Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxylysine and incorporation in a glycopeptide from type II collagen

J Org Chem. 2006 Mar 3;71(5):1911-9. doi: 10.1021/jo052256z.

Abstract

A stereoselective synthesis of the C-glycoside analogue of beta-D-galactosyl-(5R,2S)-hydroxylysine (1) has been achieved starting from tetra-O-benzyl-D-galactopyranosyl lactone. The synthesis involved establishment of three stereogenic centers in an unambiguous manner. A facially selective Grignard reaction followed by a silane reduction was used for the anomeric position of the C-galactose residue. An Evans allylation established the configuration of the delta-aminomethylene group of the hydroxylysine moiety, whereas an asymmetric hydrogenation utilizing Burk's catalyst was used for the alpha-amino acid moiety itself. The synthesis was completed in 17 steps with an overall yield of 18%, resulting in the most complex and functionalized C-glycoside analogue of a naturally occurring glycosylated amino acid prepared to date. In addition, amino acid 1 was incorporated in a glycopeptide from type II collagen known to be crucial for the response of autoimmune T cells obtained in models of rheumatoid arthritis. A preliminary immunological study revealed that four out of five members in a panel of T cell hybridomas were able to recognize this C-linked glycopeptide when presented by A(q) class II MHC molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis
  • Animals
  • Collagen Type II / chemistry*
  • Glycopeptides / chemical synthesis
  • Glycopeptides / chemistry*
  • Glycopeptides / pharmacology
  • Glycosides
  • Hybridomas / drug effects
  • Hydroxylysine / analogs & derivatives*
  • Hydroxylysine / chemical synthesis
  • Mice
  • Monosaccharides / chemistry*
  • T-Lymphocytes / drug effects

Substances

  • Amino Acids
  • C-glycoside
  • Collagen Type II
  • Glycopeptides
  • Glycosides
  • Monosaccharides
  • Hydroxylysine
  • galactosylhydroxylysine