title: 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-imidazole CCR-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.
authors.affiliation: Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 - S3, B-9000 Gent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Kuppens
authors.forename: Wouter
authors.initials: W
authors.lastname: Herrebout
authors.forename: Benjamin
authors.initials: B
authors.lastname: Van Der Veken
authors.forename: David
authors.initials: D
authors.lastname: Corens
authors.forename: Alex
authors.initials: A
authors.lastname: De Groot
authors.forename: Julien
authors.initials: J
authors.lastname: Doyon
authors.forename: Guy
authors.initials: G
authors.lastname: Van Lommen
authors.forename: Patrick
authors.initials: P
authors.lastname: Bultinck
mesh_terms: D002942:Circular Dichroism / Q000379:methods*; D003198:Computer Simulation; D005031:Ethylenethiourea / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D011355:Prodrugs / Q000032:analysis* / Q000737:chemistry; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D012399:Rotation; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
chemical_list: D011355:Prodrugs; D019707:Receptors, Chemokine; D005031:Ethylenethiourea; C077232:2-mercaptoimidazole