Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California , Los Angeles, California 90089, United States.
J Am Chem Soc. 2014 Jul 23;136(29):10418-31. doi: 10.1021/ja504376u. Epub 2014 Jul 9.
The introduction of the CF3 group on the C9 atom in quinidine can significantly increase the conformational interconversion barrier of the cinchona alkaloid scaffold. With this modification the conformational behavior of cinchona alkaloids in various solvents can be conveniently investigated via (19)F NMR spectroscopy. Based on the reliable conformational distribution information obtained, the accuracy of both theoretical (PCM) and empirical (Kamlet-Taft) solvation models has been assessed using linear free energy relationship methods. The empirical solvation model was found to provide accurate prediction of solvent effects, while PCM demonstrated a relatively low reliability in the present study. Utilizing similar empirical solvation models along with Karplus-type equations, the conformational behavior of quinidine and 9-epi-quinidine has also been investigated. A model SN2 reaction has been presented to reveal the important role of solvent-induced conformational behavior of cinchona alkaloids in their reactivity.
在奎尼丁的 C9 原子上引入 CF3 基团可以显著增加金鸡纳生物碱支架的构象互变能垒。通过这种修饰，可以方便地通过 19F NMR 光谱研究各种溶剂中金鸡纳生物碱的构象行为。基于获得的可靠构象分布信息，使用线性自由能关系方法评估了理论（PCM）和经验（Kamlet-Taft）溶剂化模型的准确性。结果表明，经验溶剂化模型能够准确预测溶剂效应，而 PCM 在本研究中可靠性相对较低。利用类似的经验溶剂化模型以及 Karplus 型方程，还研究了奎尼丁和 9-表奎尼丁的构象行为。提出了一个 SN2 反应模型，揭示了溶剂诱导的金鸡纳生物碱构象行为在其反应性中的重要作用。
