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Heavily fluorinated carbohydrate and nucleoside analogues
A few years ago, we became interested in heavily fluorinated analogues of biomolecules to probe the relative importance of static and induced dipolar interactions in molecular recognition. We started our project with hypothesis that induced dipolar interactions have larger effect on the chemical potential of solute in aqueous solution in comparison to that of same solute in enzyme active sites or physiological receptors. If this hypothesis is correct, decreasing the polarizability of the a biologically active compound while maintain its electrostatic charge distribution and shape should lead to enhanced binding to appropriate physiological receptors. We call this strategy enhancing “polar hydrophobicity”. With this hypothesis, we designed, prepared, structurally characterized and tested the biological transport properties of the novel fluorinated hexose, 2,3,4-trideoxy-2,3,4-hexafluorohexose analogue. Subsequently, we refined enantioselective synthetic methodology, chiral resolution, and the anomeric activation chemistry of these analogues. As a result, the fluorinated sugar is available in gram quantities (either enantiomer >98% ee) in our laboratories. We have also shown that glycosyl triflate of 1 is useful for anomeric activation. Remarkably glycosidations via the glycosyl triflate were very stereoselective. ^ We have also developed synthetic methodology for 2,3-dideoxy-2,2,3,3-tetrafluororibofuranose and the corresponding nucleosides. ^
Kim, Hongwoo, "Heavily fluorinated carbohydrate and nucleoside analogues" (2000). ETD collection for University of Nebraska - Lincoln. AAI9967381.