Carbohydrate-Based Bioactive Compounds for Medicinal Chemistry Applications

L.      Cipolla; F.      Peri

doi:10.2174/138955711793564060

Abstract

In this article we review our work over the years on carbohydrates and carbohydrate mimetics and their applications in medicinal chemistry. In the first part of the review innovative synthetic methods, such as the chemoselective glycosylation method originally developed by our group and its applications to the synthesis of neoglycoconjugates (neoglycopeptides, oligosaccharide mimetics, neoglycolipids, etc … ) will be presented. The high density of functional groups (hydroxyls) on the monosaccharides and the structural role of sugars forming the core of complex glycans in scaffolding and orienting the external sugar units for the interaction with receptors, inspired us and others to use sugars as scaffolds for the construction of pharmacologically active compounds. In the second part of this review, we will present some examples of bioactive and pharmacologically active compounds obtained by decorating monosaccharide scaffolds with pharmacophore groups. Sugar-derived protein ligands were also used as chemical probes to study the interaction of their target with other proteins in the cell. In this context, sugar mimetics and sugar-derived compounds have been employed as tools for exploring biology according to the “chemical genetic” approach.

Keywords: Carbohydrates, glycobiology, glycomimetics, peptidomimetics, glycidic scaffolds, glycoconjugates, medicinal chemistry, glycochemistry, neoglycoconjugates, Sugar-derived protein ligands, cellulose, chitin, glycosylation, influenza virus, Zanamivir, Oseltamivir, Stereoselective cyclisation, Eritoran, lipid-binding protein, benzylamonium lipid, NMR, Chemoselective Ligation, N-Fmoc, N-Boc, ONHMe, NH (OMe), autoimmune syndrome, multiple sclerosis, vitronectin, fibronectin, C-fructoside, Ras Signalling, Surface Plasmon Resonance