Synthesis and conformational analysis of galactose-derived bicyclic scaffolds

Two novel galactose-derived bicyclic acetamides were synthesized. The conformational behavior of these cyclic acetamides in aqueous solution was fully investigated. The NMR spectroscopic data suggests that the pyran ring interconverts between two (4C1, 1S3) or three (4C1, 1S3 and 1C4) conformations and molecular modelling studies allowed the structures' geometries to be defined. Three different force fields were used (Amber*, MM3* and OPLSAA) and fitting procedures were employed to reproduce the experimental 3JH-H coupling constants and NOE contacts. Evaluation of the results established which of these three well-known force fields were the most reliable in reproducing the experimental observations and should therefore be used for analogous design studies. © Wiley-VCH Verlag GmbH & Co. KGaA, 2006.