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Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects
Author(s) -
StGelais Jacob,
Côté Émilie,
Lainé Danny,
Johnson Paul A.,
Giguère Denis
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002825
Subject(s) - solvation , chemistry , vicinal , fluorine , density functional theory , implicit solvation , computational chemistry , stereochemistry , molecule , organic chemistry
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.