Synthesis of Glycosides of Glucuronic, Galacturonic and Mannuronic Acids: An Overview

Abstract

Uronic acids are carbohydrates present in relevant biologically active compounds. Most of the latter are glycosides or oligosaccharides linked by their anomeric carbon, so their synthesis requires glycoside-bond formation. The activation of this anomeric center remains difficult due to the presence of the electron-withdrawing C-5 carboxylic group. Herein we present an overview of glucuronidation, mannuronidation and galacturonidation reactions, including syntheses of prodrugs, oligosaccharides and stereochemical aspects.

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

“…A direct approach using 2-azido-2-deoxymannuronyl donor 2 and acceptor 4 gave a low yield of disaccharide probably due to low reactivity of uronyl donors (Scheme S2). [17] …”

“…Probably, the carboxylic acid of the acceptor reduced the reactivity of the neighboring C-4 alcohol thereby complicating the glycosylation. [17a] …”

Divergent synthetic approach to 6′′-modified α-GalCer analogues

“…12,33,34 This may be due to the deactivating effect of the electron-withdrawing C-5 carboxylic group, making the galacturonidation particularly challenging. 35 In addition, in their efforts to assess the influence of a pyranosyl C-5 carboxylate ester on the stereochemical outcome of glycosylation reactions, van der Marel and coworkers demonstrated that a C-5 ester is 1,5- cis or β-directing as opposed to C-5 methylene oxybenzyl, which induces little selectivity. 36 This is reflected in the synthesis of the Sphingomonas glycolipid 6 by Seeberger et al , who found that even after extensive optimization (including galactose protecting groups), glycosylation was achieved with a maximum 4.2:1 ratio of the α- and β-anomers.…”

Efficient synthesis of baicalin and its analogs

“…This task is challenging in carbohydrate chemistry due to the low reactivity of the corresponding glycuronic donors. 12 In the case of baicalin, it is even more challenging because the glucuronic residue is attached to a phenolic hydroxyl group rather than an alkyl hydroxyl group. Phenolic -OHs are known as lowyielding glycosylation acceptors due to their reduced nucleophility than that of their alcohol counterparts.…”