Direct Synthesis of 2,6-Dideoxy-β-glycosides and β-Rhamnosides with a Stereodirecting 2-(Diphenylphosphinoyl)acetyl Group

Angew Chem Int Ed Engl. 2022 Aug 15;61(33):e202206128. doi: 10.1002/anie.202206128. Epub 2022 Jul 4.

Abstract

Anomeric stereocontrol is usually one of the major issues in the synthesis of complex carbohydrates, particularly those involving β-configured 2,6-dideoxyglycoside and d/l-rhamnoside moieties. Herein, we report that 2-(diphenylphosphinoyl)acetyl is highly effective as a remote stereodirecting group in the direct synthesis of these challenging β-glycosides under mild conditions. A deoxy-trisaccharide as a mimic of the sugar chain of landomycin E was prepared stereospecifically in high yield. The synthetic potential was also highlighted in the synthesis of Citrobacter freundii O-antigens composed of a [→4)-α-d-Manp-(1→3)-β-d-Rhap(1→4)-β-d-Rhap-(1→] repeating unit, wherein the convergent assembly up to a nonasaccharide was realized with a strongly β-directing trisaccharide donor. Variable-temperature NMR studies indicate the presence of intermolecular H-bonding between the donor and the bulky acceptor as direct spectral evidence in support of the concept of hydrogen-bond-mediated aglycone delivery.

Keywords: 2,6-Dideoxy-β-Glycosides; Diastereoselectivity; Glycosylation; Hydrogen Bonds; β-Rhamnosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Carbohydrates
  • Glycosides* / chemistry
  • O Antigens / chemistry
  • Oligosaccharides* / chemistry
  • Trisaccharides / chemistry

Substances

  • Carbohydrates
  • Glycosides
  • O Antigens
  • Oligosaccharides
  • Trisaccharides