A Direct Synthesis for a New Series of 2‐Oxo(thioxo)nicotinonitrile Nucleosides as Antimicrobial Agents. (26th November 2018)

• Record Type: Journal Article
• Authors: El‐Sayed, Hassan A.; El‐Torky, Alaa El‐Din M. M.; Moustafa, Ahmed H.
• Is Part Of: Journal of heterocyclic chemistry. Volume 56:Number 1(2019)
• Page Start: 188
• Page End: 194
• Publication Date: 2018-11-26
• Subjects: Heterocyclic compounds -- Periodicals; 547.59
• DOI: 10.1002/jhet.3394
• Languages: English
• ISSNs: 0022-152X

Abstract

Abstract : 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 K2 CO3 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 Et3 N 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. Abstract :