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

Org Lett. 2019 Sep 6;21(17):6966-6971. doi: 10.1021/acs.orglett.9b02555. Epub 2019 Aug 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Crystallography, X-Ray
  • Cyclopropanes / chemical synthesis
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Respiratory Syncytial Virus, Human / drug effects*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Uridine / analogs & derivatives
  • Uridine / chemical synthesis
  • Uridine / pharmacology*

Substances

  • Antiviral Agents
  • Cyclopropanes
  • Spiro Compounds
  • cyclopropane
  • Uridine