Protecting-Group-Mediated Diastereoselective Synthesis of C4′-Methylated Uridine Analogs and Their Activity against the Human Respiratory Syncytial Virus

Adjusting the protecting group strategy, from an alkyl ether to
a bidentate ketal at the carbohydrate backbone of uridine, facilitates
a switchable diastereoselective α- or β-C4′/C5′-spirocyclopropanation.
Using these spirocyclopropanated nucleosides as key intermediates,
we synthesized a variety of C4′-methylated d-ribose
and l-lyxose-configured uridine derivatives by a base-mediated
ring-opening of the spirocyclopropanol moiety. Investigations of antiviral
activity against the human respiratory syncytial virus were carried
out for selected derivatives, showing moderate activity.