Kuppens Tom, Herrebout Wouter, Van Der Veken Benjamin, Corens David, De Groot Alex, Doyon Julien, Van Lommen Guy, Bultinck Patrick
Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 - S3, B-9000 Gent, Belgium.
Chirality. 2006 Aug;18(8):609-20. doi: 10.1002/chir.20297.
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.
使用振动圆二色性确定了强效2-巯基咪唑CCR-2受体拮抗剂JNJ-27553292的两种前体，即1-(3',4'-二氯苯基)-丙醇和1-(3',4'-二氯苯基)-丙胺的绝对构型。因此，拮抗剂本身的绝对构型也得以确定。对这两种前体化合物进行了全面的构象分析，并在B3LYP/cc-pVTZ理论水平上计算了旋转强度。基于这些数据，模拟了振动圆二色性光谱，进而与实验光谱进行比较。光谱之间的一致性使得能够确定绝对构型，这与基于对类似化合物的立体专一反应所提出的构型一致。
