PDF herunterladen
Synlett 2003(10): 1533-1535
DOI: 10.1055/s-2003-40843
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Synthetic Route to Homocarbonyltopsentine

Cyril Montagne, Guy Fournet, Benoît Joseph*
Laboratoire de Chimie Organique 1, UMR-CNRS 5622, Université Claude Bernard - Lyon 1, CPE Bâtiment 308, 43, Boulevard du 11 Novembre 1918, 69622 Villeurbanne cedex, France
Fax: +33(4)72431214; e-Mail: benoit.joseph@univ-lyon1.fr;
Weitere Informationen

Publikationsverlauf

Received 19 May 2003
Publikationsdatum:
24. Juli 2003 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Efficient synthesis of homocarbonyltopsentine Ia, starting from readily available triiodoimidazole 9 and 3-formylindoles 2 and 18 is described. The key steps of the synthesis are selective halogen-metal exchanges at the imidazole nucleus and subsequent addition to formylated indoles.

Key words

indoles - metalation - regioselectivity - addition reactions - alkaloids

    References

  • 1 Jacobs RS, Pomponi S, Gunasekera S, and Wright A. inventors; PCT Int. Appl. WO  9818466.  ; Chem. Abstr. 1998, 129, 587
  • 2a Casapullo A. Bifulco G. Bruno I. Riccio R. J. Nat. Prod.  2000,  63:  447 
    PubMedGoogle Scholar
  • 2b Faulkner DJ. Nat. Prod. Rep.  2002,  19:  1 
    PubMedGoogle Scholar
  • 3a Phife DW. Ramos RA. Feng M. King I. Gunasekera SP. Wright A. Patel M. Pachter JA. Coval SJ. Bioorg. Med. Chem. Lett.  1996,  6:  2103 
    Google Scholar
  • 3b Jiang B. Xiong W.-N. Yang C.-G. Jiang H.-L. Cheng F. Chen K.-X. Bioorg. Med. Chem.  2002,  10:  2775 
    Google Scholar
  • See for example:
  • 4a Jiang B. Yang C.-G. Wang J. J. Org. Chem.  2001,  66:  7560 
    CrossrefGoogle Scholar
  • 4b Miyake FY. Yakushijin K. Horne DA. Org. Lett.  2000,  2:  3185 
    CrossrefGoogle Scholar
  • 4c Janosik T. Johnson A.-L. Bergman J. Tetrahedron  2002,  58:  2813 
    CrossrefGoogle Scholar
  • 5 For a review on metalation of the imidazoles see: Iddon B. Ngochindo RI. Heterocycles  1994,  38:  2487 
    CrossrefGoogle Scholar
  • 6a Iddon B. Lim BL. J. Chem. Soc., Perkin Trans. 1  1983,  735 
    CrossrefPubMedGoogle Scholar
  • 6b Abarbri M. Thibonnet J. Bérillon L. Dehmel F. Rottländer M. Knochel P. J. Org. Chem.  2000,  65:  4618 
    CrossrefPubMedGoogle Scholar
  • 7a Ngochindo RI. J. Chem. Res., Synop.  1990,  58 
    Google Scholar
  • 7b Lipshutz BH. Vaccaro W. Huff B. Tetrahedron Lett.  1986,  27:  4095 
    Google Scholar
  • 8 LaMattina JL. Mularski CJ. J. Org. Chem.  1986,  51:  413 
    CrossrefGoogle Scholar
  • 9 Achab S. Tetrahedron Lett.  1996,  37:  5503 ; and references cited therein
    Google Scholar
  • 10 Turner RM. Ley SV. Lindell SD. Synlett  1993,  748 
    Artikel in Thieme ConnectGoogle Scholar
  • 12 Synthesised by formylation (POCl3, DMF) and protection (Boc2O, DMAP, acetonitrile) of 6-benzyloxyindole prepared according to; Moody CJ. J. Chem. Soc., Perkin Trans. 1  1984,  1333 
    Google Scholar
11

All new compounds gave satisfactory spectroscopic and analytical data. Selected spectroscopic data: 16: white solid, mp >210 °C; IR (KBr): 3198, 1609, 1590, 1512, 1415, 1110, 859 cm-1; 1H NMR (300 MHz, DMSO-d 6): δ 7.22-7.30 (m, 4 H, HAr), 7.53-7.59 (m, 2 H, HAr), 8.02 (s, 1 H, HAr), 8.37-8.40 (m, 2 H, HAr), 8.97 (s, 1 H, HAr), 9.14 (s, 1 H, HAr), 12.00 (s, 1 H, NH), 12.21 (s, 1 H, NH), 13.70 (s, 1 H, NH); 13C NMR (75 MHz, DMSO-d 6): δ 112.2 (CH), 112.5 (CH), 113.4 (C), 114.9 (C), 121.6 (CH), 121.7 (2 CH), 122.3 (CH), 122.9 (CH), 123.2 (CH), 124.3 (CH), 126.5 (C), 126.7 (C), 135.7 (CH), 136.2 (C), 136.3 (C), 137.1 (CH), 143.3 (C), 145.5 (C), 176.5 (CO), 181.6 (CO); MS (ESI): m/z 355 (M + H+); HRMS (LSIMS) for C21H15N4O2: calculated: 355.1195, found: 355.1195. Ia: yellow solid, mp >210 °C; IR (KBr): 3380, 3200, 1592, 1572, 1525, 1430, 1120, 868 cm-1; 1H NMR (300 MHz, DMSO-d 6): δ 6.78 (dd, 1 H, J = 1.7 Hz, 8.6 Hz, HAr), 6.92 (br s, 1 H, HAr), 7.20-7.28 (m, 2 H, HAr), 7.53-7.56 (m, 1 H, HAr) 8.01 (s, 1 H, HAr), 8.15 (d, 1 H, J = 8.6 Hz, HAr), 8.38-8.41 (m, 1 H, HAr), 8.96 (br s, 2 H, HAr), 9.33 (s, 1 H, OH), 11.84 (s, 1 H, NH), 11.99 (s, 1 H, NH), 13.63 (s, 1 H, NH); 13C NMR (75 MHz, DMSO-d 6): δ 97.6 (CH), 112.2 (CH), 112.3 (CH), 113.6 (C), 114.9 (C), 119.4 (C), 121.7 (CH), 121.8 (CH), 122.1 (CH), 122.9 (CH), 124.2 (CH), 126.8 (C), 135.7 (CH), 135.9 (CH), 136.2 (C), 137.6 (C), 143.3 (C), 145.6 (C), 154.4 (C), 176.3 (CO), 181.6 (CO); MS (ESI): m/z 371 (M + H+); HRMS (LSIMS) for C21H15N4O3: calculated: 371.1144, found: 371.1143.