Concise synthesis of di- and trisaccharides related to the O-antigens from Shigella flexneri serotypes 6 and 6a,based on late stage mono-O-acetylation and/or site-selective oxidation

Shigella flexneri serotypes 6 and 6a are closely related bacteria causing shigellosis in humans. Their O-antigens are {→4)-β-d-GalpA-(1→3)-β-d-GalpNAc-(1→2)-[3Ac/4Ac]-α-l-Rhap-(1→2)-α-l-Rhap-(1→}_n acidic polysaccharides ({AB_AcCD}_n), which only differ in the degree of O-acetylation. A concise synthesis of two disaccharides (BC, B_AcC) and four trisaccharides, representing portions and/or analogs of the O-antigens, is described. A protected intermediate compatible with late stage 3_C-O-acetylation, and/or galactosyl (A°) to galacturonic acid (A) conversion, was designed and assembled from trichloroacetimidate and thioglycoside donors tuned for high yielding glycosylation and excellent stereocontrol. The galacturonic moiety was efficiently introduced from galactose using a TEMPO/NaOCl/NaClO₂-based oxidation protocol optimized for full compatibility with sensitive moieties, such as allyl ethers and acetates. Final Pd/C-mediated deprotection provided the targets, including the propyl glycoside AB_AcC, its non O-acetylated counterpart ABC, and the non acidic analogs A°B_AcC and A°BC. The BC and ABC oligosaccharides are also portions of the O-antigen from Escherichia coli O147, which causes diarrhea in pigs.