H-1 NMR study of the conformation and absolute stereochemistry of two spirocyclic NK-1 antagonists

The binding affinities at the human NK-1 receptor of two spirocyclic compounds were found to be similar despite being epimeric at a key stereocentre. This unexpected result prompted a thorough investigation of the solution conformations of the two compounds. This revealed that a conformational switch in the tetrahydrofuran ring enabled the C-3-aryl group to be equatorial in both cases, leading to a similar juxtaposition of the aryl rings. Copyright (c) 2005 John Wiley & Sons, Ltd.