Streamlined Access to Peptidoglycan Biosynthesis Terminator GlcNAc-1,6-anhydro-MurNAc

Org Lett. 2025 Jan 17;27(2):698-703. doi: 10.1021/acs.orglett.4c04620. Epub 2025 Jan 6.

Abstract

GlcNAc-1,6-anhydro-MurNAc is a key peptidoglycan elongation terminator of biological and medicinal importance. Herein, we present a concise approach to this molecule in 12 steps with an overall 25% yield using d-glucosamine as the sole starting material. Our synthesis features the formation of a 1,6-anhydro-MurNAc building block by an intramolecular glycosylation and the selective conversion of the phthalimido group of the MurNPhth moiety, paving the way for antibiotics with a new killing mechanism by targeting bacterial transglycosylase.

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Glucosamine / analogs & derivatives
  • Glucosamine / chemistry
  • Glycosylation
  • Molecular Structure
  • Muramic Acids / chemistry
  • Muramic Acids / metabolism
  • Peptidoglycan* / biosynthesis
  • Peptidoglycan* / chemistry

Substances

  • Peptidoglycan
  • Muramic Acids
  • Anti-Bacterial Agents
  • Glucosamine