EFFICIENT SYNTHESES OF CORE-1, CORE-2, CORE-3 AND CORE-4 BUILDING-BLOCKS FOR SPS OF MUCIN O-GLYCOPEPTIDES BASED ON THE N-DTS-METHOD

The structures beta-D-Gal-(1-->3)-alpha-D-GalNAc-(1-->O)-L-Thr, ta-D-G lcNAc-(1-->6)]-alpha-D-GalNAc-(1-->O)-L-Thr, beta-D-GlcNAc-(1-->3)-alp ha-D-GalNAc-(1-->O)-L-Thr and eta-D-GlcNAc-(1-->6)]-alpha-D-GalNAc-(1- ->O)-L-Thr represent the core 1, core 2, core 3 and core 4 structures, respectively, of mucin-type O-glycoproteins, Efficient syntheses of t he corresponding building blocks 8, 12, 14 and 17 are described. Stere oselective glycosylation of different N-alpha-Fmoc-Thr(alpha-D-GalN(3) )-OPfp derivatives with the 2-dithiasuccinimido glycosyl donor 10, fol lowed by simultaneous in situ reduction of the N-dithiasuccinoyl (N-Dt s) and azido functionalities with zinc dust in tetrahydrofuran/ acetic acid in the presence of acetic anhydride afforded the protected build ing blocks 8, 12, 14 and 17. These building blocks can be used directl y in solid-phase synthesis (SPS) of core 1, core 2, core 3 and core 4 mucin O-glycopeptides, Further modification of the carbohydrate moiety on the solid phase is not required.