Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects
Jacob St‐Gelais, Émilie Côté, Danny Lainé, Paul A. Johnson, Denis Giguère
Abstract
Abstract In this work, we synthesized all mono‐, di‐, and trifluorinated glucopyranose analogues at positions C‐2, C‐3, C‐4, and C‐6. This systematic investigation allowed us to perform direct comparison of 19 F resonances of fluorinated glucose analogues and also to determine their lipophilicities. Compounds with a fluorine atom at C‐6 are usually the most hydrophilic, whereas those with vicinal polyfluorinated motifs are the most lipophilic. Finally, the solvation energies of fluorinated glucose analogues were assessed for the first time by using density functional theory. This method allowed the log P prediction of fluoroglucose analogues, which was comparable to the C log P values obtained from various web‐based programs.