Stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), a new potent hexosaminidase inhibitor

Org Lett. 2013 Jul 19;15(14):3638-41. doi: 10.1021/ol401517x. Epub 2013 Jun 26.

Abstract

A practical synthesis of the previously unreported N-acetyl-D-allosamine glycomimetic DAJNAc is described. The reaction sequence involves Pd-catalyzed allylic substitution by phthalimide in an azaheterobicyclic scaffold as the key step. The new iminosugar resulted in being a stronger β-N-acetylglucosaminidase (human placenta) competitive inhibitor than the D-gluco (DNJNAc) and D-galacto (DGJNAc) stereoisomers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / chemical synthesis
  • 1-Deoxynojirimycin / chemistry
  • Female
  • Hexosaminidases / analysis*
  • Hexosaminidases / chemistry*
  • Humans
  • Pregnancy
  • Stereoisomerism
  • beta-N-Acetylhexosaminidases / chemical synthesis*
  • beta-N-Acetylhexosaminidases / chemistry*

Substances

  • 2-acetamido-1,2-dideoxyallonojirimycin
  • 1-Deoxynojirimycin
  • Hexosaminidases
  • beta-N-Acetylhexosaminidases