Synthesis, glycosidation and glycosylation of polyfluorinated carbohydrates

Abstract

Glycosylation is a ubiquitous process in nature, where glycans are involved in metabolic pathways and recognition events. Thus, fluorinated glycans can act as probes in the investigation of protein-glycan interactions and epitope mapping studies. Currently, most monofluorinated glycans can be made by enzymatic glycosylation of monofluorinated donors. There are no enzymatic glycosylations described with sugar donors having more than 1 fluorine atom in their ring. In carbohydrates, deoxyfluorination was shown to increase chemical stability and reduce their hydrophilicity. Chemical glycosylation of deoxyfluorinated carbohydrates is challenging because the fluorine electron-withdrawing effect destabilises the transition states of anomeric C−O bond-forming reactions. The effect is pronounced when the number of fluorine atoms increases and when they are located adjacent to the anomeric position. To date, there is limited precedence for the chemical glycosylation of polyfluorinated carbohydrates. Most of the glycosylation methods developed involve anomeric alkylation which results in inversion of a stereogenic centre on the acceptor. Most of the methods developed are glycosidation, i.e., involve non-carbohydrate acceptors. This thesis describes our efforts to achieve conventional chemical glycosidation and glycosylation of 2,3-difluoro- and 2,3,4-trifluorinated glucose and galactose donors using trichloroacetimidate pre-activation. Two distinct goals were established: being able to reach full conversion and increasing the anomeric selectivity of the reaction.

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Identifiers

ORCID for Kler Huonnic: orcid.org/0000-0002-8531-2307

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

ORCID for Seung Lee: orcid.org/0000-0002-8598-3303

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