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 o f 4-deoxy-4-fluoro-D-glucose (4FG) and 6-deoxy-6-fluoro-D-galactose (6 FGA) in methanol-d(4), DMSO-d(6), acetone-d(6) and D2O solution are re ported. Computer analysis of the ABMX spectra of the CH-CH2F fragments gives accurate vicinal HH and HF coupling constants. An iterative com putational analysis of the observed vicinal couplings in this fragment for 6FG, 6FGA and other molecules allows the determination of both th e individual rotamer couplings and the rotamer populations. Considerat ion of the derived rotamer couplings strongly suggests that the correc t assignment for the prochiral C-6 methylene protons in 6FG is that wi th the 6S proton having the larger coupling to H-5. This is the revers e of the assignment of these protons in D-glucose. In contrast, the as signment 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 popul ations. For 6FGA the rotamer in which the fluorine is antiperiplanar t o C-4 is particularly favoured. For 4FG the rotamer with OH anti-perip lanar to the ring O is highly unfavoured, but the other two rotamers a re of almost equal energy. Consideration of the effect of replacing hy droxyl by fluorine in these molecules indicates that any hydrogen bond ing involving the C-4 or C-6 hydroxyls plays little part in determinin g the conformer energies of glucose or galactose in polar solutions.