Exploratory N-Protecting Group Manipulation for the Total Synthesis of Zwitterionic Shigella sonnei Oligosaccharides

Shigella sonnei surface polysaccharides are well-established protective antigens against this major cause of diarrhoeal disease. They also qualify as unique zwitterionic polysaccharides (ZPSs) featuring a disaccharide repeating unit made of two 1,2-trans linked rare aminodeoxy sugars, a 2-acetamido-2-deoxy-l-altruronic acid (l-AltpNAcA) and a 2-acetamido-4-amino-2,4,6-trideoxy-d-galactopyranose (AAT). Herein, the stereoselective synthesis of S. sonnei oligosaccharides comprising two, three and four repeating units is reported for the first time. Several sets of up to seven protecting groups were explored, shedding light on the singular conformational behavior of protected altrosamine and altruronic residues. A disaccharide building block equipped with three distinct N-protecting groups and featuring the uronate moiety already in place was designed to accomplish the iterative high yielding glycosylation at the axial 4-OH of the altruronate component and achieve the challenging full deprotection step. Key to the successful route was the use of a diacetyl strategy whereby the N-acetamido group of the l-AltpNAcA is masked in the form of an imide.