Recent Advances on Chiral Mobile Phase Additives: A Critical Review

Chirality is one of the fundamental attributes of nature, which exists in different or even completely opposite metabolic,toxicological and pharmacological properties in organisms. Consequently, obtaining enantiomerically pure drugs or optically active intermediates is highly desired in many fields like medicine, food and biochemistry. Thereby, it also promoted the development of various enantiomer selective separation techniques. Among the many chiral separation methods, chiral mobile phase additives(CMPAs) are widely used in various chromatographic techniques due to their simple operation,good versatility and low price. There have been a number of reviews on the research progress of CMPAs in last 2 decades,but they only reviewed the application of CMPAs in one specific chromatographic technique. Therefore, to provide a more comprehensive illustration of CMPAs in separation technology, their applications in high-performance liquid chromatography, capillary electrophoresis, countercurrent chromatography, nano-liquid chromatography were summarized and their advantages and disadvantages were briefly introduced in this critical review. The application of molecular simulation in the study of chiral separation mechanism was briefly summarized. We expect that it will provide researchers with the latest developments in this field and potential inspirations.

Enantiomeric separations of four basic drugs containing N-alkyl groups by a RP-HPLC system using SBE-β-CD as chiral mobile phase additive

The chiral separations of four pharmaceutical racemates which contain N-alkyl groups were satisfactorily resolved using SBE-β-CD as a chiral mobile phase additive （CMPA） in a RP-HPLC system （the resolution is 2.701 for ondansetron hydrochloride, 1.996 for sulpiride, 1.293 for clenbuterol hydrochloride and 0.816 for omeprazole）. In addition, the effects of different parameters such as CD type and CD concentration were investigated. The separation mechanism arises through the combination of several potential interactions, including electrostatic interactions as well as hydrogen bonding interactions and hydrophobic inclusion interactions, which allow for the SBE-β-CD-drug complexation with strong stereoselectivity and stability. The resolution also relates to the number and location of N atoms in the enantiomers. This method will be applicable to the isolation of various types of biologically imoortant enantiomers containing N-alkyl groups.

Asymmetric hydroazidation ofα-substituted vinyl ketones catalyzed by chiral primary amine

We report herein the first example of asymmetric hydroazidation of α-substituted vinyl ketones by using chiral primary amines as the catalysts.A simple chiral primary-tertiary diamine catalyst derived from lphenylalanine was found to readily promote this aza-Michael addition reaction with enamine protonation as the key stereogenic step,thus enabling the effective synthesis of α-chiral β-azido ketones with good yields and moderate enantioselectivities.