Application of pH‐zone‐refining countercurrent chromatography in the chiral separation of two β‐adrenergic blocking agents

Abstract

Two β-adrenergic blocking agents, 1-[(1-methylethyl)amino]-3-phenoxy-2-propanol (1) and 1-[(1-methylethyl)amino]-3-(3-methylphenoxy)-2-propanol (2; Toliprolol), were enantioseparated by pH-zone-refining countercurrent chromatography. A two-phase solvent system composed of chloroform containing 0.10 mol/L of di-n-hexyl l-tartrate/0.10 mol/L of boric acid aqueous solution (1:1, v/v) was selected, in which 20 mmol/L triethylamine was added in the organic phase as a retainer and 2 mmol/L HCl was added in the aqueous phase as an eluter. Fifty milligrams of each racemate was completely enantioseparated by pH-zone-refining countercurrent chromatography to yield each enantiomer with a purity of more than 98%, and the recovery of each separated enantiomer reached around 76-82%.

Large‐scale separation of acetylcholinesterase inhibitors from Zanthoxylum nitidum by pH‐zone‐refining counter‐current chromatography target‐guided by ultrafiltration high‐performance liquid chromatography with ultraviolet and mass spectrometry screening

“…In recent years, numerous studies have reported the successful application of UF‐LC‐MS in the screening and identification of bioactive compounds from complex natural products . As for preparative separation method, pH‐zone‐refining CCC, which is derived from the conventional high‐speed counter‐current chromatography (HSCCC), enables the separation of organic acids and alkaloids into a succession of highly concentrated rectangular peaks that elute according to their pKa values and hydrophobicities . Compared with HSCCC, pH‐zone‐refining CCC extends the capability of CCC in various ways including over ten fold sample loading capacity, higher concentration and purity of fractions.…”

Counter‐current chromatography melamine‐modified column and its separation mechanism

“…As we all know, relying on its advantage in its unique separation mechanism and high sample loading, CCC has unique merits in the preparative separation of chiral compounds when the suitable chiral ligand was screened as the solvent additive . If a suitable chiral ligand was screened as functional modifier, this work may provide another potential approach to prepare a chiral CCC column and use it for separating chiral compounds with high throughput, which could avoid the extra step to remove the chiral ligand from the chiral monomeric compounds.…”