Download PDF
Synthesis 2009(24): 4219-4225  
DOI: 10.1055/s-0029-1217049
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Convenient Procedure for the Synthesis of New α-Pyridinyl-Substituted 7H-Indeno[2,1-c]quinoline Derivatives Based on a Three-Component Imino Diels-Alder Reaction

Vladimir V. Kouznetsov*a, Arnold R. Romero Bohórqueza, Luis Astudillo Saavedrab
a Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Colombia
Fax: +57(76)349069; e-Mail: kouznet@uis.edu.co;
b Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla: 747, Talca, Chile
Further Information

Publication History

Received 17 June 2009
Publication Date:
19 October 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

A new series of α-pyridinyl-substituted indeno[2,1-c]quinoline derivatives was prepared with good yields according to a two-step synthesis. The first and key step involves the formation of the ring via three-component imino Diels-Alder cycloaddition between an aniline, pyridine-2-carbaldehyde, and indene using boron trifluoride-diethyl ether complex as a catalyst to produce the corresponding 5,6,6a,11b-tetrahydroindeno[2,1-c]quinolines. The second step consisted of their oxidation with powdered sulfur to obtain the corresponding indeno[2,1-c]quinolines, analogues of DNA topoisomerase inhibitor TAS-103.

Key words

cycloaddition - multicomponent reaction - imino Diels-Alder reaction - indeno[2,1-c]quinolines

