The gut pathogen Clostridium bolteae has been associated with the onset of autism spectrum disorder (ASD). To create vaccines against C. bolteae,itisimportant to identify exact protective epitopes of the immunologically active capsular polysaccharide (CPS). Here,aseries of C. bolteae CPS glycans,u pt oa no ctadecasaccharide,w as prepared. Keyt o achieving the total syntheses is a[2+ +2] coupling strategy based on a b-d-Rhap-(1!3)-ad -Manp repeating unit that in turn was accessed by astereoselective b-d-rhamnosylation. The 4,6-O-benzylidene-induced conformational locking is ap owerful strategy for forming a b-d-mannose-type glycoside.Anindirect strategy based on C2 epimerization of b-d-quinovoside was efficiently achieved by Swern oxidation and borohydride reduction. Sequential glycosylation, and regioselective and global deprotection produced the disaccharide and tetrasaccharide,u pt ot he octadecasaccharide.G lycan microarray analysis of sera from rabbits immunized with inactivated C. bolteae bacteria revealed ahumoral immune response to the diand tetrasaccharide,b ut none of the longer sequences.T he tetrasaccharide may be ak ey motif for designing glycoconjugate vaccines against C. bolteae.

The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipo‐polysaccharide (LPS) O‐antigens that contain Lewis determinant oligosaccharides and unique dd‐heptoglycans has not yet been identified. Reported here is the first total synthesis of H. pylori serotype O6 tridecasaccharide O‐antigen containing a terminal Ley tetrasaccharide, a unique α‐(1→3)‐, α‐(1→6)‐, and α‐(1→2)‐linked heptoglycan, and a β‐d‐galactose connector, by an [(2×1)+(3+8)] assembly sequence. Seven oligosaccharides covering different portions of the entire O‐antigen were prepared for immunological investigations with a particular focus on elucidation of the roles of the dd‐heptoglycan and Ley tetrasaccharide. Glycan microarray analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the α‐(1→3)‐linked heptoglycan, a key motif for designing glycoconjugate vaccines for H. pylori serotype O6.

Staphylococcus aureus causes a wide range of life-threatening diseases. One of the powerful approaches for prevention and treatment is to develop an efficient vaccine as antibiotic resistance greatly increases. S. aureus type 8 capsular polysaccharide (CP8) has shown great potential in vaccine development. An understanding of the immunogenicity of CP8 trisaccharide repeating unit is valuable for epitope-focused vaccine design and cost-efficient vaccine production. We report the chemical synthesis of conjugation-ready CP8 trisaccharide 1 bearing an amine linker, which effectively served for immunological evaluation. The trisaccharide 1-CRM197 conjugate elicited a robust immunoglobulin G (IgG) immune response in mice. Both serum antibodies and prepared monoclonal antibodies recognized S. aureus strain, demonstrating that synthetic trisaccharide 1 can be an efficient antigen for vaccine development.