Citation: Zai-Gang LUO, Dan-Dan WEI, Cheng-Tong PENG, Chen-Fu LIU, Qi-Hua CHEN, Rong-Hao ZHANG, Xue-Mei XU. Synthesis and Crystal Structure of 6-Cyclohexyl-8-methylphenanthridine[J]. Chinese Journal of Structural Chemistry, ;2021, 40(10): 1284-1290. doi: 10.14102/j.cnki.0254–5861.2011–3158 shu

Synthesis and Crystal Structure of 6-Cyclohexyl-8-methylphenanthridine

a.
State Key Laboratory of Mining Response and Disaster Prevention and Control in Deep Coal Mines, College of Chemical Engineering, Anhui University of Science and Technology, Huainan 232001, China
b.
School of Pharmaceutical Science, Gannan Medical University, Ganzhou 341000, China

Corresponding author: Zai-Gang LUO, luozi139@163.com Chen-Fu LIU, chenfu@gmu.edu.cn
Received Date: 25 February 2021
Accepted Date: 25 April 2021

Fund Project: the Natural Science Research Projects in Colleges and Universities of Anhui Province KJ2019A0116National Training Programs of Innovation and Entrepreneurship for Undergraduates 202010361076Jiangxi Education Hall Science and Technology Foundation GJJ160998

Figures(5)