    References

  • 1a Kouznetsov V. Palma A. Ewert C. Varlamov A. J. Heterocycl. Chem.  1998,  35:  761 
    Search in Google Scholar
  • 1b Katritzky AR. Rachwal S. Rachwal B. Tetrahedron  1996,  52:  15031 
    Search in Google Scholar
  • 1c Carling RW. Leeson PD. Moseley AM. Baker R. Forster AC. Grimwood S. Kemp JA. Marshall GR. J. Med. Chem.  1992,  35:  1942 
    Search in Google Scholar
  • 1d Cai SX. Zhou Z.-L. Huang J.-C. Whittermore ER. Egbuwoku ZO. Lü Y. Hawkinson JE. Woodward RM. Keana JFW. J. Med. Chem.  1996,  39:  3248 
    Search in Google Scholar
  • 2a Bendale P. Olepu S. Kumar SP. Buldule V. Rivas K. Nallan L. Smart B. Yokoyama K. Ankala S. Rao PP. Floyd D. Lombardo L. Williams DK. Buckner FS. Chakrabarti D. Verlinde CMJ. Van Voorhis WC. Gelb MH. J. Med. Chem.  2007,  50:  4585 
    Search in Google Scholar
  • 2b Jacquemond-Collet I. Benoit-Vical F. Valentin A. Stanislas E. Mallie M. Fouraste I. Planta Med.  2002,  68:  68 
    Search in Google Scholar
  • 3a Nishiyama TT. Hashiguchi YY. Sakata ST. Sakaguchi TT. Polym. Degrad. Stab.  2003,  79:  225 
    Search in Google Scholar
  • 3b Dorey G. Lockhart B. Lestage P. Casara P. Bioorg. Med. Chem. Lett.  2000,  10:  9350 
    Search in Google Scholar
  • 4 Calhoun W. Carlson RP. Crossley R. Datko LJ. Dietrich S. Heatherington K. Marshall LA. Meade PJ. Opalko A. Shepherd RG. J. Med. Chem.  1995,  38:  1473 
    CrossrefSearch in Google Scholar
  • 5a Gelderblom H. Sparreboom A. In Drugs Affecting Growth of Tumours   Pinedo HM. Smorenburg CH. Birkhauser Verlag; Switzerland: 2006.  p.83 
  • 5b Denny WA. Baguley BC. Curr. Top. Med. Chem.  2003,  3:  339 
    Search in Google Scholar
  • 6a Pommier Y. Nat. Rev. Cancer  2006,  6:  789 
    Search in Google Scholar
  • 6b Priel E. Showalter SD. Roberts M. Oroszlan S. Blair DG. J. Virol.  1991,  65:  4137 
    Search in Google Scholar
  • 6c Herben VMM. ten Bokkel HWW. Schellens JHM. Beijnen JH. Pharm. World Sci.  1998,  20:  161 
    Search in Google Scholar
  • 7a Li Q.-Y. Zu Y.-G. Shi R.-Z. Yao L.-P. Curr. Med. Chem.  2006,  13:  2021 
    Search in Google Scholar
  • 7b Martínez R. Chacón-García L. Curr. Med. Chem.  2005,  12:  127 
    Search in Google Scholar
  • 7c Liew ST. Yang LX. Curr. Pharm. Des.  2008,  14:  1078 
    Search in Google Scholar
  • 7d Yount G. Yang Y. Wong B. Wang HJ. Yang LX. Anticancer Res.  2007,  27:  3173 
    Search in Google Scholar
  • 8a Denny WA. Baguley BC. Curr. Top. Med. Chem.  2003,  3:  339 
    Search in Google Scholar
  • 8b Minderman H. Wrzosek C. Cao S.-S. Utsugi T. Kobunai T. Yamada Y. Rustum YM. Cancer Chemother. Pharmacol.  2000,  45:  78 
    Search in Google Scholar
  • 9a Twelves CJ. Gardner C. Flavin A. Sludden J. Dennis I. de Bono J. Beale P. Vasey P. Hutchison C. Macham MA. Rodríguez A. Judson I. Bleehen NM. Br. J. Cancer  1999,  80:  1786 
    Search in Google Scholar
  • 9b Ohyama T. Li Y. Utsugi T. Irie S. Yamada Y. Sato T. Jpn. J. Cancer Res.  1999,  44:  691 
    Search in Google Scholar
  • 10a Ewesuedo RB. Iyer L. Das S. Koenig A. Mani S. Vogelzang NJ. Schilsky RL. Brenckman W. Ratain MJ. J. Clin. Oncol.  2001,  19:  2084 
    Search in Google Scholar
  • 10b Ishida K. Asao T. Biochim. Biophys. Acta  2002,  1587:  155 
    Search in Google Scholar
  • 10c Osman S. Luthra SK. Brady F. Hume SP. Brown G. Harte RJA. Matthews JC. Denny WA. Baguley BC. Jones T. Price PM. Cancer Res.  1997,  57:  2172 
    Search in Google Scholar
  • 10d Dittrich C. Dieras V. Kerbrat P. Punt C. Sorio R. Copanigro F. Paoletti X. Balincourt C. Lacombe D. Fumoleau P. Invest. New Drugs  2003,  21:  347 
    Search in Google Scholar
  • 11a Anzini M. Cappelli A. Vomero S. J. Heterocycl. Chem.  1991,  28:  1809 
    Search in Google Scholar
  • 11b Cappelli A. Anzini M. Vomero S. Canullo L. Mennuni L. Makovec F. Doucet E. Hamon M. Menziani MC. De Benedetti PG. Bruni G. Romeo MR. Giorgi G. Donati A. J. Med. Chem.  1999,  42:  1556 
    Search in Google Scholar
  • 12a Kouznetsov VV. Romero BAR. Stashenko EE. Tetrahedron Lett.  2007,  48:  8855 
    Search in Google Scholar
  • 12b Sridharan V. Perumal PT. Avendaño PC. Menéndez JC. Org. Biomol. Chem.  2007,  5:  1351 
    Search in Google Scholar
  • 12c Akiyama T. Morita H. Fuchibe K. J. Am. Chem. Soc.  2006,  128:  13070 
    Search in Google Scholar
  • 12d Legros J. Crousse B. Qurévitch M. Bonnet-Delpon D. Synlett  2006,  1899 
  • 12e Akiyama T. Nakashima S. Yokota K. Fuchibe K. Chem. Lett.  2004,  33:  922 
    Search in Google Scholar
  • For a recent review of imino Diels-Alder reactions, see:
  • 13a Kouznetsov VV. Tetrahedron  2009,  65:  2721 
    Search in Google Scholar
  • 13b Glushkov VA. Tolstikov AG. Russ. Chem. Rev. (Engl. Transl.)  2008,  77:  137 
    Search in Google Scholar
  • 13c Olsen J.-C. Oh T. Tetrahedron  2001,  57:  6099 
    Search in Google Scholar
  • 14 Subba Reddy BV. Srinivas R. Yadav JS. Ramalingam T. Synth. Commun.  2001,  31:  1075 
    CrossrefSearch in Google Scholar
  • 15 Babu G. Perumal PT. Tetrahedron Lett.  1998,  39:  3225 
    CrossrefSearch in Google Scholar
  • 16 Kobayashi S. Ishitani H. Nagayama S. Synthesis  1995,  1195 
    Thieme Connect
  • 17 Yadav JS. Subba Reddy BV. Srinivas R. Madhuri Ch. Ramalingam T. Synlett  2001,  240 
  • 18 Kobayashi S. Nagayama S. J. Am. Chem. Soc.  1996,  118:  8977 
    CrossrefSearch in Google Scholar
  • 19a Kiselyov A. Smith L. Armstrong R. Tetrahedron  1998,  54:  5089 
    Search in Google Scholar
  • 19b Kiselyov A. Smith L. Virgilio A. Armstrong R. Tetrahedron  1998,  54:  7987 
    Search in Google Scholar
  • 20 Kouznetsov VV. Ochoa Puentes C. Zachinno SA. Gupta M. Romero BAR. Sortino M. Vásquez Y. Bahsas A. Amaro-Luis J. Lett. Org. Chem.  2006,  3:  300 
    CrossrefSearch in Google Scholar
  • 21a Vargas MLY. Castelli MV. Kouznetsov VV. Urbina GJM. López SN. Sortino M. Enriz RD. Ribas JC. Zacchino SA. Bioorg. Med. Chem.  2003,  11:  1531 
    Search in Google Scholar
  • 21b Kouznetsov VV. Rivero Castro J. Ochoa Puentes C. Stashenko EE. René Martinez J. Ochoa C. Montoro Pereira D. Nogal Ruiz JJ. Fernández Portillo C. Muelas Serrano S. Gómez Barrio A. Bahsas A. Amaro-Luis J. Arch. Pharm. (Weinheim, Ger.)  2005,  338:  32 
    Search in Google Scholar
  • 21c Kouznetsov VV. Zubkov FI. Mora U. Nikitina EV. Synthesis  2007,  375 
22

Full crystallographic data for indenoquinoline 7c will be published elsewhere.

23

Another commonly used oxidant, DDQ in MeCN, was less efficient for this process due poor solubility of the starting tetrahydroindeno[2,1-c]quinolines.

24

Antitumoral and cytotoxic activities for this new series of compounds will be published in due course.