PDF herunterladen
Synlett 2004(8): 1414-1418  
DOI: 10.1055/s-2004-829053
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Simple Biomimetic Route to Nonsymmetric Pyrazines

Edgar Haak*, Ekkehard Winterfeldt
Department of Organic Chemistry, University of Hannover, Schneiderberg 1B, 30167 Hannover, Germany
Fax: +49(531)3915388; e-Mail: e.haak@tu-bs.de;
Weitere Informationen

Publikationsverlauf

Received 17 October 2003
Publikationsdatum:
08. Juni 2004 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

The condensation of enaminoketone 8 to α-hydroxyketones gives rise to nonsymmetric pyrazines. This may be of relevance for the biosynthesis of this heterocycle in the cephalostatins and ritterazines.

Key words

hydroxyketones - pyrazine synthesis - cephalostatins - biosynthesis - pyrylium salts

    References

  • 1 Pettit GR. Inoue M. Kamano Y. Herald DL. Arm C. Dufresne C. Christie ND. Schmidt JM. Doubek DL. Krupta TS. J. Am. Chem. Soc.  1988,  110:  2006 
    CrossrefGoogle Scholar
  • 2 Fukuzawa S. Matsunaga S. Fusetani N. J. Org. Chem.  1994,  59:  6164 
    Google Scholar
  • 3 Paull KD. Shoemaker RH. Hodes L. Monks A. Scudiero DA. Rubinstein L. Plowman J. Boyd MR. J. Natl. Cancer Inst.  1989,  81:  1088 
    CrossrefPubMedGoogle Scholar
  • 4 Ganesan A. Studies in Nat. Prod. Chem.  1996,  18:  875 
    Google Scholar
  • 5 Habermehl G. Hamman PE. Krebs HC. In Naturstoffchemie   Springer; Berlin: 2002.  p.58 
    Google Scholar
  • 6 Flemming S. Dissertation   University of Hannover; Germany: 1991. 
    Google Scholar
  • 7 Guo C. Lacour TG. Fuchs PL. Bioorg. Med. Chem. Lett.  1999,  9:  419 
    CrossrefGoogle Scholar
  • 8 Jautelat R. Müller-Fahrnow A. Winterfeldt E. Chem.-Eur. J.  1992,  5:  1226 
    Google Scholar
  • 9 Drögemüller M. Jautelat R. Winterfeldt E. Angew. Chem.  1996,  108:  1669 
    Google Scholar
  • 10 Bladon P. Mc Meekin W. Williams IA. J. Chem. Soc.  1963,  5727 
    Google Scholar
  • 11 Welzel P. Janssen B. Duddeck H. Liebigs Ann. Chem.  1981,  546 
    Google Scholar
  • 12 Chinn LJ. J. Org. Chem.  1967,  32:  687 
    Google Scholar
  • 13 Hamann PE. Habermehl GG. Z. Naturforsch.  1987,  426:  781 
    Google Scholar
  • 14 Jautelat R. Winterfeldt E. Müller-Fahrnow A. J. Prakt. Chem.  1996,  338:  695 
    CrossrefGoogle Scholar
  • Interestingly, even three new methods that were described only very recently are not easily adopted for steroid precursors. See:
  • 15a Emoto T. Kubosaki N. Yamagiwa Y. Kamikawa T. Tetrahedron Lett.  2000,  41:  355 
    CrossrefGoogle Scholar
  • 15b Lenoir I. Smith ML. J. Chem. Soc., Perkin Trans. 1  2000,  641 
    CrossrefGoogle Scholar
  • 15c Marjo CE. Bishop R. Craig DC. Scudder ML. Eur. J. Org. Chem.  2001,  863 
    CrossrefGoogle Scholar
  • 16 Kramer A. Ullmann U. Winterfeldt E. J. Chem. Soc., Perkin Trans. 1  1993,  2865 
    CrossrefGoogle Scholar
  • 17 Jeong JU. Sutton SC. Kim S. Fuchs PL. J. Am. Chem. Soc.  1995,  117:  10157 
    CrossrefGoogle Scholar
  • 18 Heathcock CH. Smith SC. J. Org. Chem.  1992,  57:  6379 
    Google Scholar
  • 19 Heathcock CH. Smith SC. J. Org. Chem.  1994,  59:  6828 
    CrossrefGoogle Scholar
  • 20 Fuchs PL. LaCour TG. Guo C. Bhandaru S. Boyd MR. J. Am. Chem. Soc.  1998,  120:  692 
    CrossrefGoogle Scholar
  • 21 Gryszkiewicz-Wojtkielewicz A. Jastrzebska I. Morzycki JW. Romanowska DB. Curr. Org. Chem.  2003,  7:  1257 
    CrossrefGoogle Scholar
  • 22 Drögemüller M. Flessner T. Jautelat R. Scholz U. Winterfeldt E. Eur. J. Org. Chem.  1998,  2811 
    CrossrefGoogle Scholar
  • 23 Wiemann MJ. Vinot N. Villadary M. Bull. Soc. Chim. Fr.  1965,  3476 
    Google Scholar
  • 24 Scholz U. Winterfeldt E. Nat. Prod. Rep.  2000,  17:  349 
    CrossrefPubMedGoogle Scholar
  • 28 Doyle TW. Martel A. Luh BY. Can. J. Chem.  1977,  55:  2708 
    Google Scholar
25

