A building block approach to the synthesis of a family of S-linked α-1, 6-oligomannosides. (24th June 2016) - Belz, Tyson
Highlights: A family of S-linked α-1, 6-oligomannosides up to hexasaccharides were synthesized. Compounds were assembled from preformed sulfur-containing mannose building blocks. The thioglycoside linkages formed by coupling of anomeric thiolates with 6-iodo sugars. Reducing-end and non-reducing end extensions were investigated. Graphical abstract: Abstract: The syntheses of α-1, 6-S-linked methyl di-, tetra- and hexamannosides are reported. The sulfur linkages are generated through coupling of thiolates (derived from anomeric thioacetates or isothiouronium bromides) with 6-deoxy-6-iodo sugars. Two approaches are detailed that involve [2 + 2 + 2] construction from either the reducing end or the non-reducing end. In constructing from the reducing end, coupling of a disaccharide thioacetate with a 6'-iodo reducing end disaccharide, followed by activation of the resulting tetrasaccharide to a 6'''-iodide, and iterative coupling with the same disaccharide thioacetate afforded the S-linked hexasaccharide, as well as the intermediate di- and tetrasaccharides. On the other hand, construction from the non-reducing end involved coupling of the above disaccharide thioacetate with an anomeric S -trityl protected 6'-iodo disaccharide. The resulting S -trityl tetrasaccharide was converted to a tetrasaccharide thioacetate, which was coupled with the same anomeric S-trityl protected 6'-iodo disaccharide to afford the hexasaccharide, which was elaborated to the methyl thioglycoside. The developed methodology may prove useful for the construction of other S-linked oligosaccharides.