Análise conformacional de compostos de Biginelli com atividade antineoplásica

Abstract : .Dihydropyrimidinones, such as monastrol and analogues, are heterocycles with known antineoplastic activity. Conformational analysis represents an important preliminary step in structure-activity correlation studies. Herein we describe the conformational analysis of monastrol and analogues by AM1 semi-empirical and ab initio HF/6-31G* calculations. Four equilibrium geometries were found ( s-cis/ap, s-cis/sp, s-trans/ap and s-trans/sp) , and the important internal rotations were those of the ab-unsaturated carbonyl system and of the aryl group connected to the heterocycle Keywords: conformational analysis, dihydropyrimidinones, Biginelli compound, AM1, HF/6-31G* Referencias [1] C. O. Kappe, Eur. J. Med. Chem. 35(12) (2000) 1043. [2] B. Desai, D. Dallinger, C. O. Kappe, Tetrahedron 62 (2006) 4651. [3] C. O. Kappe, O. V. Shishkin, G. Uray, P. Verdino Tetrahedron 56 (2000) 1859. [4] D. Russowsky, R. F. S. Canto, S. A. A. Sanches, M. G. M. D´Oca, A.Fatima, R. A. Pilli, L. K. Kohn, M. A. Antonio, J. E. Carvalho, Bioorg. Chem. 34 (2006) 173. [5] E. L. Eliel, S.H. Wilen, Stereochemistry of Organic Compounds, Wiley, New York, 1994.[6] C.R. Rodrigues, Cadernos Tematicos Quim. Nova Esc. 3 (2001) 43.[7] C. O. Kappe, W . M. F Fabian, A. Semones, Tetrahedron 53 (1997) 2803. [8] M.J.S. Dewar , E.G. Zoebisch, E.F . Healy J.J.P Stewart, J. Am. Chem. Soc. 107(13) (1985) 3902. [9] Spartan´02 (1.0.1), Wavefunction: Irvine, 2002.[10] G. D. Smith, R. L. Jaffe, J. Phys. Chem. 100 (48) (1996) 18718.M. J. Hafezi, F. Sharif, Mol. Struct.: THEOCHEM 814(1-3) (2007) 43.