Oxidative deamination of amino sugars: recent advances

Abstract

An overview of the oxidative deamination of N-acetylneuraminic acid derivatives (Neu5Ac) leading to the formation of ketodeoxynonulosonic acid (KDN), its stereoisomers and glycosides is presented. A brief historical introduction to the deamination is given, followed by a description of recent advances in reaction conditions, which have allowed application of the process to Neu5Ac thioglycosides, and that have enabled the range of nucleophiles incorporated in the course of the reaction to be extended beyond the original acetate and azide. Recent advances resulting in derivatization of the Neu55Ac 4-position concomitant with replacement of the acetamido group, via the presumed intermediacy of a vinyl diazonium ion, are then described. The literature on the mechanism of the deamination reaction is next considered leading to the presentation of an overall mechanistic framework that accounts for all observations to date. Finally, the application of the deamination reaction to complex Neu5Ac-based oligosaccharides and other aminosugars is presented. settling on the latter as the optimal reagent for further studies. Subsequent reports focused on the N → O migration of the acyl group to form a diazo intermediate, which eliminated nitrogen under thermal conditions giving rise to the corresponding esters. The deamination reaction was studied from multiple angles to ascertain the influence of the alkyl and acyl groups, solvent, and temperature, eventually leading White to propose a mechanism accounting for the formation of various products.