The target compound IV (C₂₀H₂₁N) was synthesized through four-step reactions and structurally determined by single-crystal X-ray diffraction. The crystal of compound IV is in the orthorhombic system, space group Fdd2 with a = 41.178(19), b = 30.389(8), c = 4.8182(17) Å, β = 90°, C₂₀H₂₁N, M_r = 275.38, D_c = 1.213 g/cm³, V = 6029(4) Å³, Z = 16, F(000) = 2368, µ(MoKa) = 0.527 mm^-1, T = 240(2) K, 2200 independent reflections with 1233 observed ones (I > 2σ(I)), R = 0.1285 and wR = 0.2589 with GOF = 1.050 (R = 0.2058 and wR = 0.3055 for all data). A one-dimensional interaction model of the title compound was formed by one kind of π-π interactions between the two phenyl rings of the adjacent molecules at upper and lower levels. The inhibition to the strand transfer process of HIV-1 integrase of the target compound was also evaluated.
- phenanthridine,
- synthesis,
- crystal structure,
- HIV-1 integrase
1. [1]
  Nakanishi, T.; Suzuki, M.; Saimoto, A.; Kabasawa, T. Structural considerations of NK109, an antitumor benzo[c]phenanthridine alkaloid. J. Nat. Prod. 1999, 62, 864–867. doi: 10.1021/np990005d
2. [2]
  Abdel-Halim, O. B.; Morikawa, T.; Ando, S.; Matsuda, H.; Yoshikawa, M. New crinine-type alkaloids with inhibitory effect on induction of inducible nitric oxide synthase from crinum yemense. J. Nat. Prod. 2004, 67, 1119–1124. doi: 10.1021/np030529k
3. [3]
  Sripada, L.; Teske, J. A.; Deiters, A. Phenanthridine synthesis via [2+2+2] cyclotrimerization reactions. Org. Biomol. Chem. 2008, 6, 263–265. doi: 10.1039/B716519F
4. [4]
  Kanzawa, F.; Nishio, K.; Ishida, T.; Fukuda, M.; Kurokawa, H.; Fukumoto, H.; Nomoto, Y.; Fukuoka, K.; Bojanowski, K.; Saijo, N. Anti-tumour activities of a new benzo[c]phenanthridine agent, 2, 3-(methylenedioxy)-5-methyl-7-hydroxy-8-methoxybenzo[c]phenanthridinium hydrogensulphate dihydrate (NK109), against several drug-resistant human tumour cell lines. Br. J. Cancer. 1997, 76, 571–581. doi: 10.1038/bjc.1997.428
5. [5]
  Ishikawa, T. Benzo[c]phenanthridine bases and their antituberculosis activity. Med. Res. Rev. 2001, 21, 61–72. doi: 10.1002/1098-1128(200101)21:1<61::AID-MED2>3.0.CO;2-F
6. [6]
  Li, K.; Frankowski, K. J.; Belon, C. A.; Neuenswander, B.; Ndjomou, J.; Hanson, A. M.; Shanahan, M. A.; Schoenen, F. J.; Blagg, B. S. J.; Aubé, J.; Frick, D. N. Optimization of potent hepatitis C virus NS3 helicase inhibitors isolated from the yellow dyes thioflavine S and primuline. J. Med. Chem. 2012, 55, 3319–3330. doi: 10.1021/jm300021v
7. [7]
  Pictet, A.; Hubert, A. Ueber eine neue synthese der phenanthridinbasen. Ber. Dtsch. Chem. Ges. 1896, 29, 1182–1189. doi: 10.1002/cber.18960290206
8. [8]
  Grigg, R. D.; Van Hoveln, R.; Schomaker, J. M. Copper-catalyzed recycling of halogen activating groups via 1, 3-halogen migration. J. Am. Chem. Soc. 2012, 134, 16131–16134. doi: 10.1021/ja306446m
9. [9]
  Fan, J.; Li, L.; Zhang, J.; Xie, M. Expeditious synthesis of phenanthridines through a Pd/MnO₂-mediated C–H arylation/oxidative annulation cascade from aldehydes, aryl iodides and amino acids. Chem. Commun. 2020, 56, 2775–2778. doi: 10.1039/D0CC00300J
10. [10]
  Jiang, H.; An, X.; Tong, K.; Zheng, T.; Zhang, Y.; Yu, S. Visible-light-promoted iminyl-radical formation from acyl oximes: a unified approach to pyridines, quinolines, and phenanthridines. Angew. Chem. Int. Ed. 2015, 54, 4055–4059. doi: 10.1002/anie.201411342
11. [11]
  Zhou, Y.; Wu, C.; Dong, X.; Qu, J. Synthesis of 6-trichloromethylphenanthridines by transition metal-free radical cyclization of 2-isocyanobiphenyls. J. Org. Chem. 2016, 81, 5202–5208. doi: 10.1021/acs.joc.6b00885
12. [12]
  Wang, L.; Zhu, H.; Guo, S.; Cheng, J.; Yu, J. T. TBHP-promoted sequential radical silylation and aromatisation of aryl isonitriles with silanes. Chem. Commun. 2014, 50, 10864–10867. doi: 10.1039/C4CC04773G
13. [13]
