Uronic Acids in Oligosaccharide and Glycoconjugate Synthesis

Abstract

This chapter describes the assembly of uronic acid containing oligosaccharides and glycoconjugates. Two strategies are available to access these target molecules, namely a pre-glycosylation oxidation approach, in which uronic acid building blocks are used, and a post-glycosylation oxidation strategy, which employs an oxidation step after the assembly of the oligosaccharide chain. Because uronic acid building blocks are generally considered to be less reactive than their non-oxidized counterparts, the latter approach has found most application in carbohydrate synthesis. With the aid of selected examples of recent syntheses of biologically relevant oligosaccharides and glycoconjugates, the reactivity of different uronic acid building blocks is evaluated. From these examples it is apparent that the generally assumed low reactivity of uronic acids does not a priori rule out an efficient assembly of these target compounds. Besides influencing the reactivity of a given pyranoside, the C-5 carboxylic acid function can also have a profound effect on the stereochemical course of a glycosylation reaction, which can be exploited in the stereoselective formation of glycosidic bonds.

Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug‐Resistant Enterobacteriaceae

“…A strategy in which the primary alcohol of 10 was oxidized and protected as a benzyl ester and then used as an acceptor in a glycosylation with 1 resulted in a trace amount of trisaccharide 14 (Scheme S3). The carboxylic acid of the acceptor probably reduced the reactivity of the neighboring C‐4 alcohol, thereby complicating the glycosylation 17a…”

Production and applications of carbohydrate-derived sugar acids as generic biobased chemicals

“…Therefore synthesis of uronic acid containing polymers has gained interest with a focus on medical applications (Codée et al, 2011;van den Bos et al, 2007). One of the most extensively studied uronic acid containing polymers is the glycosaminoglucan heparin, containing D-glucuronic acid and L-iduronic acid moieties, and its sulfates (Petitou & van Boeckel, 2004;van den Bos et al, 2007).…”

“…The pyranose forms of hexose derivatives are the most common forms of uronic acids (Collins & Ferrier, 1995). Synthesis of uronic acids and their derivatives has been extensively reviewed and has not been considered in detail here (Codée et al, 2011;Timoshchuk, 1995;van den Bos, 2007). Chemical synthesis of uronic acids and their derivatives is often tedious.…”

Effective Synthesis of α‐d‐GlcN‐(1→4)‐d‐GlcA/l‐IdoA Glycosidic Linkage under Gold(I) Catalysis

“…Due to their low reactivity, side reactions such as epimerization and β‐elimination can occur under the acidic conditions required to activate the corresponding SR, TCA, and PTFAI donors. Indeed, construction of the α‐ d ‐GlcN‐(1→4)‐ d ‐GlcA/ l ‐IdoA linkage with uronate acceptors usually leads to moderate yields and α selectivity . Alternatively, the more reactive glucose/idose counterparts are used as acceptors, which are subjected to oxidation at a late stage of the synthesis .…”