The synthesis of 2,2,3,3-Tetrafluorinated Galactose and Glucose derivatives

Abstract

The incorporation of polyfluorinated regions into carbohydrates has been proposed as a strategy to improve the typically low protein–carbohydrate affinity. The creation of a hydrophobic region, while maintaining a potential for attractive dipolar interactions (mediated by the polarised C–F bond) may increase binding affinity.
This thesis describes the synthesis of previously reported 2,3-dideoxy-2,2,3,3-tetrafluorogalactopyranose and 2,3-dideoxytetrafluoroglucopyranose. Further optimisations have been carried out to provide highly efficient and enantioselective routes to both compounds. The synthesis of the novel 2,3-dideoxy-2,2,3,3-tetrafluorogalactofuranose via a modification to the pyranose route has been successfully achieved and optimised. The large scale synthesis of these compounds has enabled their further derivatisation. This has included the development of phosphorylation methodology for 2,2,3,3-tetrafluorogalactose in both pyranose and furanose isomers. The synthesis of the first disaccharides to contain a tetrafluoroethylene moiety has been accomplished, providing tetrafluorinated analogues of known bioactive disaccharides. Studies have also been carried out towards different glycosylation methodologies of 2,2,3,3-tetrafluorinated sugars, enabling access to glycosylation by both electrophilic and nucleophilic reagents. Detailed conformational analysis has been implemented, with the results displaying high similarities between 2,2,3,3-tetrafluorogalactopyranosides and natural non-fluorinated carbohydrates.

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ORCID for Bruno Linclau: orcid.org/0000-0001-8762-0170

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