Total synthesis of the d-acofriose-containing trisaccharide repeating unit of the O-antigen from Azospirillum brasilense JM6B2

Abstract

The unique D-acofriose (6-deoxy-3-O-methyl-D-mannose) unit present in the target oligosaccharide was synthesized from commercially available D-mannose in six steps with ∼50% overall yield. The synthesis was found to be equally successful at the multigram scale (100 mmol). 2-Bromoethyl α-L-fucopyranoside, required at the reducing end, was prepared exclusively via H₂SO₄–silica promoted Fischer glycosylation. The influence of the protecting group at the 3-position of the fucosyl moiety on glycosylation at the 4-position was studied and ether protection was found to be essential over ester protection. Further global deprotection gave the target conjugation-ready trisaccharide in 34% overall yield.