Solid-phase synthesis of the B-chain of human α2HS glycoprotein

The B-chain of human α2HS glycoprotein 1, a heptacosapeptide carrying a trisaccharide (sialyl T) side chain, was synthesized. Prior to the Fmoc-based solid-phase synthesis of the glycopeptide, the benzyl-protected glycosyl serine building block 6 was prepared via β-stereoselective glycosylation of the 2-azido-2-deoxygalactosyl serine 11 with the sialyl galactosyl trichloroacetimidate 9. An automated peptide synthesizer was efficiently used for the elongation of the entire peptide chain except for the coupling with 6. The synthesized glycopeptide was cleaved from the resin by the TFA method. The resultant mixture of the benzylated glycopeptides was treated with TMSOTf–thioanisole in TFA and then with aq NaHCO3 and 1,4-dithiothreitol to give 1.