Préparation et évaluation des propriétés physico-chimiques d'hexopyranoses et hexitols fluorés

Authors: Lainé, Danny
Advisor: Giguère, Denis
Abstract: Carbohydrates are an essential class of molecules for living organisms. Besides serving as both a major energy source and structural component, they are also involved in numerous biochemical processes of interest for the pharmaceutical industry, such as molecular recognition. However, native carbohydrates are highly polar molecules having poor pharmacokinetic properties. Therefore, glycomimetic compounds are being developed to tackle this problem. Deoxyfluorination of carbohydrates has emerged as a popular approach to generate glycomimetic tools since the presence of fluorine on organic compounds can leadto molecules with unique properties. Nevertheless, stereo selective syntheses of fluorinated carbohydrates can be quite challenging, especially if there is more than one fluorine incorporated into the carbohydrate scaffold. To bring our own contribution to the field of fluorinated carbohydrates, we proposed new synthetic pathways to prepare 3-deoxy-3-fluoro and 4-deoxy-4-fluoro analogues of D-galactopyranose. The alternative procedures to the decade-long known methods use a chiron approach starting from affordable levoglucosan. These fluorinated galactosides were evaluated as lectin inhibitors and investigated as antiproliferative agents. Following this work, levoglucosan was further used to study the impact of fluorine on the physicochemical properties of carbohydrates. Thus, the preparations of various polyfluorinated compounds such as trifluorinated derivatives of mannose and talose as well as multiple fluorohexitols, are described in this thesis. Lipophilicity of all fluorinated carbohydrates reported in this document has been assessed. In addition, the conformation of some new compounds has been determined both by NMR spectroscopy and by X-ray crystallographic analyses. Moreover, a simple synthetic approach using triethylamine trihydrofluoride (Et3N.3HF) was developed as an alternative to the diethylaminosulfur trifluoride (DAST) reagent. These results highlightthe effect of the fluorine on physical properties of carbohydrates. Furthermore, the different studies could provide tools to help expand research in glycobiology and related fields.
Document Type: Thèse de doctorat
Issue Date: 2022
Open Access Date: 13 June 2022
Grantor: Université Laval
Collection:Thèses et mémoires

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