Epoxide and aziridine derivatives of glycal and carbaglycal systems as useful tools in glycochemistry and automated synthesis of mannose oligosaccharides

This thesis deals with the reactivity and synthetic use of glycal-derived vinyl epoxides, vinyl aziridines and corresponding carba analogs. This new building blocks have been used for the synthesis of new glycoconjugate-Ruthenium complexes, 2,5-disubstituted-2,5-dihydrofurans, 4-aminoglycals and 4-aminocarbaglycal. Carbapyranose 1,2-epoxides were synthesized and their regio- and stereochemical behaviour examined, particularly with O-nucleophiles and ionic liquids as coordinating solvents. Whereas epoxide β turned out to give highly or completely anti-1,2-regio- and stereoselective addition reactions, epoxide α showed a high anti-1,2-regioselectivity which makes this epoxide an effective candidate for the synthesis of carbaoligosaccharides. Furthermore, in this thesis, the synthesis of pseudo-1,2-α-mannobioside, characterized by the presence of a real carbamannose unit, were performed. These compounds showed a good DC-SIGN binding profile, comparable to that of the minimal epitope. In the newly synthetized pseudodisaccharides the non reducing portion of the natural disaccharide Manα1-2Man is replaced by a real D-carbamannose unit with a lipophilic motif, in view of an improved drug-like character of the resulting glycomimetics compared to natural carbohydrates. The binding profile and DC-SIGN inhibitor activity of the new glycoconjugates has been evaluated by Surface Plasmon Resonance (SPR) by Professor Frank Fieschi group (IBS-Institut de Biologie Structurale-Jean Pierre Ebel in Grenoble, France). In conclusion, the target non-reducing end fragments of (Man)9(GlcNAc)2 have been successfully synthesized by the automation glycan assembly under the supervision of Prof. Seeberger at the Max Planck Institute (Potsdam). The AGA approach was chosen to make use of multiple sequential glycosylation with one or two different mannose building blocks that have been appropiately synthesized. Applications of these defined oligosaccharide products as biological probes, for the construction of novel materials, and for the study of their conformational behavior are currently being pursued.