X-ray studies of conformation: observation of conformational polymorphism of a glycoluril clip

Abstract

In order to study the conformational behavior of a glycoluril clip, compound 1 was synthesized and X-ray crystallography, NMR spectroscopy, and molecular modeling were used in the work. The results of the computational studies revealed the stability of the four conformers retained the order aa > as ≈ sa > ss in both gas and solvation models, while solvation decreased the relative energies of each conformer dramatically. In the solid phase, X-ray crystallographic analysis indicated that compound 1 presented conformational polymorphism when it crystallized in various solvents. We fortunately obtained a single crystal of the aa and as conformers of the same glycoluril clip. The X-ray crystallographic analysis in this report provides the first crystallographic evidence of the conformers of a glycoluril clip. Unlike in the solid state, the conformers interconvert rapidly in solution and therefore cannot be detected on the NMR timescale.