Vancomycin as a Chiral Selector in Centrifugal Partition Chromatography

Abstract

The use of vancomycin as a chiral selector was introduced by D. W. Armstrong. This macrocyclic antibiotic was used either free in solution for thin-layer chromatography (TLC) and capillary electrophoresis (CE) or covalently bonded to silica gel in the case of high performance liquid chromatography (HPLC). Its possible use in countercurrent chromatography (CCC) or centrifugal partition chromatography (CPC) is also of interest since these techniques have preparative capabilities which make them attractive for multigram scale production of enantiomers. 295Two immiscible liquid phases coexist: an aqueous stationary phase containing vancomycin, and an organic mobile phase in which the racemic compound is more partitioned. This has a number of advantages over HPLC: lower stationary phase costs, ease of recovery of the antibiotic and exchange with a fresh batch, and, especially, improved resolution due to higher selectivity (α).Surprisingly, our experiments showed that chiral recognition in CCC & CPC is strongly solvent-sensitive. Acetonitrile, used by D. W. Armstrong at 10% or higher concentrations, was found to inhibit enantio-selectivity at levels as low as 5%. Inhibition was observed with most solvents, with the notable exception of toluene and related aromatics bearing no other heteroatom than halogens in their molecule. Exceptionally high selectivity factors (α > 30) were observed for dansyl-norleucine in toluene-, ethylbenzene-and hexafluorobenzene-vancomycin 0.1 M (pH 4.7) systems. In a CPC run using toluene, injection of 50 mg dansyl-norleucine led to the isolation of 20.4 mg L isomer ([α] 20 D = -29.8°) and 24.3 mg D isomer ([α]

Enantiomeric separation of (R, S)-naproxen by recycling high speed counter-current chromatography with hydroxypropyl-β-cyclodextrin as chiral selector

“…So far the following nine chiral selectors had been successfully applied in chiral separation by CCC and CPC: cinchona alkaloid derivatives [14,15], N-dodecanoyl-lproline derivatives [16,17], ␤-cyclodextrin derivatives [18][19][20][21], vancomycin [22], cellulose and amylose derivatives [23,24], (+)-(18-crown-6)-tetracarboxylic acid [25], tartaric acid derivatives [20,26,27], (S)-naproxen derivatives [28,29] and fluorinated chiral selectors [30]. In the present study, hydroxypropyl-␤-cyclodextrin (HP-␤-CD) was used as chiral selector for HSCCC separation of (R, S)-naproxen using recycling elution mode.…”

Countercurrent Chromatography, Scope and Perspectives: Application to Chirotechnology

“…In this way, retention of the CS in the stationary phase is ensured under the conditions in which the analyte partitions. The opposite approach is also valid and there are several CS that can be used in the aqueous phase of an organic/aqueous biphasic solvent system [68][69][70].…”

Modelling and optimization of a two phase system for the separation of equol enantiomers by recycling high-speed counter-current chromatography

“…Compared with well-established HPLC enantiomer separation, chiral separation by HSCCC has a larger capacity and avoids the irreversible adsorption onto the solid-supported stationary phase, but it also yields low efficiency due to its relatively low theoretical plates, and the difficulty in finding a good chiral selector (CS). So far, successful applications of the following CSs have been found in the chiral separation by CCC: cinchona alkaloid derivatives; 7,8 N-dodecanoyl-proline derivatives; 9,10 tartaric acid derivatives; [11][12][13][14] vancomycin; 15 cellulose and amylose derivatives; 16 b-cyclodextrin derivatives; [17][18][19] (S)-naproxen derivatives; 20,21 and fluorinated CSs. 22 Generally speaking, HSCCC requires a separation factor greater than 1.40 to resolve two enantiomers completely, but the separation factors of most currently available selectors are generally in the range of 1.01-1.40.…”