Elucidation of the absolute configuration of JNJ-27553292, a CCR2 receptor antagonist, by vibrational circular dichroism analysis of two precursors.
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.
Kuppens
Tom
T
Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 - S3, B-9000 Gent, Belgium.
Herrebout
Wouter
W
Van Der Veken
Benjamin
B
Corens
David
D
De Groot
Alex
A
Doyon
Julien
J
Van Lommen
Guy
G
Bultinck
Patrick
P
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
D011355:Prodrugs; D019707:Receptors, Chemokine; D005031:Ethylenethiourea; C077232:2-mercaptoimidazole