Royal Society of Chemistry Carbohydrate Chemistry: Chemical and Biological Approaches Volume 43 (Specialist Periodical Reports: Carbohydrate Chemistry)

Excerpt. © Reprinted by permission. All rights reserved. Carbohydrate Chemistry Volume 43 Chemical and Biological Approaches By Amelia Pilar Rauter, Thisbe K. Lindhorst, Yves Queneau The Royal Society of ChemistryCopyright © 2018 The Royal Society of Chemistry All rights reserved. ISBN: 978-1-78801-003-0 Contents Preface, vii, Synthesis and biological properties of imino-disaccharides and -oligosaccharides Alberto Marra and Renaud Zelli, 1, Bacterial polysaccharides as major surface antigens: interest in O-acetyl substitutions Laurence A. Mulard, 71, Regioselective glycosylation: What's new? Laurent Legentil and Vincent Ferrières, 104, Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy Paula Alexandra Videira, Filipa Marcelo and Ravneet Kaur Grewal, 135, Targeting protein-carbohydrate interactions in plant cell-wall biodegradation: the power of carbohydrate microarrays Diana O. Ribeiro, Benedita A. Pinheiro, Ana Luísa Carvalho and Angelina S. Palma, 159, Low melting carbohydrate mixtures and aqueous carbohydrates – an effective green medium for organic synthesis Palanisamy Ravichandiran and Yanlong Gu, 177, Surfactants based on green/blue sugars: towards new functionalities in formulations Louise Renault, Freddy Pessel and Thierry Benvegnu, 196, Low molecular weight carbohydrate-based hydrogelators Cédric Peyrot, Pierre Lafite, Loïc Lemiègre and Richard Daniellou, 245, CHAPTER 1 Synthesis and biological properties of imino-disaccharides and -oligosaccharides Alberto Marra and Renaud Zelli 1 Introduction Iminosugars, in the past erroneously called azasugars, are polyhydroxylated monocyclic (pyrrolidine, piperidine, azepane) and bicyclic (pyrrolizidine, indolizidine, nortropane) nitrogenated compounds that can be considered carbohydrate analogues bearing a basic nitrogen instead of the endocyclic oxygen atom (Fig. 1). These naturally occurring products are strong inhibitors of both glycosidases, the enzymes that catalyse the cleavage of glycosidic bonds in oligosaccharides and glycoconjugates, and glycosyltransferases, the enzymes that catalyse the formation of the glycosidic bond starting from an activated sugar donor. Besides the sterical and stereochemical resemblance to sugars, their inhibition activity arises from the protonated endocyclic nitrogen, at physiological pH, which leads to strong electrostatic interactions with the carboxylate ion located in the active site of the enzyme. In order to find new treatments for the severe pathologies originated by a malfunction of the above sugar processing enzymes, many synthetic monosaccharidic iminosugar have been prepared over the last four decades. However, also designed and synthetized were less conventional derivatives such as the imminosugar clusters and the imino-disaccharides and -oligosaccharides. While the former class of compound has been extensively reviewed, only two review articles and a book's chapter have been dedicated to the latter family of iminosugars, two dealing exclusively with the carbon-linked disaccharides (imino-C-disaccharides, see section 5), the other focused mainly on the synthesis and biological properties of the imino-O-disaccharides (see section 2). The interest in the di- and oligosaccharidic iminosugar, i.e. carbohydrates constituted of an iminosugar moiety linked to one or more sugar units, resides in their expected stronger and more selective glycosidases inhibition. Indeed, these enzymes are not totally selective for the monosaccharide (e.g. D-glucose, D-mannose, etc.) and the anomeric linkage (α] or β) to be cleaved, and thus also the iminosugar-based inhibitors are poorly selective and scarcely used in therapy. Nevertheless, many glycosidases are endowed with some aglycon specificity, i.e. they selectively recognize the sugar(s) linked to the monosaccharide to be hydrolysed. Therefore, compounds bearing a mimic of the glycon hydrolysis intermediate (the iminosugar) and a natural mono- or ol