Efficient syntheses of core 1, core 2, and core 3 and core 4 building blocks for SPS of mucin O-glycopeptides based on the N-Dts-method

Abstract

The structures β-D-Gal-(1→3)-α-D-GalNAc-(1-→O)-L-Thr, β-D-Gal-(1→3)-[β-D-GIcNAc-(1→6)]-α-D-GalNAc-(1→O)-L-Thr, β-D-GlcNAc-(1→3)-α-D;GalNAc-(1→O)-L-Thr and β-D-GlcNAc-(1→3)-[β-D-GlcNAc(1→6)]-α-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 the corresponding building blocks 8, 12, 14 and 17 are described. Stereoselective glycosylation of different N^α-Fmoc-Thr(α-D-GalN₃)-OPfp derivatives with the 2-dithiasuccinimido glycosyl donor 10, followed by simultaneous in situ reduction of the N-dithiasuccinoyl (N-Dts) and azido functionalities with zinc dust in tetrahydrofuran/acetic acid in the presence of acetic anhydride afforded the protected building blocks 8, 12, 14 and 17. These building blocks can be used directly 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.