Synthesis of acyclic 6,7-dihaloquinolone nucleoside analogues as potential antibacterial and antiviral agents.
Reaction of the quinolone carboxylic acids 1 and 2 with (2-acetoxyethoxy)methyl chloride 3 in the presence of n-Bu4NI afforded the N-alkylated products 4 and 6, which could be deblocked to the free nucleoside analogues 5 and 7, respectively. The alkylated quinolone carboxylic acids 9 and 10 were obtained by condensation of I and 2 with 1,4-dichlorobut-2-ene 8 in the presence of NaH. Hydrolysis of 9 gave the alcohol 11. Similar treatment of 1 with 8 in the presence of K2CO3 at relatively high temperature furnished 12. Prolonged heating of the ester 13 with 8 in NaH/DMF afforded the conjugated-diene 15. Treatment of 1 and 2 with dimethyl acetylenedicarboxylate 16 furnished the pyrano[4,3-b]quinolones 17 and 18, respectively. Antibacterial and antiviral evaluations of the new products are reported.
Al-Masoudi
N A
NA
Faculty of Chemistry, University of Konstanz, Germany. masoudi@chclu.chemie.uni-konstanz.de
Al-Soud
Y A
YA
Eherman
M
M
De Clercq
E
E
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry*; D013057:Spectrum Analysis
D000890:Anti-Infective Agents; D000998:Antiviral Agents; D009705:Nucleosides; D015363:Quinolones