Convenient synthesis of Thr and Ser carrying the tumor associated sialyl-(2→3)-T antigen as building blocks for solid-phase glycopeptide synthesis

Abstract

Sialyl-T antigens have been synthesized, conveniently and in high yield, by a block condensation approach. Glycosylation of the D-GalN₃ derivative with the suitably protected sialyl-α-(2→3)-D-galactopyranosyl trichloroacetimidate by using trimethylsilyl trifluoromethanesulfonate (TMS-OTf) as a promoter in dichloromethane gave the trisaccharide in high yield. Cleavage of the tert-butyldimethylsilyl ether (TBDMS) at the anomeric position of the sialic acid containing trisaccharide derivative, using tetrabutylammonium fluoride (TBAF) in pyridine, occurred in very high yield. After conversion to the trichloroacetimidate coupling of the sialyl-containing trisaccharide derivative with Fmoc-Thr/Ser-OPfp, using silver trifluoromethanesulfonate (AgOTf) as a promoter in dichloromethane, gave the target building blocks in good yields.