Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

Abstract

SummaryThe present work describes efficient avenues for the synthesis of the trisaccharide repeating unit [α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap] associated with the A-band polysaccharide of Pseudomonas aeruginosa. One of the key steps involved 6-O-deoxygenation of either partially or fully acylated 4,6-O-benzylidene-1-thiomannopyranoside by radical-mediated redox rearrangement in high yields and regioselectivity. The D-rhamno-thioglycosides so obtained allowed efficient access to the trisaccharide target via stepwise glycosylation as well as a one-pot glycosylation protocol. In a different approach, a 4,6-O-benzylidene D-manno-trisaccharide derivative was synthesized, which upon global 6-O-deoxygenation followed by deprotection generated the target D-rhamno-trisaccharide. The application of the reported regioselective radical-mediated deoxygenation on 4,6-O-benzylidene D-manno thioglycoside (hitherto unexplored) has potential for ramification in the field of synthesis of oligosaccharides based on 6-deoxy hexoses.

Total Syntheses of Conjugation-Ready Trisaccharide Repeating Units of Pseudomonas aeruginosa O11 and Staphylococcus aureus Type 5 Capsular Polysaccharide for Vaccine Development

“…Pseudomonas aeruginosa also plays a vital role in the pathogenesis of cystic fibrosis and mainly causes chronic lung infection in CF patients. , Pseudomonas aeruginosa can cause serious ulcerative keratitis in individuals who wear contact lenses . Currently there are no licensed vaccines available against Pseudomonas aeruginosa , although there are many studies in this direction which have evaluated a range of antigens including outer-membrane proteins, O -polysaccharides, exopolysaccharides, toxins, pili, and flagella. , The chemical synthesis of a few glycans such as β- d -mannose containing oligosaccharide fragments related to its exopolysaccharide, pseudaminic acid containing the trisaccharide of Pseudomonas aeruginosa 1244 pilin glycan, and the d -rhamnose-containing trisaccharide related to the A band polysaccharide have been reported so far. The rare-sugar-containing trisaccharide repeating unit of P. aeruginosa O11 lipopolysaccharide with a proposed structure of →2)-β- d -Glc-(1 → 3)-α- l -FucNAc-(1 → 3)-β- d -FucNAc-(1→ (Figure ) is a potential vaccine candidate. , The chemical synthesis of conjugation-ready trisaccharide repeating unit 1 has not been reported yet and is highly warranted.…”

“…13 Currently there are no licensed vaccines available against Pseudomonas aeruginosa, although there are many studies in this direction which have evaluated a range of antigens including outer-membrane proteins, O-polysaccharides, exopolysaccharides, toxins, pili, and flagella. 14,15 The chemical synthesis of a few glycans such as β-D-mannose containing oligosaccharide fragments related to its exopolysaccharide, 16 pseudaminic acid containing the trisaccharide of Pseudomonas aeruginosa 1244 pilin glycan, 17 and the D-rhamnose-containing trisaccharide related to the A band polysaccharide 18 have been reported so far. The raresugar-containing trisaccharide repeating unit of P. aeruginosa O11 lipopolysaccharide with a proposed structure of →2)-β-D- 1) is a potential vaccine candidate.…”

Simple Carbohydrate-Derived Multifunctional Gels

“…Compounds 1 and 2 were prepared from the known compounds 3 and 4 respectively. By a single step reaction using benzaldehyde dimethyl acetal in the presence of H 2 SO 4 ‐silica in dry CH 3 CN, the desired derivatives 1 and 2 were obtained in 89% and 92% yields respectively (Scheme ).…”

Deoxy sugars. General methods for carbohydrate deoxygenation and glycosidation

“…The β-scission in 67 is influenced by the angular torsion of the fused bicyclic structure. 163 As an example, Ghosh and co-workers based the synthesis of various bacterial rare sugars from d -glucose and d -mannose derivatives, 164 and the synthesis of the α- d -rhamnose trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa 165 in this reaction.…”