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Nucleophilic Reaction of 2-Phenyl-4-quinolones with Methyl Iodide and Preparation of Its Derivatives  

Oh, Mi-Jung (College of Pharmacy, Duksung Women's University)
Park, Myung-Sook (College of Pharmacy, Duksung Women's University)
Publication Information
YAKHAK HOEJI / v.52, no.6, 2008 , pp. 514-519 More about this Journal
Abstract
We developed a convenient synthetic route to 3-alkylated 2-phenyl-4-quinolone derivatives (4a-h and 5a-c), which were expected to retain antitumor activity. A series of 2,3-dihydro-2-hydroxy-2-phenyl-4-quinolones (3a-h) was synthesized through dehydration, dealcoholation and hydration using acid-catalyzed one-pot reaction from anilines and ethyl benzoylacetates. 3-Methyl (or 3,3-dimethyl)-2-phenyl-4-quinolone derivatives 4 and 5 were synthesized from 3a-h through the methylation using methyl iodide. Formation of quinolone nucleus was undertaken with p-toluenesulfonic acid (p-TSA) at $90{\sim}110^{\circ}C$ in toluene for 3${\sim}$7.5 hr over the Dean-Stark apparatus. The key intermediates in these preparations are ${\beta}$-ketoesters 2a-h, which can be readily obtained from the corresponding anilines 1a-e by reaction with ethyl bezoylacetates.
Keywords
3-alkyl-2-phenyl-4-quinolone; C-methylation; monomethylated quinolones; dimethylated quinolones;
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1 Gobbi, S., Rampa, A., Bisi, A., Belluti, F., Piazzi, L., Valenti, P., Caputo, A., Zampiron, A. and Carrara, M. : Synthesis and biological evaluation of 3-alkoxy-analogues of flavone-8-acetic acid. J. Med. Chem. 46, 3662 (2003)   DOI   ScienceOn
2 Park, M. S. and Lee, J. I. : Synthesis of new 2,3-dihydro-2-phenyl-4-quinolone derivatives; aza analogs of flavanone. Bull. Korean Chem. Soc. 25, 1269 (2004)   DOI
3 Park, M. S. : Synthesis of asymmetric dmer of qinolone drivatives using p-TSA. Yakhak Hoeji 48(3), 202 (2004)
4 Kim, J. H. and Park, M. S. : Synthesis of novel 2,3-dihydro-2-phenylquinolone dimers uing ${\beta}$-ketoester and N-alkylamine. Bull. Korean Chem. Soc. 27(8), 1249 (2006)   DOI
5 Watterson, S. H., Carlsen, M., Dhar, T. G. M., Shen, Z., Pitts, W. J., Gu, H. H., Norris, D., Chorba, J., Chen, P., Cheny, D., Witmer, M., Fleener, C. A., Rouleau, K., Townsend, R., Hollenbaugh, D. L. and Iwanowicz, E. J. : Novel inhibitors of IMPDH: a highly potent and selective quinolone-based series. Bioorganic & Medicinal Chemistry Letters 13, 543 (2003)   DOI   ScienceOn
6 Xia, Y., Yang, Z. Y., Xia, P., Bastow, K. F., Nakanishi, P. N., Hamel, E., Brossi, A. and Lee, K. H. : Antitumor agents. Part 226: Synthesis and cytotoxicity of 2-phenyl-4-quinolone acetic acids and their esters. Bioorganic & Medicinal Chemistry Letters 13, 2891 (2003)   DOI   ScienceOn
7 Bauvois, B., Puiffe, M. L., Bongui, J. B., Pailat, S., Monneret, C. and Dauzonne, D. : Synthesis and biological evaluation of novel flavone-8-acetic acid derivatives as reversible inhibitors of aminopeptidase N/CD13. J. Med. Chem. 46, 3900 (2003)   DOI   ScienceOn
8 Li, L., Wang, H. K., Kuo, S. C., Wo, T. S., Lednicer, D., Lin, C. M., Hamel, E. and Lee, K. H. : Antitumor agents. 150. 2',3',4',5',5,6,7-substituted 2-phenyl-4-quinolones and related compounds: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 37, 1126 (1994)   DOI   ScienceOn
9 Li, L., Wang, H. K., Kuo, S. C., Wu, T. S., Mauger, A., Lin, C. M., Hamel, E. and Lee, K. H. : Antitumor agents. 155. Synthesis and biological evaluation of 3',6,7-substituted 2-phenyl-4-quinolones as antimicrotubule agents. J. Med. Chem. 37, 3400 (1994)   DOI   ScienceOn
10 Kuo, S. C., Lee, H. Z., Juang, J. P., Lin, Y. T., Wu, T. S., Chang, J. J., Lednicer, D., Paull, K. D., Lin, C. M., Hamel, E. and Lee, K. H. : Synthesis and cytotoxicity of 1,6,7,8-substituted 2-(4'-substituted phenyl)-4-quinolones and related compounds: Identification as antimitotic agents interacting with tubulin. J. Med. Chem. 36, 1146 (1993)   DOI   ScienceOn
11 Seo, H. J. and Surh, Y. J. : Eupatilin, a pharmacologically active flavone derived from artemisia plants, induces apoptosis in human promyelocytic leukemia cells. Mutation Rearch 496, 191 (2001)   DOI   ScienceOn