Resolution of enantiomers of uridine analogs, potential antiviral agents

Racemic mixtures of 5-substituted carbocylic analogs of uracil nucleosides, 2 ''- and 3 ''-furyl, 2 ''- and 3 ''-thienyl and 2 ''-selenienyl, potentially anti-viral agents, were resolved using amylose tris(3,5-dimethylphenyl)carbamate as the stationary phase. The mobile phase was n-hexane with ethanol or 2-propanol. Effects of some structural features on the extent of discrimination between the enantiomers were examined through the selectivity and resolution factors as well as the elution order. The structural features were as follows; the type and position of the hetero-atom O, S or Se, in the cyclopentadienyl substituent 5 of the uracil and hydroxymethyl vs. acetoxymethyl groups on the cyclopentene moiety of the uridine analogs. It appeared that effects of the structural features on the separation were solvent dependent, with some very unusual solvent effects. For example, average retention, which did not follow the polarity of the mobile phase modifiers, was much higher when ethanol was used compared to 2-propanol. Also, the elution order of the two enantiomers of several pairs was reversed when ethanol was changed to 2-propanol. In general, ethanol affected higher selectivity and resolution of all the enantiomeric pairs.