药物对映体含量测定的核磁共振法研究Ⅰ．非洛地平

Study of NMR Methods for Stereoisomeric Determination of PharmaceuticalsⅠ. Felodipine

本文报道了在位移试剂Ｅｕ（ＦＯＤ）３、Ｅｕ（ＴＦＣ）３和Ｅｕ（ＨＦＣ）３存在下非洛地平质子信号的镧诱导位移（ＬＩＳ）值，非洛地平的芳氢质子信号得到简化并解析；在手性位移试剂Ｅｕ（ＨＦＣ）３存在下，观察到甲酯的甲基明显的对映体位移差值（△△δ），据此，可对非洛地平直接进行对映体的含量分析。当Ｅｕ（ＨＦＣ）３：非洛地平为０．６２０（摩尔比）时，甲酯甲基的Ｒ和Ｓ对映体两峰的峰谷高度为峰高的３．８％，即当对映体之一的含量不低于３．８％时，可对非洛地平的对映体含量进行精确的直接测定。

The 90MHz 1H NMR spectra of racemic felodipine [4-(2, 3-dichlorophenyl)-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylic acid, ethyl methyl ester), have been studied with the achiral shift reagent, Eu (FOD)3, Ⅰ, and the chiral shift reagent, Eu (TFC)3, Ⅱ, and Eu (HFC)3, Ⅲ. Substantial Lanthanide-Induced Shifts (LIS) were seen for the proton signals of FLDP withⅠ andⅢ, and the aromatic proton signals were simplified. Appreciable enantiomeric shift differences (△△δ) were seen for methyl signal of -COOCH3 usingⅢ that should permit direct determination of enantiomeric excess for samples of FLDP. As little as 3. 8% of a minor enantiomer should be readily detectable.