Substituted benzimidazoles: antiviral activity and synthesis of nucleosides

Abstract

The antiviral activity of a series of benzimidazole derivatives and substituted benzimidazole beta-L- and beta-D-2'-deoxyribonucleosides against selected RNA and DNA viruses including HIV-1, BVDV, YFV, DENV-2, WNV, HBV, HCV and human RSV was evaluated. In addition, the synthesis of several benzimidazole beta-L-2'-deoxyribonucleosides (1-4) and 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl nucleoside 5 is described. The stereoselective glycosylation of the anions of the functionalized benzimidazoles 6a, 12a and 28 with 3,5-di-O-(4-methylbenzoyl)-2-deoxy-alpha-L-erythro-pentofuranosyl chloride (29) furnished beta-L-2'-deoxyribonucleosides 1-4 while the glycosylation of the anion of 2-bromobenzimidazole (12a) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide 34 gave the 2'-deoxy-2-fluoro-beta-D-arabinofuranosyl nucleoside 5. Moreover, the crystal structure of the benzoylated 2-bromobenzimidazole 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl nucleoside 35 is reported.