Super-Armed Thiomannopyranosides in the Synthesis of a Mannose-Capped Trisaccharide of Mycobacterium tuberculosis Lipoarabinomannan

Silylation of phenyl 1-thio-α-d-mannopyranoside, ethyl 1-thio-α- and β-d-mannopyranosides under different conditions was studied. Low-temperature NMR analysis revealed that the silylated products typically exist as an equilibrium of two chair conformations with a predominance of the axially rich 1C4 conformation. The dependence of the ratio of conformers on the anomeric configuration, the type of silyl groups and the nature of the aglycone was established. The fully silylated phenyl 1-thio-α-d-mannopyranoside, ethyl 1-thio-α- and β-d-mannopyranosides were tested as glycosyl donors in the synthesis of di- and trisaccharides, including one-pot synthesis. In all cases, only a-linked oligosaccharides as mixtures of conformers were formed. The obtained deprotected Manp-(1→2)-α-d-Manp-(1→5)-α-d-Araf trisaccharide 2-azidoethyl glycoside, related to the non-reducing terminal fragment of the mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis, can be used for further preparation of conjugates with proteins to provide antigens, which are important for development of new tuberculosis screening assays.