One-Pot Multicomponent Synthesis of β-Acetamido Ketones Using BF3-Et2O as Catalyst
Keywords:
Antithrombotic activity, β-Acetamido KetoneAbstract
Starting from different ketones 1a-1f, aldehyde 2a-2g, and acetonitriles 3a-3d we synthesize some bioactive β- Acetamido carbonyl compounds 4a-4h. We also attempted to synthesize these compounds by using phenylacetone and deoxybenzoins in place of ketones to afford the products 4i-4j. 1H-NMR spectra are presented. On the basis of QSAR studies, some compounds were tested for their anti-thrombotic activity in mice. Compound 4f, 4h and 4j were found to exhibit less percentage protection.
References
Eibracht P, Schimdt J. Tandem Reaction Sequences under Hydroformylation Conditions: New Synthetic Applications of Transition Metal Catalysis. Chem Rev 1999; 99: 3329-66.
Ugi I. Recent progress in the chemistry of multicomponent reactions. Pure Appl Chem 2001; 73: 187-91.
Bagley MC, Cale JW, Bower. A new one-pot three-component condensation reaction for the synthesis of 2,3,4,6-tetrasubstituted pyridines. Chem Commun 2002; 1682-83.
Bora U, Saikia A, Boruah RC. A Novel Microwave-Mediated One-Pot Synthesis of Indolizines via a Three-Component Reaction. Org Lett 2003; 5: 435-38.
Weber L, The application of multicomponent reactions in drug discovery. Curr Med Chem 2002; 9: 1241-44.
Zhu J, Bienayme H. Multicomponent Reactions. Wiley: Weinheim 2005.
Beck B, Hess S, Domling A. One-pot Synthesis and Biological Evaluation of Aspergillamides and Analogues. Bioorg Med Chem Lett 2000; 10 (15): 1701-5.
Armstrong RW, Combs AP, Tempest PA, Brown SD, Keating TA. Multiple-Component Condensation Strategies for Combinatorial Library Synthesis. Acc Chem Res 1996; 29 (3): 123–131.
Terret NK, Gardner M, Gordon DW, Kobylecki RJ, Steel J. Combinatorial synthesis- the design of compound libraries and their application to drug discovery. Tetrahedron 1995; 51: 8135–8173.
Casimir JR, Turetta C, Ettouati L, Paris J. First application of the Dakin-West reaction to fmoc chemistry: Synthesis of the ketomethylene tripeptide fmoc-Nα-Asp(tBu)-(R,S Tyr(tBu)Ψ(CO-CH2)Gly-OH. Tetrahedron Lett 1995; 36: 4797-4800.
Godfrey AG, Brooks DA, Hay LA, Peters M, McCarthy JR, Mitchell D. Application of the Dakin−West Reaction for the Synthesis of Oxazole-Containing Dual PPARα/γ Agonists. J Org Chem 2003; 68: 2623–2632.
Dahn U, Hagenmaier H, Hohne H, Konig W.A, Wolf G, Zahner H. Metabolic Products of Microorganisms. Arch Microbiol 1976; 107: 143–160.
Ugi I, Werner B, Domling A. The Chemistry of Isocyanides, their Multicomponent Reactions and their Libraries. Molecules 2003; 8: 53-66.
Domling A. The discovery of new Isocyanide-based Multi-component Reactions. Curr Opin Chem Biol 2000; 4 (3): 318-23.
Weber L. Multi-component Reactions and Evolutionary Chemistry. Drug Discovery Today 2002; 7 (2): 143-47.
Zhu J, Bienayme H. Multicomponent Reactions. Wiley-VCH: Weinheim, Germany 2005.