Dithiasuccinoyl (Dts) amino-protecting group used in syntheses of 1,2-trans-amino sugar glycosides

Abstract

Suitable protected D-glucosamine derivatives possessing the N-dithiasuccinoyl (N-Dts) protecting group of the amino function have been applied in a new alternative route to 1,2-trans-glycosylation. The O-(3,4,6-tri-O-acetyl-2-deoxy-2-dithiasuccinoylamino-β-D-glucopyranosyl) tri-chloroacetimidate 7 has been used to prepare corresponding β-glycosides in good yields promoted by Lewis acids. The N-dithiasuccinoyl protecting group was easy to remove by thiolysis using 2-sulfanylethanol or dithiothreitol or reductively using sodium boranuide, thus affording, after N-acetylation, the corresponding N-acetyl-β-D-glucosamine glycosides. It has been demonstrated that it is possible to reduce the Dts group in the presence of an azido group selectively by sodium boranuide or the Dts- and the azido group simultaneously by dithiothreitol, using diisopropylethylamine as a catalyst. The syntheses of the building blocks. N^α-Fmoc-Ser(Ac₃-β-D-GlcNDts)-OPfp 10 and N^α-Fmoc-Thr(Ac₃-β-D-GlcNDts)-OPfp11, suitable for the solid-phase glycopeptide synthesis of β-O linked GlcNAc bearing glycopeptides are described. Furthermore, the preparation of the N^α-Fmoc-Asn[Ac₃-β-D-GlcNAc-(1 → 4)-Ac₂-β-D-GlcNAc]-OPfp building block 19, suitable for the solid-phase synthesis of N-glycopeptides, and the synthesis of the β-D-GlcNAc(1 → 6)-D-GalNAc disaccharide 27, a mucin core structure, demonstrate the use of N-dithiasuccinoyl protection in oligosaccharide synthesis.