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.

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

2018

Abstract

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.
2-feb-2018
Italiano
Di Bussolo, Valeria
Bertoli, Alessandra
Cecchetti, Violetta
Lindkvist, Karin
Università degli Studi di Pisa
File in questo prodotto:
File Dimensione Formato  
Ph.D._Thesis_Vittorio_Bordoni.pdf

Open Access dal 06/02/2021

Tipologia: Altro materiale allegato
Dimensione 16.39 MB
Formato Adobe PDF
16.39 MB Adobe PDF Visualizza/Apri
Report_finale.pdf

Open Access dal 06/02/2021

Tipologia: Altro materiale allegato
Dimensione 267.42 kB
Formato Adobe PDF
267.42 kB Adobe PDF Visualizza/Apri

I documenti in UNITESI sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/151422
Il codice NBN di questa tesi è URN:NBN:IT:UNIPI-151422