Synthesis of an unusual hexasaccharide repeating unit from the cell wall polysaccharide ofEubacterium saburreumstrain T19

Eubacterium saburreumis one of the human oral pathogens and has been proved to play a significant role in the development of periodontal diseases. The cell-surface polysaccharides expressed by this microorganism are attractive targets for the development of carbohydrate-based diagnostic tools or therapeutics against oral bacteria. Here, we report the first chemical synthesis of a structurally unusual hexasaccharide repeat1found in the cell wall polysaccharide ofE. saburreumstrain T19. This linear oligosaccharide is composed of two parts: one is an alpha-(1 -> 2)-linkedd-fucofuranosyl disaccharide, and the other is an alternating beta-(1 -> 3)- and (1 -> 6)-linkedd-glycero-d-galacto-heptopyranosyl tetrasaccharide. The two fragments are connectedviaan alpha-d-fucofuranosidic linkage. A number of synthetic challenges had to be addressed, including the development of new chemistry for efficient formation ofd-galactoheptopyranoside, the development of stereoselective glycosylation methods for the construction of 1,2-cis-alpha-d-fucofuranosidic bonds, and the screening of appropriate conditions for the assembly of the sterically congested trisaccharide portion at the non-reducing end of the target molecule. Through a convergent [3 + 3] coupling strategy, the left trisaccharide thioglycoside donor17dand the right trisaccharide 3,4-diol acceptor26were efficiently forged together to generate the whole molecular backbone, thus leading to the total synthesis of1.