Rapid assembly of phosphate-bridged tetra-mannose by ionic liquid-supported oligosaccharide synthesis

An efficient ionic liquid-supported oligosaccharide synthesis (ILSOS) strategy was described for the synthesis of linear oligo-phosphomannan. A new cleavable benzyl carbamate-type IL supporter containing 5-aminopentanyl linker was designed as an acceptor IL tag to facilitate this synthesis. The chain elongation on IL tag was achieved by H-phosphonate chemistry, including condensation with α-mannosyl H-phosphonate, in situ oxidation reaction and subsequent deprotection. After four cycles, linear α-(1 → 6)-tetra-mannan phosphate was obtained with a total yield of 52.7% within 45 h. The IL tagged product exhibited a tunable solubility in polar and non-polar solvent systems that facilitate a chromatography-free purification in the assembly process. The IL tag could be easily removed after hydrogenolysis treatment after the final step, to afford an amine terminated linker at the reducing end of phosphoglycan for further conjugation with a carrier protein. This methodology offered an efficient and chromatography-free approach for the synthesis of phosphoglycan.