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Total synthesis of a structurally complex zwitterionic hexasaccharide repeating unit of polysaccharide B from Bacteroides fragilis via one-pot glycosylation

Year: 2024
Type: article
Abstract: Zwitterionic polysaccharides (ZPSs) present on the surface of a common gut commensal Bacteroides fragilis are endowed with unique immunological properties as they can directly bind to T-cells in the absence of protein conjugation. ZPSs are therefore considered to be potential antigens for the development of totally carbohydrate-based vaccines. Herein, we disclose the first total synthesis of a highly branched phosphorylated zwitterionic capsular polysaccharide repeating unit of Bacteroides fragilis. The hexasaccharide repeating unit bearing six different monosaccharides comprises three 1,2-cis-glycosidic linkages, a challenging 1,2-trans linkage in D-QuipNAc-β-(1→4)-D-Gal motif, and a 2-aminoethyl phosphonate appendage. The synthesis of target ZPS was accomplished utilizing an expeditious, highly stereoselective and convergent (1 + 2 + 2 + 1) one-pot glycosylation strategy. The striking features include efficient synthesis of rare deoxy amino sugars D- and L-quinovosamine, stereoselective installation of three 1,2-cis glycosidic linkages, glycosylation of D-quinovosamine donor with a sterically crowded, poorly reactive 4-OH galactose moiety, as well as late stage phosphorylation. Zwitterionic polysaccharides present on the surface of a common gut commensal Bacteroides fragilis are considered to be potential antigens for the development of totally carbohydrate-based vaccines. Here, the authors report the total synthesis of a highly branched phosphorylated zwitterionic capsular hexasaccharide repeating unit of Bacteroides fragilis via a one-pot glycosylation strategy.
DOI: 10.1038/s42004-024-01296-y
Language: English
Field: Chemistry
Open Access status: gold
Estimated APC paid: $3,690
Award: G648732289
OpenAlex ID: W4402581543
FWCI: 1.111
Cites: 55
Cited by: 8
Related to: 10