Many medically relevant mannoconjugates were isolated as part of N-glycans, GPI anchors, fungal cell wall, and ligands of plant or bacterial lectins. Among these, oligomannosides, linear and branched, have been shown to exhibit a wide range of biological functions. Synthesis of such polysaccharides yield valuable tools for studies of biological recognition mechanisms. Polymannosides can be assembled via linking various mannose residues by stereoselective glycosylation. In this context, regioselective masking and unmasking of hydroxy groups is often required. Among numerous mannose-containing oligosaccharides, 3,6-branched mannosides (i.e., Hex(1→3)[Hex(1→6)]Man) have been shown to exhibit important biological functions. Thus, preparation of a mannoside building block with orthogonal protecting groups at the O-3 and O-6 positions is of great interest.
We present here an efficient synthesis of the synthetic building block methyl 3-O-benzoyl-6-O-tert-butyldiphenylsilyl-2,4-di-O-tert-butyloxycarbonyl-α-D-mannopyranoside (4) from the commercially available methyl α-D-mannopyranoside 1. The described regioselective protection of the latter was achieved via a dimethyltin dichloride-catalyzed benzoylation, affording the 3-O-benzoyl mannoside 2 as the exclusive product. Compound 2 was subjected to a selective tert-butyldiphenylsilyl protection of the primary hydroxy group providing the orthogonal 3,6-bis protected mannoside 3 in good yield. The fully protected mannoside building block 4 was obtained upon treatment of 3 with Boc anhydride, 4-dimethylaminopyridine (DMAP), and pyridine. Mannopyranoside 4 is a useful precursor for chemoselective O-3 or O-6 deprotection. As such, compound 4 is a useful building block for oligosaccharide synthesis.