Elucidation of the absolute configuration of JNJ‐27553292, a CCR2 receptor antagonist, by vibrational circular dichroism analysis of two precursors

Abstract The absolute configurations of two precursors, that is, 1‐(3′,4′‐dichlorophenyl)‐propanol and 1‐(3′,4′‐dichlorophenyl)‐propanamine, of a potent 2‐mercapto‐imidazoleCCR‐2 receptor antagonist, JNJ‐27553292, were determined using vibrational circular dichroism. As a consequence, the absolute configuration of the antagonist itself was also determined. The two precursor compounds were subjected to a thorough conformational analysis and rotational strengths were calculated at the B3LYP/cc‐pVTZ level of theory. Based on these data, vibrational circular dichroism spectra were simulated, which in turn were compared with experimental spectra. Agreement between the spectra allowed the assignment of the absolute configuration, which is in agreement with the proposed configuration based on stereospecific reactions on similar compounds. Chirality 18:609–620, 2006. © 2006 Wiley‐Liss, Inc.