Enantiomeric synthesis of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus

Enantiomeric synthesis Of D- and L-cyclopentenyl nucleosides and their anti viral activity against HIV and West Nile virus are described. The key inter mediate (-)- and (+)-cyclopentenyl alcohols (7 and 15) were prepared from D -gamma -ribonolactone and D-ribose, respectively. Coupling of 7 with approp riately blocked purine and pyrimidine bases via the Mitsunobu reaction foll owed by deprotection afforded the target L-(+)-cyclopentenyl nucleosides (2 4-28, 31, 33, and 36). D-(-)Cyclopentenyl nucleosides (1, 40, 43, and 52-56 ) were also prepared by a similar procedure for L-isomers from 15. The synt hesized compounds were evaluated for their antiviral activity against two R NA viruses: HIV and West Nile virus. Among the synthesized D-(-)-nucleoside s, adenine (1, neplanocin A), cytosine (55, CPE-C), and 5-fluorocytosine (5 6) analogues exhibited moderate to potent anti-HIV activity (EC50 0.1, 0.06 , and 5.34 muM, respectively) with significant cytotoxicity in PBM, Vero, a nd CEM cells. Also, cytosine (55) and 5-fluorocytosine (56) analogues exhib ited the most potent anti-West Nile virus activity (EC50 0.2-3.0 and 15-20 muM, respectively). Among L-(+)-nucleosides, only the cytosine (27) analogu e exhibited weak anti-HIV activity (EC50 58.9 muM).