The Nargenicin Family of Oxa-Bridged Macrolide Antibiotics

Chemistry. 2020 Mar 2;26(13):2780-2792. doi: 10.1002/chem.201904053. Epub 2019 Dec 16.


The nargenicin family of antibiotic macrolides comprise a group of bacterial natural products with a rare ether bridged cis-decalin moiety and a narrow spectrum of activity. Most family members were identified almost four decades ago and were placed on the shelf due to the numbers of broad-spectrum compounds available at the time. However, in light of rising rates of antimicrobial resistance, there has been a renewed interest in the use of narrow-spectrum antimicrobials. Here, we review the history of this family of compounds, including synthetic approaches, and highlight the recently uncovered genetic basis for nargenicin production. Given the renewed pharmaceutical interest in these compounds, we also investigate structure-activity relationships among these molecules, with a view to the future development of members of this unusual antibiotic family.

Keywords: biological activity; ether bridge; macrolide antibiotics; nargenicin; polyketides.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology*
  • Humans
  • Lactones / chemistry*
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Naphthalenes
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Bridged-Ring Compounds
  • Lactones
  • Macrolides
  • Naphthalenes
  • decalin