Synthesis of polyfluorinated carbohydrates

Abstract

The impact of deoxyfluorination on fundamental properties of carbohydrates is a large topic of investigation in our group. More precisely, the insertion of polyfluorinated motifs has shown to alter lipophilicity, transport rates across red blood cells, and binding to certain receptors. As large quantities of fluorinated analogues are required for the study of these properties, as well as for other ongoing synthetic projects, convenient syntheses of polyfluorinated carbohydrates on large scale are currently being investigated. This thesis describes the successful synthesis of previously reported 2,3,4-trideoxy-2,3,4-trifluoro-D-glucopyranose and 2,3-dideoxy-2,2,3,3-tetrafluoro-D-glucopyranose.

Regarding the synthesis of the 2,3,4-trifluoroglucose, two different synthetic routes were investigated, both of which starting with the conversion of the commercial and cheap levoglucosan into its trifluorinated counterpart, then subjected to an anomeric hydrolysis procedure developed in our group which afforded the open form of the sugar.

The synthesis of 2,2,3,3-tetrafluoroglucose was achieved via a fluorinated building block approach relying on an intermolecular coupling reaction between D-glyceraldehyde acetonide and the 4-bromo-2,2,3,3-tetraflurorobutene. As this reaction turned out to be the most problematic when repeated in our group, extensive efforts were devoted to its optimization, this include investigation under flash flow conditions, as well as the utilization of a different protected derivative of D-glyceraldehyde.

This thesis also reports the study of intramolecular hydrogen bond (H-bond) interactions in a series levoglucosan derivatives, some of which involve fluorine atoms as H-bond acceptor. Ultimately, this study brought additional evidence of the ability of C-F bonds to compete with better H-bond acceptors such as an oxygen atom.

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

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