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

The Journal of Organic Chemistry: Volume 85, Issue 6, Page 4267-4278

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.

DOI: 10.1021/acs.joc.9b03425