The synthesis of the uridine 4ʹ,5ʹ-enol acetate 2a and its conversion to the unique anhydronucleoside 5a are described. The chemistry of 5a with regard to a variety of nucleophiles is examined. For example, treatment of 5a with methanol, ethanol, or ethylene glycol and AgN3O produced epimeric 4ʹ-alkoxy substituted nucleosides, isolated as the 5ʹ-hemiacetal (16a, 16d, 17a, 17d, 18). These hemiacetals were readily reduced with NaBH4to the corresponding alcohols (16c, 16f, 16g, 17c, 17f, 17g). Selective removal of the cyclohexylidene protecting group in the presence of the newly generated ketal at C4ʹwas possible under carefully controlled conditions utilizing aqueous trichloroacetic acid. © 1979, American Chemical Society. All rights reserved.