Determination of Absolute Configurations of Bedaquiline Analogs by Quantum Chemical Electronic Circular Dichroism Calculations and an X-ray Diffraction Study

作者：Wang, Zhiqiang; Zhao, Lixia; Chen, Yu; Xu, Wei; Sun, Tiemin^*

来源：European Journal of Organic Chemistry, 2014, 2014(18): 3814-3821.

DOI：10.1002/ejoc.201400135

• Chirality
• Circular dichroism
• Density functional calculations
• X-ray diffraction
• Medicinal chemistry

Two chiral analogs of bedaquiline were selected from a series of compounds designed as anti-Mycobacterium tuberculosis drugs for synthetic and stereochemical research. The compounds were synthesized from chiral precursors for the first time, and the absolute configurations (ACs) were determined by electronic circular dichroism (ECD) and quantum chemical calculations. Single crystals of both compounds were obtained for X-ray analysis, and the crystal structures and ab initio calculated geometries were extremely similar, which permitted a comparison of the relative reliabilities of ACs obtained by ECD analyses and theoretical simulation. In addition, the in vitro antituberculosis activities of the two compounds were investigated.

• 出版日期2014-6
• 单位沈阳药科大学