Oxidation of sialic acid using hydrogen peroxide as a new method to tune the reducing activity

Functionalized sialic acids are useful intermediates to prepare a wide range of biological products. As they often occur at a non-reducing terminal of oligosaccharides, the most used technique to activate them is by periodate-mediated oxidation of their glycerol side chain. Here, we describe an alternative, non toxic, and environmentally-friendly method to activate the sialic acid residues by hydrogen peroxide oxidation. Four oxidative systems involving H2O2, EDTA, iron chloride, and UV light were studied and the products obtained were analyzed by LC-MS and NMR, before and after a derivatization reaction. At first, we observed, for each system, an irreversible decarbonylation reaction at the reducing end. Then, the decarbonylated sialic acid (DSA) was oxidized and fragmented into a mix of carbonyls and carboxyl acids, more or less fast according to the experimental conditions. Analysis of the reaction indicated an apparent radical mechanism and heterolytic alpha-hydroxy-hydroperoxide cleavages. The modest reducing activity was mainly explained as a consequence of over-oxidation reactions. (C) 2014 Elsevier Ltd. All rights reserved.