  Fang, B.; Hou, J.; Tian, J.; Yu, W.; Chang, J. Synthesis of phenanthridines by I2-mediated sp³ C–H amination. Org. Biomol. Chem. 2020, 18, 3312–3323. doi: 10.1039/D0OB00433B
14. [14]
  Li, G.; Kong, X.; Liang, Q.; Lin, L.; Yu, K.; Xu, B.; Chen, Q. Metal-free electrochemical coupling of vinyl azides: synthesis of phenanthridines and β-ketosulfones. Eur. J. Org. Chem. 2020, 6135–6145.
15. [15]
  Zhang, B.; Studer, A. Recent advances in the synthesis of nitrogen heterocycles via radical cascade reactions using isonitriles as radical acceptors. Chem. Soc. Rev. 2015, 44, 3505–3521. doi: 10.1039/C5CS00083A
16. [16]
  Dayam, R.; Deng, J.; Neamati, N. HIV-1 integrase inhibitors: 2003—2004 update. Med. Res. Rev. 2006, 26, 271−309. doi: 10.1002/med.20054
17. [17]
  Dayam, R.; Gundla, R.; Al-Mawsawi, L. Q.; Neamti, N. HIV-1 integrase inhibitors: 2005—2006 update. Med. Res. Rev. 2008, 28, 118−154. doi: 10.1002/med.20116
18. [18]
  Peytou, V.; Condom, R.; Patino, N.; Guedj, R.; Aubertin, A. M.; Gelus, N.; Bailly, C.; Terreux, R.; Cabrol-Bass, D. Synthesis and antiviral activity of Ethidium-Arginine conjugates directed against the TAR RNA of HIV-1. J. Med. Chem. 1999, 42, 4042–4053. doi: 10.1021/jm980728e
19. [19]
  Luo, Z. G.; Zeng, C. C.; Yang, L. F.; He, H. Q.; Wang, C. X.; Hu, L. M. Synthesis of 6-sulfamoyl-4-oxoquinoline-3-carboxylic acid derivatives as integrase antagonists with anti-HIV activity. Chin. Chem. Lett. 2009, 20, 789–792. doi: 10.1016/j.cclet.2009.03.014
20. [20]
  Luo, Z.; Zhao, Y.; Ma, C.; Li, Z.; Xu, X.; Hu, L.; Huang, N.; He, H. Synthesis, biological evaluation and molecular docking of calix[4]arene-based β-diketo derivatives as HIV-1 integrase inhibitors. Arch. Pharm. 2015, 348, 206–213. doi: 10.1002/ardp.201400390
21. [21]
  Xu, X. M.; Luo, Z. G.; Han, X. X.; Liu, Q. N.; Li, R. Synthesis, crystal structure and biological activity of dimethyl 1-methyl-1, 4-dihydroquinoline-3, 4-dicarboxylate and tetramethyl pyrrolo[1, 2-a]quinoline-2, 3, 4, 5-tetracarboxylate. Chin. J. Struct. Chem. 2020, 39, 1271−1276.
22. [22]
  Sha, W.; Yu, J. T.; Jiang, Y.; Yang, H.; Chen, J. The benzoyl peroxide-promoted functionalization of simple alkanes with 2-aryl phenyl isonitrile. Chem. Commun. 2014, 50, 9179−9181. doi: 10.1039/C4CC03304C
23. [23]
  Bruker 2000, SMART (Version 5.0), SAINT-plus (Version 6), SHELXTL (Version 6.1), and SADABS (Version 2.03); Bruker AXS Inc. : Madison, WI.
24. [24]
  Gu, S. J.; Qin, D. B.; Jin, L. H. Synthesis and crystal structure of calyx[4]arene bearing a 1, 8-bis(propoxy) anthracene-9, 10-dione. Chin. J. Struct. Chem. 2008, 27, 1035−1038.
25. [25]
  Sheldrick, G. M. SHELXS-97, Program for X-ray Crystal Structure Solution. University of Göttingen, Germany 1997.
26. [26]
  Sheldrick, G. M. SHELXL-97, Program for the Refinement of Crystal Structure. University of Göttingen: Göttingen, Germany 1997.
27. [27]
  He, H. Q.; Ma, X. H.; Liu, B.; Chen, W. Z.; Wang, C. X.; Chen, S. H. A novel high-throughput format assay for HIV-1 integrase strand transfer reaction using magnetic beads. Acta Pharmacologica. Sinica 2008, 29, 397−404. doi: 10.1111/j.1745-7254.2008.00748.x
1. [1]
  Chao LIU , Jiang WU , Zhaolei JIN . Synthesis, crystal structures, and antibacterial activities of two zinc(Ⅱ) complexes bearing 5-phenyl-1H-pyrazole group. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1986-1994. doi: 10.11862/CJIC.20240153
2. [2]
  Yao HUANG , Yingshu WU , Zhichun BAO , Yue HUANG , Shangfeng TANG , Ruixue LIU , Yancheng LIU , Hong LIANG . Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359
3. [3]
  Lulu DONG , Jie LIU , Hua YANG , Yupei FU , Hongli LIU , Xiaoli CHEN , Huali CUI , Lin LIU , Jijiang WANG . Synthesis, crystal structure, and fluorescence properties of Cd-based complex with pcu topology. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 809-820. doi: 10.11862/CJIC.20240171
4. [4]
