Abstract

The conformational analysis of a series of configurational isomers of 2-(hydroxymethyl)azepan-3,4,5,6-tetrols 1-4 has been carried out. H-1 NMR spectroscopic data, especially vicinal J couplings and nuclear Overhauser enhancements (NOE), assisted by molecular mechanics, molecular dynamics and Monte Carlo calculations, have been used. A fairly good agreement between experimental and calculated data has been found. The different isomers exist in a conformational equilibrium between two chair-like structures. TR-NOE experiments have also allowed us to demonstrate that the bound conformation of compound 2 to the beta-glucosidase from almonds is the major one of this compound present in solution. Finally, molecular docking of the different conformations of these compounds in the binding site of three different enzymes has been performed in order to try to rationalize the observed inhibition of these molecules. (C) Wiley-VCH Verlag GmbH Co.

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