Imidazo(1,2-c)pyrimidine nucleosides. Synthesis and biological evaluation of certain 1-(beta-D-arabinofuranosyl)imidazo(1,2-c)pyrimidines.
The first chemical syntheses of the arabinosylhypoxanthine and arabinosylguanine analogues of the imidazo-[1,2-c]pyrimsdine series are described. Condensation of trimethylsilyl-7-chloroimidazo[1,2-c]pyrimidin-5-one (1) with 2,3,5-tri-O-benzyl-alpha-D-arabinofuranosyl chloride (2) gave 7-chloro-1-(2,3,5-tri-O-benzyl-beta-arabinofuranosyl)imidazo[1,2-c]pyrimidin-5-one (3) which on catalytic dehalogenation furnished 1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)imidazo[1,2-c]pyrimidin-5-one (4). Amination of 3 gave 7-amino-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)imidazo[1,2-c]pyrimidin-5-one (5). Reductive hydrogenolysis of 4 and 5 gave 1-(betaD-arabinofuranosyl)imidazo[1,2-c]pyrimidin-5-one (6), the arabinosylhypoxantine analogue, and the corresponding 7-amino isomer 7, the arabinoosylguanine analogue, respectively. The unequivocal assignment of the site of glycosylation and the anomeric configuration have been established. None of the compounds exhibited significant antiviral or antimicrobial activity in vitro.
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D001089:Arabinose / Q000138:chemical synthesis / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011513:Proteus mirabilis / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D014249:Trichophyton / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000998:Antiviral Agents; D007093:Imidazoles; D011741:Pyrimidine Nucleosides; D001089:Arabinose