Stereochemical Aspects of the anti-HCMV Activity of Cytidine Nucleoside Analogues

The remarkable selectivity of the β-L enantiomers of 2′,3′-dideoxycytidine analogues against the viral polymerases of HIV and HBV has stimulated our interest in targeting β-L enantiomers of anti-HCMV cytidine analogues. Indeed, Ara-C, FIAC and DMDC are cytidine analogues with β-D configuration that show significant potency as anti-HCMV agents but lack selectivity. β-L enantiomers have therefore been synthesized and evaluated together with four other nucleoside analogues, and the β-L. enantiomers were found not to be inhibitory to HCMV replication. However, the three α-L isomers, α-L-Ara-C, α-L-Xylo-C and α-L-FMAU, emerged with activity against HCMV and have provided new approaches for the treatment of viral diseases with nucleoside analogues possessing the unusual L-configuration.