The low yield observed may well be due to methanolysis of the O-acetate under the reaction conditions.

26

It is mentioned in passing that the well-known oxidative degradation of the furan ring [28] to a carboxylic acid could lead to pyrazine bis-carboxylic acids and derivatives thereof.

27

Reaction Procedure to Form Nonsymmetric Pyrazine 29: Enaminoketone 13 9 (80 mg, 0.18 mmol) and NH4OAc (35 mg, 0.45 mmol) were dissolved in moist MeOH (5 mL, <0.1% H2O) and refluxed for 30 min. A solution of α-hydroxyketone 28 (80 mg, 0.18 mmol) in CH2Cl2 (0.6 mL) was added and the resulting suspension was refluxed for additional 90 min. The mixture was quenched with H2O, extracted with CH2Cl2, and the organic layer was washed with brine and dried over MgSO4. After removal of the solvent, the residue was purified by column chromatography on silica gel to give 29 (43 mg, 28%) as a white solid. 1H NMR (400 MHz, CDCl3): δ = 5.48 (s br, 1 H), 4.78 (dd, J = 7.9 Hz, 2.0 Hz, 1 H), 4.40-4.34 (m, 1 H), 3.56-3.47 (m br, 2 H), 3.44-3.33 (m, 2 H), 1.33 (s, 3 H), 1.09 (s, 3 H), 1.07 (d, J = 6.9 Hz, 3 H), 1.05 (d, J = 6.9 Hz, 3 H), 0.92 (s, 3 H), 0.89 (s, 3 H), 0.81 (d, J = 6.1 Hz, 3 H), 0.79 (d, J = 6.1 Hz, 3 H). 13C NMR (100 MHz, DEPT, CDCl3): δ = 212.88 (s), 210.61 (s), 154.27 (s), 148.52 (s), 148.33 (s), 148.27 (s), 148.09 (s), 121.54 (d), 109.28 (s), 107.04 (s), 83.92 (d), 79.13 (d), 67.10 (t), 66.89 (t), 62.27 (s), 55.65 (d), 55.01 (s), 54.79 (d), 53.53 (d), 53.08 (d), 49.73 (d), 45.25 (t), 45.11 (t), 44.19 (d), 42.22 (d), 41.59 (d), 41.23 (d), 37.62 (t), 37.18 (t), 36.34 (s), 36.12 (s), 35.28 (t), 35.22 (t), 34.18 (d), 33.92 (d), 31.42 (t), 31.24 (t), 31.17 (2 t), 30.30 (d), 30.18 (d), 29.69 (t), 29.12 (t), 28.78 (t), 28.08 (t), 27.86 (t), 20.73 (q), 17.15 (q), 17.13 (q), 15.92 (q), 13.76 (q), 13.22 (q), 11.69 (q), 11.47 (q). MS-FAB (NBA matrix): m/z (%) = 846 (100)[M+], 828 (19), 732 (20), 154 (33) [NBA matrix].