Synthesis of and characterization of differentially sulfated disaccharide repeating units of keratan sulfate

Keratan sulfate (KS) is a member of a broad family of sulfated polysaccharides known as glycosaminoglycans. Synthetic KS derivatives can lead to the advancement in early detection of mucopolysaccharidoses disorders using mass spectrometry. Reported herein is the synthesis of all four differentially sulfated keratan sulfate disaccharide repeat units. The efficient synthetic strategies to obtain non-sulfated, two different monosulfated, and disulfated derivatives has been developed. In accordance with our retrosynthetic analysis, all backbone disaccharide intermediates were synthesized from unique glycosyl donors and the universal glycosyl acceptor. Final purification of target compounds was accomplished by size exclusion chromatography, and all compounds were thoroughly characterized.