Synthesis of the enantiomers of XYLNAc and LYXNAc: comparison of β-N-acetylhexosaminidase inhibition by the 8 stereoisomers of 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols

Org Biomol Chem. 2014 Jun 21;12(23):3932-43. doi: 10.1039/c4ob00097h.

Abstract

The enantiomers of XYLNAc (2-N-acetylamino-1,2,4-trideoxy-1,4-iminoxylitol) are prepared from the enantiomers of glucuronolactone; the synthesis of the enantiomers of LYXNAc (2-N-acetylamino-1,2,4-trideoxy-1,4-iminolyxitol) from an L-arabinono-δ-lactone and a D-ribono-δ-lactone is reported. A comparison is made of the inhibition of β-N-acetylhexosaminidases (HexNAcases) and α-N-acetylgalactosaminidase (α-GalNAcase) by 8 stereoisomeric 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols; their N-benzyl derivatives are better inhibitors than the parent compounds. Both XYLNAc and LABNAc are potent inhibitors against HexNAcases. None of the compounds show any inhibition of α-GalNAcase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Fabaceae / enzymology
  • Imines / chemistry*
  • Imines / pharmacology*
  • Pyrrolidines / chemistry
  • Stereoisomerism
  • Xylitol / analogs & derivatives*
  • Xylitol / chemical synthesis*
  • Xylitol / chemistry
  • beta-N-Acetylhexosaminidases / antagonists & inhibitors*
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • 2-N-acetylamino-1,2,4-trideoxy-1,4-iminolyxitol
  • 2-N-acetylamino-1,2,4-trideoxy-1,4-iminoxylitol
  • Enzyme Inhibitors
  • Imines
  • Pyrrolidines
  • beta-N-Acetylhexosaminidases
  • Xylitol