Synthesis and antiviral activity of purine 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl nucleosides.

9-(2',3'-Dideoxy-2',3'-difluoro-beta-D-arabinofuranosyl)adenine (20), 2-chloro-9-(2',3'-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)adenine (22), as well as their respective alpha-anomers 21 and 23, were synthesized by the nucleobase anion glycosylation of intermediate 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-alpha-D-arabinofuranosyl bromide (13) starting from methyl 5-O-benzyl-3-deoxy-3-fluoro-alpha-D-ribofuranoside (3) and methyl 5-O-benzoyl-alpha-D-xylofuranoside (10). These compounds were evaluated as potential inhibitors of HIV-1 and hepatitis C virus in human PBM and Huh-7 Replicon cells, respectively. The adenosine analog 20 demonstrated potent activity against HIV-1 in primary human lymphocytes with no apparent cytotoxicity. Conformation of pentofuranose ring of nucleoside 20 in solution was studied by PSEUROT calculations.