Synthesis of 4′/5′-Spirocyclopropanated Uridine and d‑Xylouridine Derivatives and Their Activity against the Human Respiratory Syncytial Virus

The Simmons–Smith–Furukawa reaction was used to generate 4′/5′-spirocyclopropanated uridine analogs from electron-rich exocyclic enol esters. During synthesis, the native hydroxylation pattern of the nucleoside is preserved and offers the possibility for a late stage 5′-phosphorylation at the spirocyclopropanol moiety. All synthesized spirocyclopropanated uridine derivatives, including the corresponding 5′-monophosphate (cpUMP), were evaluated with respect to their antiviral activity in an HRSV assay showing moderate, but promising activity.