Synthesis and Biological Evaluation of Substituted Fused Dipyranoquinolinones

Abstract

New methyl-substituted, and diphenyl-substituted fused dipyranoquinolinones are prepared in excellent yields via the triple bond activation and 6-endo-dig cyclization of propargyloxycoumarin derivatives by gold nanoparticles supported on TiO2 in chlorobenzene under microwave irradiation. In the absence of gold nanoparticles, the methyl-substituted propargyloxycoumarin derivatives resulted in fused furopyranoquinolinones through Claisen rearrangement and 5-exo-dig cyclization. The intermediate propargyloxy-fused pyridocoumarins are prepared by propargylation of the corresponding hydroxy-fused pyridocoumarins. The methyl-substituted derivatives of the latter are synthesized in excellent yield by the three-component reaction of amino hydroxycoumarin with n-butyl vinyl ether under iodine catalysis. The diphenyl-substituted derivatives of hydroxy-fused pyridocoumarins are obtained, also, by the three-component reaction of amino hydroxycoumarin with benzaldehyde and phenyl acetylene catalyzed by iron (III) chloride. Preliminary biological tests of the title compounds indicated lipoxygenase (LOX) (EC 1.13.11.12) inhibitory activity (60–100 μM), whereas compound 28a, with IC50 = 10 μM, was found to be a potent LOX inhibitor and a possible lead compound. Only compounds 10b and 28b significantly inhibited lipid peroxidation.

Keywords

• fused dipyranoquinolinones
• fused pyridocoumarins
• iodine catalysis
• <i>n</i>-butyl vinyl ether
• Au-nanoparticles
• fused furopyranoquinolinones