Shi Shuai-Hua, Wang Xiao-Juan, Gao Yuan-Yuan, Wang Tao, Wang Chun-Yu, Wang Zi, Wang Qiang, Li Fei, Li Gao-Wei
School of Petrochemical Engineering, Liaoning Petrochemical University, Fushun 113001, China.
College of Chemistry and Chemical Engineering, Henan Engineering Research Center for Green Synthesis of Pharmaceuticals, Shangqiu Normal University, Shangqiu 476000, China.
Anal Chem. 2025 Jan 28;97(3):1900-1908. doi: 10.1021/acs.analchem.4c06024. Epub 2025 Jan 14.
Chiral discrimination is an indispensable tool that has pivotal importance in the assignment of absolute configuration and determination of enantiomeric excess in chiral compounds. A series of enantiomerically pure -1,2-diaminocyclohexane (-DACH)-derived benzamides were first synthesized by simple chemical steps, and 14 variated derivatives have been assessed as NMR chiral solvating agents (CSAs) for discrimination of the signals of mandelic acid (MA) in H NMR analysis. The highly efficient chiral recognition of CSA on different substrates, including MAs, carboxylic acids, amino acid derivatives, and phosphoric acids (32 examples), was expanded via H, F, and P NMR spectroscopy. The quality of enantiodiscrimination was evaluated by means of the enantioresolution parameter . Single-crystal X-ray analysis of three derivatives , , and helped to understand enantiomeric recognition for the promising NMR analysis. Interestingly, the NMR signals of nonequivalent protons between the and configurations were completely opposite in the presence of CSA and its stereoisomer, which can be utilized to establish a straightforward method for the configuration assignment of diverse hydroxy acid substrates.
手性识别是一种不可或缺的工具，在手性化合物的绝对构型确定和对映体过量测定中具有至关重要的意义。首先通过简单的化学步骤合成了一系列对映体纯的 -1,2-二氨基环己烷（-DACH）衍生的苯甲酰胺，并评估了14种变体衍生物作为核磁共振手性溶剂化剂（CSA），用于在氢核磁共振分析中区分扁桃酸（MA）的信号。通过氢、氟和磷核磁共振光谱扩展了CSA对不同底物（包括扁桃酸、羧酸、氨基酸衍生物和磷酸，共32个例子）的高效手性识别。通过对映体拆分参数评估对映体识别的质量。对三种衍生物 、 和 进行单晶X射线分析有助于理解对有前景的核磁共振分析的对映体识别。有趣的是，在CSA 及其立体异构体存在下， 和 构型之间不等价质子的核磁共振信号完全相反，这可用于建立一种直接的方法来确定各种羟基酸底物的构型。
