Total Synthesis of the Complete Protective Antigen of Vibrio cholerae O139

The first chemical synthesis of the complete protective O-antigen of a human-disease-causing pathogenic bacterium is described. The synthesis involved a protecting-group strategy that facilitated the regioselectivity of the key transformations, stereoselective glycosylation reactions, and enabled the one-step global deprotection of the completely assembled, fully protected, phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final amino-group-functionalized, linker-equipped antigen was obtained in a form ready for conjugation to suitable carriers, for example, proteins, to yield immunogens.