Efficient total syntheses and biological activities of two teixobactin analogues

Chem Commun (Camb). 2016 Apr 26;52(36):6060-3. doi: 10.1039/c5cc10249a.

Abstract

The discovery of the new antibiotic teixobactin has been timely in the race for unearthing novel antibiotics wherein the emergence of drug resistant bacteria poses a serious threat worldwide. Herein, we present the total syntheses and biological activities of two teixobactin analogues. This approach is simple, efficient and has several advantages: it uses commercially available building blocks (except AllocHN-d-Thr-OH), has a single purification step and a good recovery (22%). By using this approach we have synthesised two teixobactin analogues and established that the d-amino acids are critical for the antimicrobial activity of these analogues. With continuing high expectations from teixobactin, this work can be regarded as a stepping stone towards an in depth study of teixobactin, its analogues and the quest for synthesising similar molecules.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Depsipeptides / chemical synthesis*
  • Depsipeptides / pharmacology*
  • Escherichia coli / drug effects*
  • Escherichia coli Infections / drug therapy
  • Humans
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Depsipeptides
  • teixobactin