Synthesis, glycosidation and glycosylation of polyfluorinated carbohydrates

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

The synthesis and glycoside formation of polyfluorinated carbohydrates

Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications involving polyfluorinated carbohydrates, here defined as monosaccharides in which more than one carbon has at least one fluorine substituent directly attached to it, with the notable exception of their use as mechanism-based inhibitors. The increasing attention to carbohydrate physical properties, especially around lipophilicity, has resulted in a surge of interest for this class of compounds. This review covers the considerable body of work toward the synthesis of polyfluorinated hexoses, pentoses, ketosugars, and aminosugars including sialic acids and nucleosides. An overview of the current state of the art of their glycosidation is also provided

The synthesis and glycoside formation of polyfluorinated carbohydrates

Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications involving polyfluorinated carbohydrates, here defined as monosaccharides in which more than one carbon has at least one fluorine substituent directly attached to it, with the notable exception of their use as mechanism-based inhibitors. The increasing attention to carbohydrate physical properties, especially around lipophilicity, has resulted in a surge of interest for this class of compounds. This review covers the considerable body of work towards the synthesis of polyfluorinated hexoses, pentoses, ketosugars, and aminosugars including sialic acids and nucleosides. An overview of the current state of the art of their glycosidation is also provided

Glycosylation of vicinal di- and trifluorinated glucose and galactose donors

The acid-catalysed formation of glycosidic bonds is more difficult when glycosyl donors are fluorinated, especially at the 2-position. Here we report high-yielding glycosidation and glycosylation reactions of 2,3-difluorinated- and 2,3,4-trifluorinated gluco- and galactopyranoside donors with a variety of acceptors under conventional trichloroacetimidate/TMSOTf activation in moderate to high anomeric selectivities. This methodology allows access to highly fluorinated glycans, illustrated with the synthesis of a pentafluorinated disaccharide

Chemoenzymatic synthesis of 3-deoxy-3-fluoro-L-fucose and its enzymatic incorporation into glycoconjugates

The first synthesis of 3-deoxy-3-fluoro-L-fucose is presented, which employs a D- to L-sugar translation strategy, and involves an enzymatic oxidation of 3-deoxy-3-fluoro-L-fucitol. Enzymatic activation (FKP) and glycosylation using an a-1,2 and an a-1,3 fucosyltransferase to obtain two fluorinated trisaccharides demonstrates its potential as a novel versatile chemical probe in glycobiology