Marathias Vasilios M, Tawa Gregory J, Goljer Igor, Bach Alvin C
Discovery Analytical Chemistry, Chemical and Screening Sciences, Wyeth Research, Princeton, NJ 08543-8000, USA.
Chirality. 2007 Sep;19(9):741-50. doi: 10.1002/chir.20338.
In this work, we describe an NMR-based method that utilizes an orientation media composed of the chiral polypeptide liquid crystal poly-gamma-benzyl-L-glutamate (PBLG) dissolved in CDCl(3), to measure the (1)H-(1)H, (1)H-(13)C and (13)C-(13)C residual dipolar couplings (RDCs) of (R) and (S)-ibuprofen. Calculated RDCs, obtained from the lowest energy conformers, are then compared with the experimentally measured RDCs to predict the stereochemistry of each enantiomer. Excellent agreement between calculated and experimental RDCs was found when the lowest energy structure of each enantiomer, obtained in a simulated PBLG/CDCl(3) environment, was used to back-calculate the RDCs. This method is generally useful for small molecular weight molecules that possess either one or two chiral centers, are soluble in low viscosity organic solvents, and will not crystallize (Clegg, Crystal Structure Analysis. Principles and Practice. New York: Oxford University Press; 2002) or cannot be derivatized with a Mosher's reagent (Dale and Mosher, J Am Chem Soc 1973;95:512-519).
在本研究中，我们描述了一种基于核磁共振（NMR）的方法，该方法利用由溶解于CDCl₃中的手性多肽液晶聚-γ-苄基-L-谷氨酸（PBLG）组成的取向介质，来测量（R）-和（S）-布洛芬的¹H-¹H、¹H-¹³C和¹³C-¹³C剩余偶极耦合（RDC）。然后将从最低能量构象体获得的计算RDC与实验测量的RDC进行比较，以预测每种对映体的立体化学。当使用在模拟的PBLG/CDCl₃环境中获得的每种对映体的最低能量结构来反算RDC时，发现计算得到的RDC与实验RDC之间具有极好的一致性。该方法通常适用于具有一个或两个手性中心、可溶于低粘度有机溶剂且不会结晶（Clegg，《晶体结构分析：原理与实践》。纽约：牛津大学出版社；2002年）或不能用莫舍尔试剂衍生化的小分子（Dale和Mosher，《美国化学会志》1973年；95：512 - 519）。
