Modeling ring puckering in strained systems: application to 3,6-anhydroglycosides

Different conformations of methyl 3,6-anhydroglycosides with the beta-D-galacto, alpha-D-galacto, and beta-D-gluco configurations were studied by molecular mechanics (using the program mm3) and by quantum mechanical (QM) methods at the HF/- and B3LYP/6-31+G** levels, with and without solvent emulation. Using molecular mechanics, the energies were plotted against the phi, theta puckering coordinates of Cremer and Pople. In such strained systems, only two extreme conformations of the six-membered ring are likely: (1)C(4) and B(1,4), or any one close to either of them. Results show the preponderance of a distorted chair conformation over that of the distorted boat, though the energy difference is lower and the distortions are larger for the compound with the beta-D-galacto configuration. For derivatives of this compound, experimental data in solution indicate both chair and boat forms, depending on the compound and the solvent, whereas for the remaining compounds, experimental data always show the preponderance of the chair conformation. The more accurate DFT calculations lead to the lower energy differences, suggesting that HF and MM3 underestimate the stability of the boat-like conformations. Similar studies on model compounds depict the importance of the anomeric effect in the conformational preferences.