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

Abstract

Shigella sonnei surface polysaccharides are well-established protective antigens against this major causeo fd iarrhoeal disease.T hey also qualify as unique zwitterionic polysaccharides (ZPSs)f eaturing ad isaccharide repeating unit made of two 1,2-trans linked rare aminodeoxy sugars, a 2-acetamido-2-deoxy-l-altruronic acid (l-AltpNAcA)a nd a2acetamido-4-amino-2,4,6-trideoxy-d-galactopyranose (AAT). Herein,t he stereoselective synthesis of S. sonnei oligosaccharides comprising two, three and four repeating units is reported for the first time. Severals ets of up to seven pro-tectingg roups wereexplored,s hedding light on the singular conformational behavior of protected altrosamine and altruronic residues. Ad isaccharide buildingb lock equipped with three distinct N-protectingg roups and featuring the uronate moiety already in place was designed to accomplish the iterative high yieldingg lycosylation at the axial 4-OH of the altruronate componenta nd achieve the challenging full deprotection step. Key to the successfulr oute was the use of a diacetyls trategy whereby the N-acetamido group of the l-AltpNAcAism asked in the form of an imide.

Total Syntheses of Conjugation‐Ready Repeating Units of Acinetobacter baumannii AB5075 for Glycoconjugate Vaccine Development

“…Possibly, introduction of the TCA group may be responsible for the decrease in the nucleophilicity of receptor 34. [36] In order to improve the efficiency of the glycosylation to obtain disaccharide 45, the Fmoc protecting group in 25 was replaced with a strong electron-donating tert-butyldimethylsilyl ether (TBS) group. Glucuronate building block 46 was obtained after protection of the C4-OH as a TBS ether in 24 in 90 % yield (Scheme 5A).…”

Toward a Multivalent Synthetic Oligosaccharide-Based Conjugate Vaccine against Shigella: State-of-the-Art for a Monovalent Prototype and Challenges

“…Of special interest, the S. sonnei O-Ag represents a unique challenge owing to its zwitterionic disaccharide repeat [ 20 ]. Nevertheless, oligosaccharides representing O-Ag segments of various composition and length were synthesized [ 21 , 22 ], paving the way to a library of neoglycoconjugates demonstrating remarkable immunogenicity in mice [ 23 ]. Alternatively, the synthesis of a large set of S. flexneri 6 (SF6) oligosaccharides enabled the identification of an immunodominant epitope central to further developments (Chassagne et al, unpublished data) [ 24 ].…”

Synthesis of L‐Hexoses: An Update

“…Kulkarni and co‐workers pioneered the regioselective displacement of 2,4‐bistriflates of hexopyranoses to access a variety of rare, bacterial D‐ and L‐deoxy amino sugars in an expedient way [70] . These developments have greatly helped synthesis of a variety of bacterial glycoconjugates [71–74] . The other popular method to access rare deoxy amino L‐hexoses is azido nitration/selenation of L‐fucal or L‐rhamnal [75,76] .…”

“…[70] These developments have greatly helped synthesis of a variety of bacterial glycoconjugates. [71][72][73][74] The other popular method to access rare deoxy amino L-hexoses is azido nitration/selenation of L-fucal or L-rhamnal. [75,76] The progress in the synthesis of rare sugars containing bacterial glycoconjugates has been recently reviewed.…”