CONFORMATIONAL-ANALYSIS .20. CONFORMATIONAL-ANALYSIS OF 4-DEOXY-4-FLUORO-D-GLUCOSE AND 6-DEOXY-6-FLUORO-D-GALACTOSE IN SOLUTION

The H-1 and F-19 NMR spectra of the alpha- and beta-pyranose anomers of 4-deoxy-4-fluoro-D-glucose (4FG) and 6-deoxy-6-fluoro-D-galactose (6FGA) in methanol-d(4), DMSO-d(6), acetone-d(6) and D2O solution are reported. Computer analysis of the ABMX spectra of the CH-CH2F fragments gives accurate vicinal HH and HF coupling constants. An iterative computational analysis of the observed vicinal couplings in this fragment for 6FG, 6FGA and other molecules allows the determination of both the individual rotamer couplings and the rotamer populations. Consideration of the derived rotamer couplings strongly suggests that the correct assignment for the prochiral C-6 methylene protons in 6FG is that with the 6S proton having the larger coupling to H-5. This is the reverse of the assignment of these protons in D-glucose. In contrast, the assignment of these protons in 6FGA follows that given previously for D-galactose. The relative energies for the conformations about the C-5-C-6 bond for 4FG, 6FG and 6FGA are given from the derived rotamer populations. For 6FGA the rotamer in which the fluorine is antiperiplanar to C-4 is particularly favoured. For 4FG the rotamer with OH anti-periplanar to the ring O is highly unfavoured, but the other two rotamers are of almost equal energy. Consideration of the effect of replacing hydroxyl by fluorine in these molecules indicates that any hydrogen bonding involving the C-4 or C-6 hydroxyls plays little part in determining the conformer energies of glucose or galactose in polar solutions.