Enantioseparation of Racemic Flurbiprofen by Aqueous Two‐Phase Extraction With Binary Chiral Selectors of L‐dioctyl Tartrate and L‐tryptophan

Abstract

A novel method for chiral separation of flurbiprofen enantiomers was developed using aqueous two-phase extraction (ATPE) coupled with biphasic recognition chiral extraction (BRCE). An aqueous two-phase system (ATPS) was used as an extracting solvent which was composed of ethanol (35.0% w/w) and ammonium sulfate (18.0% w/w). The chiral selectors in ATPS for BRCE consideration were L-dioctyl tartrate and L-tryptophan, which were screened from amino acids, β-cyclodextrin derivatives, and L-tartrate esters. Factors such as the amounts of L-dioctyl tartrate and L-tryptophan, pH, flurbiprofen concentration, and the operation temperature were investigated in terms of chiral separation of flurbiprofen enantiomers. The optimum conditions were as follows: L-dioctyl tartrate, 80 mg; L-tryptophan, 40 mg; pH, 4.0; flurbiprofen concentration, 0.10 mmol/L; and temperature, 25 °C. The maximum separation factor α for flurbiprofen enantiomers could reach 2.34. The mechanism of chiral separation of flurbiprofen enantiomers is discussed and studied. The results showed that synergistic extraction has been established by L-dioctyl tartrate and L-tryptophan, which enantioselectively recognized R- and S-enantiomers in top and bottom phases, respectively. Compared to conventional liquid-liquid extraction, ATPE coupled with BRCE possessed higher separation efficiency and enantioselectivity without the use of any other organic solvents. The proposed method is a potential and powerful alternative to conventional extraction for separation of various enantiomers.

Enantioseparation of flurbiprofen enantiomers using chiral ionic liquids by liquid‐liquid extraction

“…In these biphasic resolutions, the influence of the concentrations of the extractants and flurbiprofen enantiomers, the types of organic solvents and extractants, pH and temperature on the biphasic recognition process have been investigated and the enantioselectivity is 1.24 in optimized condition at 25 . Chen et al 35 also developed a method using aqueous two-phase extraction (ATPE) coupled with biphasic recognition chiral extraction to separate flurbiprofen by L-dioctyl tartrate and L-tryptophan and achieved good separation effect.…”

Chiral Ionic Liquids: Structural Diversity, Properties and Applications in Selected Separation Techniques

“…The use of ABS for the resolution of racemates involves two separate strategies. The first is based on the addition of a chiral selector, i.e., β-cyclodextrin derivatives, copper-β-cyclodextrin complexes, tartaric acid derivatives, proteins or microbial cells to ABS formed from a polymer-polymer combination, micellar systems of polar solvents and salts [97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113]. The second method utilizes the addition of one substance that acts simultaneously as a phase former and a chiral selector [114][115][116].…”

The development of biphasic chiral recognition in chiral separation

“…In one work, N‐n‐dodecyl‐L‐proline and Cu(II) ions were added to organic phase together to take the place of tartrate derivatives as lipophilic chiral selector . And in another effort, L‐tryptophan successfully replaced β‐cyclodextrin derivatives as hydrophilic chiral selector The concentrations of the chiral selectors.…”