title: HPLC Separation of Diastereomers: Chiral Molecular Tools Useful for the Preparation of Enantiopure Compounds and Simultaneous Determination of Their Absolute Configurations.
abstract: To obtain enantiopure compounds, the so-called chiral high performance liquid chromatography (HPLC) method, i.e., HPLC using a chiral stationary phase, is very useful, as reviewed in the present Special Issue. On the other hand, normal HPLC (on silica gel) separation of diastereomers is also useful for the preparation of enantiopure compounds and also for the simultaneous determination of their absolute configurations (ACs). The author and coworkers have developed some chiral molecular tools, e.g., camphorsultam dichlorophthalic acid (CSDP acid), 2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid), and others suitable for this purpose. For example, a racemic alcohol is esterified with (S)-(+)-MαNP acid, yielding diastereomeric esters, which are easily separable by HPLC on silica gel. The ACs of the obtained enantiopure MαNP esters can be determined by the ¹H-NMR diamagnetic anisotropy method. In addition, MαNP or CSDP esters have a high probability of giving single crystals suitable for X-ray crystallography. From the X-ray Oak Ridge thermal ellipsoid plot (ORTEP) drawing, the AC of the alcohol part can be unambiguously determined because the AC of the acid part is already known. The hydrolysis of MαNP or CSDP esters yields enantiopure alcohols with the established ACs. The mechanism and application examples of these methods are explained.
authors: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai 980-8577, Japan. n2harada@tagen.tohoku.ac.jp.
authors: Nobuyuki
authors: N
authors: Harada
mesh_terms: D016880:Anisotropy; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry*; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D058428:Silica Gel; D013237:Stereoisomerism
chemical_list: D004952:Esters; D058428:Silica Gel
keywords: 1H-NMR diamagnetic anisotropy; HPLC separation on silica gel; X-ray crystallography; absolute configuration; chiral molecule; diastereomers; internal reference of absolute configuration