Convergent synthesis of oligomannose-type glycans via step-economical construction of branch structures

Carbohydr Res. 2023 Mar:525:108764. doi: 10.1016/j.carres.2023.108764. Epub 2023 Feb 16.

Abstract

Oligomannose-type glycans on glycoproteins are important signaling molecules in the glycoprotein quality control system in the endoplasmic reticulum. Recently, free oligomannose-type glycans generated by the hydrolysis of glycoproteins or dolichol pyrophosphate-linked oligosaccharides were recognized as important signals for immunogenicity. Hence, there is a high demand for pure oligomannose-type glycans for biochemical experiments; however, the chemical synthesis of glycans to achieve high-concentration products is laborious. In this study, we demonstrate a simple and efficient synthetic strategy for oligomannose-type glycans. Sequential regioselective α-mannosylation at the C-3 and C-6 positions of 2,3,4,6-unprotected galactose residues in galactosylchitobiose derivatives was demonstrated. Subsequently, the inversion of the configuration of the two hydroxy groups at the C-2 and C-4 positions of the galactose moiety was successfully carried out. This synthetic route reduces the number of the protection-deprotection reactions and is suitable for constructing different branching patterns of oligomannose-type glycans, such as M9, M5A, and M5B.

Keywords: Chemical synthesis; Oligomannose-type N-Glycan; Regio/stereo-selective glycosylation; Self-coupling glycosylation.

MeSH terms

  • Galactose*
  • Glycoproteins / metabolism
  • Glycosylation
  • Oligosaccharides / chemistry
  • Polysaccharides* / chemistry

Substances

  • Galactose
  • Polysaccharides
  • Glycoproteins
  • Oligosaccharides