Synthesis and Biological Activity of Some Nucleoside Analogs of 3-Cyanopyridin-2- one

Hosam      A. Saad; Shams      H. Abdel-Hafez

Abstract

The pyridine derivative 3-cyano-4-(4-isopropylphenyl)-6-(pyridin-2-yl)-1H-pyridine-2-one 1 was obtained via the reaction of 2-acetylpyridine with cuminaldehyde and ethyl cyanoacetate in the presence of ammonium acetate. The pyridine-2-one 1 reacted with different alkyl halides, namely, allyl bromide, propargyl bromide, methyl bromoacetate, epichlorohydrin, 3-chloro-1-propanol, 1,3- dichloro-2-propanol, 4-bromobutyl acetate and 2-(bromomethoxy)ethyl acetate to give the corresponding nicotinonitrile Oacyclonucleosides 2-9 and 11, respectively. Subsequently, 9 and 11 were deacetylated to give the corresponding deprotected acyclonucleosides 10 and 12, respectively. In contrast, 4-(4-isopropylphenyl)-2-(2',3',4',6'-tetra-O-acetyl-β-D-gluco(galacto)pyranosyloxy)-6- (pyridin-2-yl)nicotinonitrile 13, 14, riboside 17 and lactoside 19 were prepared by the reaction of 1 with glycosyl/galactosyl/lactosyl bromide and peracetylated ribose using conventional and microwave irradiation methods. The reaction was regioselective and yielded the O-glycosides instead of the expected N-glycosides. The glycosides 13 and 14, riboside 17, and lactoside 19 were deacetylated in the presence of Et3N/MeOH and a few drops of water to give 15, 16, 18 and 21, respectively. The structure of the newly synthesized compounds was confirmed using IR, 1H and 13C NMR spectra, mass spectra and microanalysis. All synthesized compounds showed high antibacterial activity but the antifungal activity shown only by the glycoside compounds. Also, some of the new compounds showed anticancer activities.

Keywords: Pyridin-2(1H)-one, acyclonucleosides, cuminaldehyde, glycosides, riboside, lactoside, anticancer and antibacterial

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