Synthesis and mannosidase inhibitory profile of a small library of aminocyclitols from shikimic acid-derived scaffolds

Carbohydr Res. 2020 Jul:493:108027. doi: 10.1016/j.carres.2020.108027. Epub 2020 May 11.

Abstract

A short synthetic route to a small library of aminocyclitols 14·HCl-19·HCl has been elaborated from the common shikimic acid-derived scaffolds 20 and 21. The developed strategy features three oxidative processes ‒ ozonolysis, dihydroxylation and epoxidation ‒ as the key transformations. The stereochemistry of the newly created stereocentres was confirmed either via crystallographic analysis or by means of NOESY experiments conducted on advanced intermediates. Glycosidase inhibition study revealed no glucosidase inhibition and only weak inhibitory activity against recombinant Drosophila melanogaster Golgi mannosidase (GMIIb).

Keywords: Aminocyclitols; Dihydroxylation; Epoxidation; Glycosidase activity; Stereoselective synthesis.

MeSH terms

  • Carbohydrate Conformation
  • Cyclitols / chemical synthesis
  • Cyclitols / chemistry
  • Cyclitols / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Mannosidases / antagonists & inhibitors*
  • Mannosidases / metabolism
  • Shikimic Acid / analogs & derivatives
  • Shikimic Acid / chemistry*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • Cyclitols
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Shikimic Acid
  • Mannosidases