Ye S. Liu F. Wu J. Tetrahedron 2010; 66: 8242
- 14c Ye S. Yang X. Wu J. Chem. Commun. 2010; 46: 5238
- 14d Li S. Luo Y. Wu J. Org. Lett. 2011; 13: 4312
- 14e Qiu G. He Y. Wu J. Chem. Commun. 2012; 3836
- 14f Ye S. Liu G. Pu S. Wu J. Org. Lett. 2012; 14: 70
- 15a Dounay AB. Overman LE. Chem. Rev. 2003; 103: 2945
- 15b Lin H. Danishefsky SJ. Angew. Chem. Int. Ed. 2003; 42: 36
- 15c Galliford CV. Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748
- 15d Shen K. Liu X.-H. Lin L.-L. Feng X.-M. Chem. Sci. 2012; 3: 327
- 16a Yu X. Yang X. Wu J. Org. Biomol. Chem. 2009; 7: 4526
- 16b Yu X. Wu J. J. Comb. Chem. 2010; 12: 238
- 17a Zhao Y.-H. Li Y. Luo M. Tang Z. Deng K. Synlett 2016; 27: 2597
- 17b Ghavtadze N. Fröhlich R. Würthwein E.-U. Eur. J. Org. Chem. 2010; 1787
- 18 Song L. Gao D. Li S. Wang Y. Liu H. Jiang Y. J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2017; 1063: 189
- 19 Zhao Y.-H. Li Y. Long Y. Zhou Z. Tang Z. Deng K. Zhang S. Tetrahedron Lett. 2017; 58: 1351
- 20 CCDC 1564922 contains the supplementary crystallographic data for compound 3a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
- 21 1-(1H-Indol-3-yl)-3-phenylisoquinoline (3a); Typical Procedure AgNO3 (50.7 mg, 0.3 mmol) and indole (2; 35.1 mg, 0.3 mmol) were added to a solution of 1,2-bis[2-(phenylethynyl)benzylidene]hydrazine (1a; 91.8 mg, 0.225 mmol) in DMSO (1.5 mL). The mixture was stirred at 80 °C until consumption of 1a was complete (TLC). The solid was removed by filtration, and the filtrate was diluted with H2O (5 mL) and extracted with EtOAc (3 × 15 mL). The organic phases were combined, dried (Na2SO4), and concentrated under reduced pressure. The residue was subjected to column chromatography [silica gel, EtOAc–hexanes (1:5)] to give a light-brown solid; yield: 74.9 mg (78%); mp 234–236 °C. IR (KBr): 3162, 1619, 1551, 1492, 1400, 1242, 1135 cm–1. 1H NMR (500 MHz, DMSO-d6 ,): δ = 11.74 (s, 1 H), 8.46 (d, J = 8.5 Hz, 1 H), 8.33–8.31 (m, 3 H), 8.09–8.01 (m, 3 H), 7.79 (t, J = 7.5 Hz, 1 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.58–7.54 (m, 3 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.24 (t, J = 7.5 Hz, 1 H), 7.17 (t, J = 7.5 Hz, 1 H). 13C NMR (125 MHz, DMSO-d6 ): δ = 155.1, 148.8, 139.1, 137.7, 136.5, 130.2, 128.8, 128.5, 127.9, 127.7, 127.3, 127.1, 126.8, 126.5, 125.4, 121.9, 120.6, 120.0, 113.6, 111.8. HRMS (ESI): m/z [M + H]+ calcd for C23H17N2: 321.1392; found: 321.1396.