Convergent Synthesis of Sialyl LewisX- O-Core-1 Threonine

J Org Chem. 2018 May 4;83(9):4963-4972. doi: 10.1021/acs.joc.7b03117. Epub 2018 Apr 23.

Abstract

Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl LewisX (sLeX) linked to a Core-1- O-hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using α-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chemistry Techniques, Synthetic
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / chemistry*
  • Sialyl Lewis X Antigen
  • Threonine / chemistry*

Substances

  • Oligosaccharides
  • Sialyl Lewis X Antigen
  • Threonine