Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

Abstract

Capsular polysaccharides of pathogenic bacteria have been reported to be effective vaccines against diseases caused by them. Providencia stuartii is a class of enterobacteria of the family Providencia that is responsible for several antibiotic resistant infections, particularly urinary tract infections of patients with prolonged catheterization in hospital settings. Towards the goal of development of vaccine candidates against this pathogen, we herein report the total synthesis of a trisaccharide repeating unit of the O-antigen polysaccharide of the P. stuartii O49 serotype containing the →6)-β-ᴅ-Galp-(1→3)-β-ᴅ-GalpNAc(1→4)-α-ᴅ-Galp(1→ linkage. The synthesis of the trisaccharide repeating unit was carried out first by a linear strategy involving the [1 + (1 + 1 = 2)] assembly, followed by a one-pot synthesis involving [1 + 1 + 1] strategy from the corresponding monosaccharides. The one-pot method provided a higher yield of the protected trisaccharide intermediate (73%) compared to the two step synthesis (66%). The protected trisaccharide was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside.