Science Advances

Total synthesis of zwitterionic PS A2 oligosaccharides from Bacteroides fragilis

2025-12-12

Zwitterionic polysaccharides have unique structures and can elicit T cell–dependent immune responses. To unravel their molecular mode of action and develop potential alternatives for carrier proteins in carbohydrate-based vaccines, we here describe a total synthesis of zwitterionic PS A2 oligosaccharides from Bacteroides fragilis . The pentasaccharide and decasaccharide bearing one or two repeating units were efficiently synthesized via convergent glycosylation strategy. The ingenious protecting groups have enabled the stereoselectivity of glycosylation. A unique synthetic approach was developed to introduce the chiral 3-hydroxybutanoic acid side chain on mannoheptose, which proved very challenging to form in this skeleton.

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DOI https://doi.org/10.1126/sciadv.aeb4065