Synthesis and Biological Evaluation of Some Acyclic Pyridine C-Nucleosides. Part One

Abstract The reaction between 3-bromo-5-chloromethylpyridine hydrochloride (4) with the mono sodium salt of ethylene glycol was investigated. 3-Bromo-5-(2-hydroxyethoxymethyl)-pyridine (5) was synthesized and converted to the 3-carboxy analogue using butyllithium and CO2. Subsequent treatment with diazomethane and ammonolysis gave the corresponding acyclic nicotinamide C-nucleosides. The latter compounds were converted into the thioamide analogues by reaction with Lawesson's reagent. The pyridine N-oxide derivatives were obtained by treatment with peracetic acid or hydrogen peroxide. All compounds were identified with the aid of 1H- and 13C-NMR and mass spectrometry. The acyclic pyridine C-nucleosides were evaluated against a number of viral strains and cancer cell lines but no significant biological activity was found.