A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin 'in-chloride'

Bioorg Med Chem Lett. 2016 Feb 1;26(3):1025-1028. doi: 10.1016/j.bmcl.2015.12.027. Epub 2015 Dec 11.

Abstract

In an effort to rapidly access vancomycin analogues bearing diverse functionality at the 6c-Cl (the 'in-chloride') position, a two-step dechlorination/cross-coupling protocol was developed. Conditions for efficient cross-coupling of the relatively unreactive 6c-Cl group were found that ensure high conversion with minimal product decomposition. A set of 2c-dechloro-6c-functionalized vancomycin derivatives was prepared, and antibiotic activities of the compounds were evaluated against a panel of vancomycin-resistant and vancomycin-susceptible strains. Results from biological testing further underscore the steric sensitivity of vancomycin's binding pocket.

Keywords: Cross-coupling; Vancomycin; Vancomycin analogues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Boronic Acids / chemistry
  • Catalysis
  • Chlorides / chemistry*
  • Halogenation
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects
  • Vancomycin / analogs & derivatives*
  • Vancomycin / chemical synthesis
  • Vancomycin / pharmacology
  • Vancomycin Resistance / drug effects

Substances

  • Anti-Bacterial Agents
  • Boronic Acids
  • Chlorides
  • Vancomycin