Chemical synthesis of modified D-mannuronate building blocks: prospects for modified alginates

Abstract

Alginate is an anionic polysaccharide comprised of β˗1,4˗linked D˗mannuronic acid (M) and L˗guluronic acid (G). The polymer is naturally harvested from seaweed and is widely exploited in various biotechnological and biomedical applications, due to the multitude of physicochemical characteristics it possesses, predominantly owed to the presence of charged C5˗carboxylic acid groups. Modification of the carboxylates would enable the development of alginate systems possessing novel physicochemical properties.
Herein is presented for the first time the synthesis of C6˗hydroxamate and C6˗tetrazole D˗ManA building blocks. The optimised experimental protocols developed, delivered the building blocks in high yields and multi˗gram amounts. C6˗hydroxamate building blocks were evaluated for the chemical glycosylation of modified alginate oligosaccharides by employing an iterative approach, whereby the non˗reducing end was extended. Initial design of the strategy allowed access to the α˗ and β˗linked mixed˗system alginate disaccharides. The results derived from their evaluation emphasises the important contribution of both C6˗hydroxamate donor and acceptor reactivity. An additional objective presented was the chemical synthesis of C6˗bioisosteric D˗ManA 1˗phosphate building blocks.