Pseudomonas aeruginosa belongs to the group of three "critical priority" multi-drug-resistant pathogens listed by WHO and is responsible for severe and often deadly infections such as bloodstream infections and pneumonia. Staphylococcus aureus is also a "high priority" pathogen which is a major cause of serious nosocomial infections such as bacteremia, sepsis, and endocarditis. Owing to their ability to adapt resistance to almost any antibiotics, vaccines against these pathogens are urgently required. These pathogens express structurally unique and densely functionalized glycans on their surfaces which are absent on the host cells. Such carbohydrate antigens are valuable targets for the development of glycoconjugate vaccines and diagnostics. Here, we report the first total synthesis of the conjugation-ready trisaccharide repeating unit of Pseudomonas aeruginosa O11 via a highly stereoselective and efficient assembly of a rare Lfucosamine-and D-fucosamine-containing 1,2-cis-linked disaccharide motif and its regioselective glycosylation at O3. A systematic study was conducted for the notoriously difficult glycosylation with the most unreactive axial 4-OH of the rare disaccharide, and the successful outcome was utilized to accomplish the total synthesis of an aminopropyl linker-attached trisaccharide repeating unit of Staphylococcus aureus capsular polysaccharide type 5, which is also a potential antigen for immunotherapy and vaccine development. The judicious selection of protecting groups and reaction conditions allowed the stereoselective assembly and selective functional group interconversions to access the structurally complex linker-attached trisaccharide repeating units, which are valuable tools for immunological evaluation and vaccine development. The strategy is useful for the synthesis of other structurally related complex glycans.

Bacteria often contain rare deoxy amino sugars which are absent in the host cells. This structural difference can be harnessed for the development of vaccines. Over the last fifteen years, remarkable progress has been made toward the development of novel and efficient protocols for obtaining the rare sugar building blocks and their stereoselective assembly to construct conjugation ready bacterial glycans. In this review, we discuss the total synthesis of a variety of rare sugar containing bacterial glycoconjugates which are potential vaccine candidates.

The first total synthesis of the trisaccharide repeating unit of the O-specific polysaccharide of Pseudomonas fluorescens BIM B-582 is reported. This efficient synthesis involves consecutive 1,2- cis glycosylations including β-l-rhamnosylation and α selective coupling of rare 4-deoxy-d- xylo-hexose as the key steps. The synthetic trisaccharide is equipped with an aminopropyl linker at the reducing end to allow for conjugation to proteins and microarrays for further immunological studies.

The MECA-79 antigen is a sulfated mucin type core-1 extended O-glycan which is a potential antiinflammatory agent. Herein we report a total synthesis of MECA-79 via a convergent [2 + 2] glycosylation route. The synthesis relies on efficient transformation of D-glucosamine into the orthogonally protected Tn antigen derivative and its elaboration into the TF antigen en route to MECA-79. Scheme 4 Global deprotection and completion of the synthesis of MECA-79. 58574 | RSC Adv., 2014, 4, 58573-58580 This journal is