Conformational and Structural Analysis of a ter‐Cyclopentane Scaffold for Molecular Recognition

Well‐defined oligomers of cycloalkanes comprise a relatively unstudied class of organic compounds, and may have general utility in the development of receptors for biologically relevant molecules. We have investigated the solution structure of a ter ‐cyclopentane member of this class by molecular modeling and by NMR spectroscopy. We find that the molecular ensembles derived from conformational searches incorporating NMR‐derived restraints are in excellent qualitative agreement with unrestrained molecular mechanics conformation searches. The ter ‐cyclopentane scaffold adopts an extended rigid conformation, with inter‐ring torsion angles preferentially at 180°. These experiments demonstrate that conformational hypotheses developed in the course of designing ter ‐cyclopentane scaffolds for lipid A recognition are accurate, and furthermore provide support to the broader use of this class of compounds as scaffolds in molecular recognition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)