Total Synthesis and Biological Evaluation of the Glycosylated Macrocyclic Antibiotic Mangrolide A

Angew Chem Int Ed Engl. 2018 Aug 20;57(34):11020-11024. doi: 10.1002/anie.201805770. Epub 2018 Jul 18.

Abstract

The macrocyclic antibiotic mangrolide A has been described to exhibit potent activity against a number of clinically important Gram-negative pathogens. Reported is the first enantioselective total synthesis of mangrolide A and derivatives. Salient features of this synthesis include a highly convergent macrocycle preparation, stereoselective synthesis of the disaccharide moiety, and two β-selective glycosylations. The synthesis of mangrolide A and its analogues enabled the re-examination of its activity against bacterial pathogens, and only minimal activity was observed.

Keywords: antibiotics; carbohydrates; glycosylation; natural products; total synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Carbohydrate Sequence
  • Drug Resistance, Bacterial
  • Glycosylation
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Macrocyclic Compounds / chemical synthesis*
  • Macrocyclic Compounds / chemistry
  • Macrocyclic Compounds / pharmacology*
  • Microbial Sensitivity Tests
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Macrocyclic Compounds