Synthesis, antitumor and antimicrobial activities of 4-(4-chlorophenyl)-3-cyano-2-(β-O-glycosyloxy)-6-(thien-2-yl)-nicotinonitrile

4-(4-Chlorophenyl)-3-cyano-6-(thien-2-yl)-1H-pyridin-2-one (2) was obtained by reaction of 2-acetyl thiophene with 4-chlorobenzaldehyde and ethyl cyanoacetate in presence of ammonium acetate or by the reaction of α,β-unsaturated compound 1 with ethyl cyanoacetate in the presence of ammonium acetate. 4-(4-Chlorophenyl)-2-(2′,3′,4′,6′-tetra-O-acetyl-β-d-gluco/galactopyranosyloxy)-6-(thien-2-yl)nicotinonitrile (5a and 5b), riboside 11, xyloside 12 and lactoside 16 were prepared by the reaction of 2 with glycosyl/galactosyl/xylosyl/lactosyl bromide and peracetylated xylose/ribose under the conventional and microwave irradiation methods. The reaction has regioselectively gave the O-glycosides and not the N-glycosides. The glycosides 5a,b, riboside 11, xyloside 12 and lactoside 16 were deacetylated in the presence of Et3N/MeOH and few drops of water to give 7a,b, 13, 14 and 17. The structure of the new synthesized compounds was confirmed by using IR, 1H, 13C NMR spectra and microanalysis. Selected members of these compounds were screened for antitumor and antibacterial activity.

Graphical abstractGlycosylation of 3-cyanopyridin-2(1H)-one 2 gave the 2-O-glycosyloxy and not the N-glycosyl analogs as acetyl derivatives whose deacetylation gave the target compounds. These were screened for the antitumor and antimicrobial activities.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The synthesis of 2-O-glycosyl nicotinonitrile derivatives is reported. ► These glycosides possess good antimicrobial activity. ► Compounds 12 and 5b showed antibacterial activity and moderate antitumor activity against (MCF7) cell line.