The synthesis of a series of deoxygenated 2,3-difluoro-N-acteylneuraminic acid derivatives as potential sialidase inhibitors

Carbohydr Res. 2013 Jun 7:374:23-8. doi: 10.1016/j.carres.2013.03.026. Epub 2013 Apr 2.

Abstract

Here we describe the successful syntheses of a series of 4-, 7-, 8- and 9-deoxygenated 2,3-difluoro-N-acetylneuraminic acid derivatives as potential mechanism-based inhibitors of sialidases. The syntheses commenced utilising an enzyme-catalysed aldolase reaction between N-acetyl mannosamine and β-fluoropyruvic acid to give 3-fluoro-N-acetyl-neuraminic acid. This common intermediate was then used in selective protection protocols and Barton-McCombie deoxygenations to generate the complete set of mono-deoxygenated 3-fluoro-N-acetylneuraminic acid derivatives. Finally, a fluorination step utilising (diethylamino)sulfur trifluoride (DAST) was used to successfully generate each of the target difluorides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Oxygen / chemistry*
  • Sialic Acids / chemical synthesis
  • Sialic Acids / chemistry
  • Sialic Acids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Sialic Acids
  • Neuraminidase
  • Oxygen