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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 19F 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.

Affinity data, such as dissociation constants (KD) or inhibitory concentrations (IC50), are widely used in drug discovery. However, these parameters describe an equilibrium state, which is often not established in vivo due to pharmacokinetic effects and they are therefore not necessarily sufficient for evaluating drug efficacy. More accurate indicators for pharmacological activity are the kinetics of binding processes, as they shed light on the rate of formation of protein–ligand complexes and their half-life. Nonetheless, although highly desirable for medicinal chemistry programs, studies on structure–kinetic relationships (SKR) are still rare. With the recently introduced analytical tool kinITC this situation may change, since not only thermodynamic but also kinetic information of the binding process can be deduced from isothermal titration calorimetry (ITC) experiments. Using kinITC, ITC data of 29 mannosides binding to the bacterial adhesin FimH were re-analyzed to make their binding kinetics accessible. To validate these kinetic data, surface plasmon resonance (SPR) experiments were conducted. The kinetic analysis by kinITC revealed that the nanomolar affinities of the FimH antagonists arise from both (i) an optimized interaction between protein and ligand in the bound state (reduced off-rate constant koff) and (ii) a stabilization of the transition state or a destabilization of the unbound state (increased on-rate constant kon). Based on congeneric ligand modifications and structural input from co-crystal structures, a strong relationship between the formed hydrogen-bond network and koff could be concluded, whereas electrostatic interactions and conformational restrictions upon binding were found to have mainly an impact on kon.

The present invention aims at solving the problems of conventional methods for producing an 18F-labeled compound, that is, the problem of purification of a compound in a liquid phase synthesis method and the problem of an insufficient yield due

The synthesis of all four deoxyfluoro-α-D-glucopyranosyl phosphates is described.Rate conctants for their acid-catalyzed hydrolysis were determined, and fluorine substitution was shown to have a significant effect in lowering the rate, particularly when t

Reaction of 1,6:3,4-dianhydro-β-D-altropyranose (I) with potassium hydrogen fluoride in hot ethylene glycol gave 1,6-anhydro-3-deoxy-3-fluoro-β-D-mannopyranose (II).On acid catalysed hydrolysis or acetolysis of compound II 3-deoxy-3-fluoro-D-mannose (VIII) or its tetra-O-acetyl derivative VII, respectively, were obtained.Reduction of compound VIII with sodium borohydride gave 3-deoxy-3-fluoro-D-mannitol (IX).The structures of the mentioned compounds were proved by 1H NMR spectroscopy.