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A Direct Synthesis for a New Series of 2‐Oxo(thioxo)nicotinonitrile Nucleosides as Antimicrobial Agents
Author(s) -
ElSayed Hassan A.,
ElTorky Alaa ElDin M. M.,
Moustafa Ahmed H.
Publication year - 2019
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.3394
Subject(s) - chemistry , bacillus cereus , aspergillus niger , aspergillus flavus , alkylation , bromide , antimicrobial , propargyl bromide , nucleoside , stereochemistry , organic chemistry , bacteria , catalysis , biochemistry , genetics , food science , biology
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 K 2 CO 3 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 Et 3 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.