Synthesis of an unusual hexasaccharide repeating unit from the cell wall polysaccharide of Eubacterium saburreum strain T19

Abstract

Eubacterium saburreum is 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 repeat 1 found in the cell wall polysaccharide of E. saburreum strain T19. This linear oligosaccharide is composed of two parts: one is an α-(1 → 2)-linked D-fucofuranosyl disaccharide, and the other is an alternating β-(1 → 3)- and (1 → 6)-linked D-glycero-D-galacto-heptopyranosyl tetrasaccharide. The two fragments are connected via an α-D-fucofuranosidic linkage. A number of synthetic challenges had to be addressed, including the development of new chemistry for efficient formation of D-galactoheptopyranoside, the development of stereoselective glycosylation methods for the construction of 1,2-cis-α-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 donor 17d and the right trisaccharide 3,4-diol acceptor 26 were efficiently forged together to generate the whole molecular backbone, thus leading to the total synthesis of 1.