Stereochemical identification of (R)‐ and (S)‐ibuprofen using residual dipolar couplings, NMR, and modeling

In this work, we describe an NMR-based method that utilizes an orientation media composed of the chiral polypeptide liquid crystal poly-γ-benzyl-L-glutamate (PBLG) dissolved in CDCl3, to measure the 1H-1H, 1H-13C and 13C-13C residual dipolar couplings (RDCs) of (R) and (S)-ibuprofen. Calculated RDCs, obtained from the lowest energy conformers, are then compared with the experimentally measured RDCs to predict the stereochemistry of each enantiomer. Excellent agreement between calculated and experimental RDCs was found when the lowest energy structure of each enantiomer, obtained in a simulated PBLG/CDCl3 environment, was used to back-calculate the RDCs. This method is generally useful for small molecular weight molecules that possess either one or two chiral centers, are soluble in low viscosity organic solvents, and will not crystallize (Clegg, Crystal Structure Analysis. Principles and Practice. New York: Oxford University Press; 2002) or cannot be derivatized with a Mosher's reagent (Dale and Mosher, J Am Chem Soc 1973;95:512–519). Chirality, 2006. © 2006 Wiley-Liss, Inc.