In pursuit of larger lipophilicity enhancement: an investigation of sugar deoxychlorination.

ABSTRACT: The excessive hydrophilicity of carbohydrates hampers their application in drug discovery. Deoxyfluorination is one of the strategies to increase sugar lipophilicity. However, lipophilicities of dideoxy-difluorinated monosaccharides are still well below the desired range for oral drug candidates. Here we investigate the power of deoxychlorination to increase sugar lipophilicities. A series of dideoxygenated chloro-fluorosugars was synthesized and for these substrates it was shown that deoxychlorination increased the log P by an average of 1.37 log P units, compared to 0.83 log P units for analogous deoxyfluorination. This shows the potential of deoxychlorination of carbohydrates to increase lipophilicity while limiting the number of potentially important hydrogen bond

SUBMITTER: Van De Velde J 

PROVIDER: S-EPMC11811696 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature