Total Synthesis of 6-Amino-2,6-dideoxy-α-Kdo from d-Mannose

Org Lett. 2020 Aug 7;22(15):5783-5788. doi: 10.1021/acs.orglett.0c01847. Epub 2020 Jul 14.

Abstract

3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) biosynthetic pathway is a promising target in antibacterial drug discovery. Herein, we report the total synthesis of 6-amino-2,6-dideoxy-α-Kdo in 15 steps from d-mannose as a potential inhibitor of Kdo-processing enzymes. Key steps of the synthetic sequence involve a Horner-Wadsworth-Emmons reaction for the two-carbon chain homologation followed by either a 6-exo-trig Pd-catalyzed reductive cyclization or a tandem Staudinger/aza-Wittig reaction with concomitant α-iminoester reduction, enabling the α-stereoselective formation of the Kdo-like six-membered azacyclic ring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycosides / chemical synthesis
  • Glycosylation
  • Lipopolysaccharides / chemistry
  • Mannose / chemistry*
  • Molecular Structure
  • Sugar Acids / chemical synthesis*
  • Sugar Acids / chemistry

Substances

  • Glycosides
  • Lipopolysaccharides
  • Sugar Acids
  • 2-keto-3-deoxyoctonate
  • Mannose