  Xiaoxia WANG , Ya'nan GUO , Feng SU , Chun HAN , Long SUN . Synthesis, structure, and electrocatalytic oxygen reduction reaction properties of metal antimony-based chalcogenide clusters. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1201-1208. doi: 10.11862/CJIC.20230478
5. [5]
  Xiaoling WANG , Hongwu ZHANG , Daofu LIU . Synthesis, structure, and magnetic property of a cobalt(Ⅱ) complex based on pyridyl-substituted imino nitroxide radical. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 407-412. doi: 10.11862/CJIC.20240214
6. [6]
  Kaimin WANG , Xiong GU , Na DENG , Hongmei YU , Yanqin YE , Yulu MA . Synthesis, structure, fluorescence properties, and Hirshfeld surface analysis of three Zn(Ⅱ)/Cu(Ⅱ) complexes based on 5-(dimethylamino) isophthalic acid. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1397-1408. doi: 10.11862/CJIC.20240009
7. [7]
  Jia JI , Zhaoyang GUO , Wenni LEI , Jiawei ZHENG , Haorong QIN , Jiahong YAN , Yinling HOU , Xiaoyan XIN , Wenmin WANG . Two dinuclear Gd(Ⅲ)-based complexes constructed by a multidentate diacylhydrazone ligand: Crystal structure, magnetocaloric effect, and biological activity. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 761-772. doi: 10.11862/CJIC.20240344
8. [8]
  Ruikui YAN , Xiaoli CHEN , Miao CAI , Jing REN , Huali CUI , Hua YANG , Jijiang WANG . Design, synthesis, and fluorescence sensing performance of highly sensitive and multi-response lanthanide metal-organic frameworks. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 834-848. doi: 10.11862/CJIC.20230301
9. [9]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
10. [10]
  Xiumei LI , Yanju HUANG , Bo LIU , Yaru PAN . Syntheses, crystal structures, and quantum chemistry calculation of two Ni(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 2031-2039. doi: 10.11862/CJIC.20240109
11. [11]
  Xiumei LI , Linlin LI , Bo LIU , Yaru PAN . Syntheses, crystal structures, and characterizations of two cadmium(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 613-623. doi: 10.11862/CJIC.20240273
12. [12]
  Yan XU , Suzhi LI , Yan LI , Lushun FENG , Wentao SUN , Xinxing LI . Structure variation of cadmium naphthalene-diphosphonates with the changing rigidity of N-donor auxiliary ligands. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 395-406. doi: 10.11862/CJIC.20240226
13. [13]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
14. [14]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
15. [15]
  Huan ZHANG , Jijiang WANG , Guang FAN , Long TANG , Erlin YUE , Chao BAI , Xiao WANG , Yuqi ZHANG . A highly stable cadmium(Ⅱ) metal-organic framework for detecting tetracycline and p-nitrophenol. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 646-654. doi: 10.11862/CJIC.20230291
16. [16]
  Meirong HAN , Xiaoyang WEI , Sisi FENG , Yuting BAI . A zinc-based metal-organic framework for fluorescence detection of trace Cu²⁺. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1603-1614. doi: 10.11862/CJIC.20240150
17. [17]
  Shuyan ZHAO . Field-induced Co^Ⅱ single-ion magnet with pentagonal bipyramidal configuration. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1583-1591. doi: 10.11862/CJIC.20240231
18. [18]
  Yinling HOU , Jia JI , Hong YU , Xiaoyun BIAN , Xiaofen GUAN , Jing QIU , Shuyi REN , Ming FANG . A rhombic Dy₄-based complex showing remarkable single-molecule magnet behavior. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 605-612. doi: 10.11862/CJIC.20240251
19. [19]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
20. [20]
  Zhaodong WANG . In situ synthesis, crystal structure, and magnetic characterization of a trinuclear copper complex based on a multi-substituted imidazo[1,5-a]pyrazine scaffold. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 597-604. doi: 10.11862/CJIC.20240268

Get Citation

PDF

XML

Metrics

PDF Downloads(2)
Abstract views(349)
HTML views(18)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142