Total Synthesis of the Zwitterionic Trisaccharide Repeating Unit of Staphylococcus aureus CP8.

Zwitterionic polysaccharides are unique carbohydrates capable of eliciting T-cell-dependent responses without protein conjugation. Herein, we report the first total synthesis of the zwitterionic trisaccharide repeating unit of Staphylococcus aureus CP8 in 2.8% yield. The target features three challenging 1,2-cis glycosidic linkages and orthogonal nitrogen functionalities, one amine and two acetamido groups. These challenges were addressed using oxazolidinone-protected l-fucosamine, which enabled α-selective glycosylation while providing orthogonality with the azido group, facilitating trisaccharide assembly through direct β-mannosylation.