A Direct Synthesis for a New Series of 2‐Oxo(thioxo)nicotinonitrile Nucleosides as Antimicrobial Agents

A facile synthesis of a new series of cyclic and acyclic nucleosides of polyfunctionalized 2‐oxo(thioxo)nicotinonitrile derivatives 1 and 2 was performed. Glycosylation of 2‐pyridone 1 and 2‐thiopyridone 2 with glycosyl/galactosyl bromides in the existence of KOH afforded the N‐nucleoside and S‐nucleoside analogues 3, 5, 7, and 9, respectively. Deacetylation of nucleosides 3, 5, 7, and 9 gave the deacetylated nucleosides 4, 6, 8, and 10, respectively. Alkylation of 2‐pyridone 1 with glycone analogues [namely, 4‐bromobutyl acetate, (2‐acetoxyethoxy)methyl bromide, 3‐chloropropane‐1,2‐diol, and allyl and / propargyl bromides] in the existence of K2CO3 afforded the corresponding O‐acyclic nucleoside analogues 11, 13, and 15–17, respectively. Finally, treating of compounds 11 and 13 with a small amount of Et3N tolerated the 6‐hydroxy deacetylated derivatives 12 and 14, respectively. The synthesized nucleosides and alkylated products were tested against Gram (+ve) (Staphylococcus aureus and Bacillus cereus) and (Pseudomonas aeruginosa and Escherichia coli) as Gram (−ve) and Fungi (Aspergillus flavus and Aspergillus niger) and showed moderate antibacterial and antifungal activity.