Chiral separation of brompheniramine enantiomers by recycling high‐speed countercurrent chromatography using carboxymethyl‐β‐cyclodextrin as a chiral selector

Abstract

A recycling high-speed countercurrent chromatography protocol was proposed for the enantioseparation of brompheniramine by employing β-cyclodextrin derivatives as a chiral selector. The two-phase solvent system of n-hexane/isobutyl acetate/0.10 mol/L phosphate buffer solution with a volume ratio of 2:4:6 was selected by a series of extraction experiments. Factors that affected the distribution of the enantiomers over the two-phase system (e.g., the type and concentration of β-cyclodextrin derivatives = pH value of the aqueous solution, and the separation temperature) were also investigated. In addition, the theory of thermodynamics is applied to verify the feasibility of the enantioseparation process and the corresponding results demonstrate that this separation process is feasible. The optimized conditions include carboxymethyl-β-cyclodextrin concentration of 0.010 mol/L, pH of 7.5, and temperature of 5°C. Under the optimal conditions, the purities of both monomer molecules were over 99%, and the recovery yields were 88% for (+)-brompheniramine and 85% for (-)-brompheniramine, respectively.

Separation of six compounds including two n‐butyrophenone isomers and two stibene isomers from Rheum tanguticum Maxim by recycling high speed counter‐current chromatography and preparative high‐performance liquid chromatography

“…Aiming to realize a separation among intractable compounds in repeated HSCCC procedures, recycling elution mode has been confirmed to be a practical mean of separating components which have some differences in distribution coefficient [18][19][20][21][22][23][24][25]. While, this methodology takes a long time, but has almost the same solvent consumption and separated volume.…”

“…For isomers with similar polarity and structures, recycling HSCCC has been confirmed to be a practical mean of separating components which have some differences in distribution coefficient. There have been eight reports on separation of isomers by recycling HSCCC in the latest 5 years [18][19][20][21][22][23][24][25]. However, chiral selector was introduced in these reports.…”

Stereoselective separation of (1S, 4S)‐sertraline from medicinal reaction mixtures by countercurrent chromatography with hydroxypropyl‐β‐cyclodextrin as stereoselective selector

“…Because of its unique characteristics, CCC plays an important role in the preparation and separation of isomers . In the past decade, increasing number of papers about chiral separations by CCC has been published . Recycling elution mode was usually employed to improve enantioseparation in various chromatographic methods .…”

Screening and separation of α‐amylase inhibitors from Solanum nigrum with amylase‐functionalized magnetic graphene oxide combined with high‐speed counter‐current chromatography

“…Up to now, the development of new separation analytical method has prompted the discovery of active components in Traditional Chinese medicines. For instance, hyphenated techniques and high‐speed counter‐current chromatography (HSCCC) target separation method greatly improved the separation efficiency .…”