Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxylysine and incorporation in a glycopeptide from type II collagen.
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.
Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Tomas
T
Gustafsson
Mattias
M
Hedenström
Jan
J
Kihlberg
D000596:Amino Acids / Q000138:chemical synthesis; D000818:Animals; D024043:Collagen Type II / Q000737:chemistry*; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006027:Glycosides; D006825:Hybridomas / Q000187:drug effects; D006901:Hydroxylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D051379:Mice; D009005:Monosaccharides / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects
D000596:Amino Acids; C438934:C-glycoside; D024043:Collagen Type II; D006020:Glycopeptides; D006027:Glycosides; D009005:Monosaccharides; D006901:Hydroxylysine; C007817:galactosylhydroxylysine