Synthesis of an Aminooxy Derivative of the Tetrasaccharide Repeating Unit of Streptococcus dysgalactiae 2023 Polysaccharide for a PS A1 Conjugate Vaccine

Abstract

A highly efficient and stereocontrolled synthesis of an aminooxy derivative of the tetrasaccharide repeating unit of a rhamnose-rich polysaccharide isolated from the cell envelop of bovine mastitis Streptococcus dysgalactiae 2023 is reported for the first time. The synthesis was accomplished utilizing a stereoselective and convergent [2 + 2] glycosylation strategy inclusive of a disaccharide Schmidt donor and an inclusive rhamnose disaccharide acceptor. The synthetic aminooxy tetrasaccharide was conjugated to T-cell stimulating immunogen PS A1 from Bacteroides fragilis ATCC 25285/NCTC 9343 via a physiologically stable oxime linkage to furnish the first semisynthetic bacterial-based immunogen construct targeting S. dysgalactiae 2023. The synthetic tetrasaccharide was assembled in 19 steps with a ∼5.0% overall yield.

An update on environmental mastitis: Challenging perceptions

“…Encouraging preliminary reports on reduction of S. dysgalactiae infection in a dry-cow challenge model through use of the surface receptor protein GapC have not led to a vaccine, even KLAAS AND ZADOKS | 177 though there were hopes that such a vaccine could provide crossprotection to S. dysgalactiae, S. agalactiae and S. uberis (Bolton et al, 2004;Perez-Casal, Prysliak, & Potter, 2004). More recently, the polysaccharide envelope of S. dysgalactiae has been investigated as a potential vaccine target, starting with stereocontrolled synthesis of a tetrasaccharide repeating unit coupled to a T-cell-stimulating immunogen (Ghosh, Nishat, & Andreana, 2016). It will be interesting to see whether involvement of additional disciplines, such as chemistry, can bring the dream of gram-positive mastitis vaccines closer.…”

A Diazido Mannose Analogue as a Chemoenzymatic Synthon for Synthesizing Di‐N‐acetyllegionaminic Acid‐Containing Glycosides

“…Compound 7 was then treated with trifluoromethanesulfonic anhydride (Tf 2 O) and pyridine to form the corresponding 2,4-bistriflate [16] which upon treating with 2.5 equivalent of tetrabutylammonium azide (TBAN 3 ) in anhydrous toluene at 70 °C to reflux, [17] 6-deoxy-D-mannose derivative 8 was formed in 2 hours in 93% yield. Debenzoylation and ceric ammonium nitrate-catalyzed removal of the p -methoxyphenyl group [18] produced 2,4-diazido-2,4,6-trideoxy mannose (6deoxyMan2,4diN 3 , 9 ) in 81% yield. Overall, the production of 6deoxyMan2,4diN 3 ( 9 ) from D-fucose ( 5 ) was achieved in eight steps with an overall yield of 60%.…”

“…Different strategies were tested for conversion of the azido groups in the glycosides synthesized (products [13][14][15][16][17][18] into N-acetyl groups to form the desired Leg5,7Ac 2 -containing glycosides 19-24.Aconventional Perlman catalyst mediated azide-to-amine reduction [27] followed by selective…”

Carbohydrate‐based vaccines for oncotherapy

“…In addition, similar results were obtained from adjuvant‐free vaccinated mice, which also implied that PS A1 acts as not only a carrier, but also an adjuvant . They were further inspired to synthesize numerous ZPSs‐based vaccine candidates employing their linker‐free antigen synthesis strategy . With immune response directed toward a linker itself, immune suppression to the target antigen could occur …”

“…[167][168][169][170] They were further inspired to synthesize numerous ZPSs-based vaccine candidates employing their linker-free antigen synthesis strategy. [171][172][173] With immune response directed toward a linker itself, immune suppression to the target antigen could occur. 62 Besides, they conjugated TF to PS A1 obtaining TF-PS A1 vaccine construct, and in preclinical trial mice could elicit TF-specific polyclonal antibodies, which were able to recognize TF-expressing cancer cells efficiently.…”