Synthesis of a C-Glycoside Analogue of -D-Galactosyl Hydroxylysine and Incorporation in a Glycopeptide from Type II Collagen
2006 (English)In: Journal of Organic Chemistry, Vol. 71, no 5, 1911-9 p.Article in journal (Refereed) Published
A stereoselective synthesis of the C-glycoside analogue of -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 -aminomethylene group of the hydroxylysine moiety, whereas an asymmetric hydrogenation utilizing Burk's catalyst was used for the -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 Aq class II MHC molecules.
Place, publisher, year, edition, pages
2006. Vol. 71, no 5, 1911-9 p.
IdentifiersURN: urn:nbn:se:umu:diva-16100DOI: doi:10.1021/jo052256zOAI: oai:DiVA.org:umu-16100DiVA: diva2:155773