Microwave-assisted synthesis of 4?-azaflavones and their n-alkyl derivatives with biological activities

Abstract

4?-Azaflavone (=2-(pyridin-4-yl)-4H-1-benzopyran-4-one; 4) and 3-[(pyridin-4-yl)methyl]-4?-azaflavone (5) were synthesized by a simple environmentally friendly microwave-assisted one-pot method through the cyclization of 3-hydroxy-1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propan-1-one (1), (E)-2?-hydroxy-4-azachalcone (2; chalcone=1,3-diphenylprop-2-en-1-one), and 2?-hydroxy-2-[(hydroxy)(pyridin-4-yl)methyl]-4?-azachalcone (3) under solventless conditions using silica-supported NaHSO4, followed by treatment with base. In addition, N-alkyl-substituted 4?-azaflavonium bromides 6 and 7 were prepared from compounds 4 and 5, respectively. The antimicrobial and antioxidant activities of compounds 1-7 were tested. The N-alkyl-substituted 4?-azaflavonium bromides 6 and 7 showed high antimicrobial activity against the Gram-positive bacteria and the fungus tested, with MIC values close to those of reference antimicrobials ampicilline and fluconazole. The alkylated compounds 6 and 7 also showed a good antioxidant character in the two antioxidant methods, DPPH (=1,1-diphenyl-2-picrylhydrazyl) radical-scavenging and ferric reducing/ antioxidant power (FRAP) tests. © 2008 Verlag Helvetica Chimica Acta AG, Zürich.