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Electronic Conference on Heterocyclic Chemistry,, June 29 - July 24, 1998

Synthesis of 1-Alkyl- and 1-Alkylidene Substituted 3-Oxo-carbo- and Heterocycles with Potential Biological Activity

Wolfgang STADLBAUER, A. Elisabeth TÄUBL and Bernd KNOBLOCH

Institute of Organic Chemistry, Karl-Franzens University Graz, Austria

In this communication some new synthetic pathways to pharmacologically interesting target molecules are described. Carbo- and heterocyclic 1,3-dioxo compounds 1 having as basic ring system a pyridine, pyrane, quinoline, coumarin or phenalenone nucleus, give the reactive 1-chloro-3-oxo intermediates 2, which can be alkylated with CH-acidic compounds such as malonates if the substuent R1 has electron acceptor properties . Alkyl derivatives 3 have been shown in some cases (e.g. as 4-alkyl-2-pyridones) to possess antiviral activity [1].

The thermolytic degradation of ethyl malonates of type 3 gives the ethyl acetates 4. With the 2-quinolone ring system this class of compounds shows manifold pharmacological activities [2].

Methyl malonates 3 having as substituent R1 a nitro group form under thermolytic conditions by loss of carbon dioxide and methanol isoxazoles of type 7. The thermolysis reactions to 4 and 7 have been studied by differential scanning calorimetry (DSC) [3].

The Wittig- or Grignard reaction of 2,2-disubstituted 1,3-dicarbonyl carbo- or heterocycles 5 with alkyl-triphenylphosphonium halides leads to 1-alkylidene-3-oxo compounds 6. This compound class was recently found to show antiviral activities [4].

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Formula scheme


[1] V. Dolle, C. H. Nguyen, E. Bisagni, Tetrahedron 53 (1997) 12505.

[2] Z. Y. Jiang, Q.-L. Zhou, J. W. Eaton, W. H. Koppenol, J. V. Hunt, S. P. Wolff, Biochem. Pharmacol. 42, (1991) 1273; W. Carling, P. D. Leeson, K. W. Moore, M. Rowley (Merck, Sharp and Dohme Ltd), PCT Int. Appl. 93 11, 114 (1993).

[3] Th. Kappe and W. Stadlbauer, Molecules 1 (1996) 255.

[4] R. Kirsch, J. P. Kleim, G. Riess, M. Rösner, I. Winkler (Hoechst AG), Eur. Pat. EP 0 697 405 A1 (1996).

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