Chemical Synthesis and Antigenic Evaluation of Oligosaccharides of Bordetella hinzii O-Antigen Containing Unique Amidated 2,3-Diacetamido-2,3-dideoxy-alduronic Acids

Abstract

Bordetella hinzii is a zoonotic pathogen, which can cause brain abscess, pneumonia, bacteremia, and urinary tract infection. Vaccines are economical and effective means for combating infectious diseases. Herein, we present the first total synthesis of the highly functionalized mono- and oligosaccharides of B. hinzii O-antigen for vaccine development. The rare 2,3-diacetamidopyranoses were generated from 3-O-acetyl-2-nitroglycals via an organocatalyzed one-pot relay glycosylation method. The postglycosylation oxidation strategy was used to overcome the poor reactivity of 2,3-diacetamido-aldouronic acid building blocks in glycosylation reactions. Direct amidation of alduronic acid with NH₃ in the late stage reduced the protecting group operation and increased the synthetic efficiency. Di-tert-butylsilylidene-directed α-galactosylation method was used to construct challenging 1,2-cis-glycosidic bond. Six oligosaccharides of B. hinzii O-antigen were obtained and further conjugated to human serum albumin for antigenicity evaluation (the sera antibodies were obtained from vaccinated mouse via inactivated B. hinzii). The terminal tetrasaccharide of B. hinzii O-antigen has been identified as a potential glycol-epitope and might be useful for vaccine development against B. hinzii.