Glycopeptide antibiotics, chiral selectors

Glycopeptide antibiotics have successfully been used as chiral selectors to resolve the enantiomers of a variety of chiral compounds by means of both chromatographic and electrophoretic techniques. The idea of testing glycopeptide antibiotics as chiral selectors was first introduced by Armstrong and coworkers, at the Pittsburgh Conference in 1994. 

Non steroidal antiinflammatory drugs were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], ristocetin A [33] CSPs under RPmode systems, and on avoparcin CSP under NP mode systems [37]. The enantioresolution of a variety of pro fens was later reported on commercially available vancomycin CSPs [128, 168], and recently on a ME-TAG CSP [58]. Ibuprofen enantiomers were also separated on a CDP-1-containing CSP [55]. Glycopeptide A-40,926 CSP was successfully employed in the analytical and semipreparative separation of 2-arylpropionic acids [63]. 

The use of macrocyclic antibiotics as chiral selectors for HPLC was first proposed by Armstrong et al. [50] in 1994. The most successful of the CSPs are based on the glycopeptide antibiotics vancomycin, teicoplanin and ristocetin A and are commercially available through Advanced Separation Technologies Inc. (Astec Inc.) as Chirobiotic V , Chirobiotic 1 and Chirobiotic R , respectively. More recently, a number of other derivatives of these antibiotics have also been developed offering different stereoselectivities. A comprehensive handbook is now available from Astec Inc. [51 ] alongside a number of recent review articles... 

Fanah S., Cartoni C., Desiderio C., Chiral separation of newly synthesized arylpropionic acids by capillary electrophoresis using cyclodextrins or a glycopeptide antibiotic as chiral selectors. Chromatographia, 54, 87-92 (2001). 

Since first demonstration in 1994 of the potential use of macrocyclic antibiotics as chiral selectors in analysis, glycopeptide antibiotics have been successfully applied for enantiomer separations by liquid chromatography, as recognition components of chiral stationary phases, and by capillary electrophoresis (CE) as soluble chiral selec-tors. Four chiral stationary phases for chromatography with the selectors vancomycin, ristocetin, teicoplanin, and the teicoplanin aglycone are commercialized under the trade name Chirobiotic by Astec and Supelco. Various aspects of analytical applications of glycopeptide antibiotics have been extensively covered in the recent reviews cited above. As an example. Table 2 shows some representative results for CE enantioseparations with vancomycin, ristocetin A, and teicoplanin, which were taken from Ref. 39. 

Table 2 CE enantioseparations with glycopeptide antibiotics as chiral selectors (0.1 M phosphate buffe, pH 6.0, containing 2mM antibiotic). ...

This relatively new class of CSPs incorporates glycopeptides attached covalently to silica gel. These CSPs can be used in the normal phase, reversed phase, and polar organic modes in LC [62]. Various functional groups on the macrocyclic antibiotic molecule provide opportunities for tt-tt complexation, hydrogen bonding, and steric interactions between the analyte and the chiral selector. Association of the analyte... 

Vancomycin was one of the most employed chiral selectors for separating acidic compounds. Introduced by Armstrong et al. for the separation of a wide range of compounds, vancomycin is a glycopeptide antibiotic that contains numerous... 

The chiral recognition mechanisms in NLC and NCE devices are similar to conventional liquid chromatography and capillary electrophoresis with chiral mobile phase additives. It is important to note here that, to date, no chiral stationary phase has been developed in microfluidic devices. As discussed above polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, proteins, crown ethers, ligand exchangers, and Pirkle s type molecules are the most commonly used chiral selectors. These compounds... 

There are literally hundreds of glycopeptide antibiotics, from which vancomycin, teicoplanin, and subsequently risuxretin A (for structures see Fig. 9.18) have been commercialized by Astec as Chirobiotic V, ChiiX)biotic T. and Chirobiotic R. More recently, avoparcin (see Fig. 9.18) has also been successfully applied as a chiral selector [280],... 

As in the case of chromatography, a chiral selector is also required in CE for enantiomeric resolution. Generally, suitable chiral compounds are used in the background electrolyte (BGE) as additives and hence are called chiral selectors or chiral BGE additives. There are only a few publications available that deal with the chiral resolution on a capillary coated with the chiral selector in CE. The analysis of the chiral pollutants discussed in this chapter is restricted only to using chiral selectors in the BGE. The most commonly used chiral BGE additives are cyclo-dextrins, macrocyclic glycopeptide antibiotics, proteins, crown ethers, ligand exchangers, and alkaloids.A list of these chiral BGE additives is presented in Table 1. 

UV transparent and therefore for such type of applications, electrochemical and mass spectrometry are the best detectors. Some of the chiral selectors, such as proteins and macrocyclic glycopeptide antibiotics, are UV-absorb-ing in nature and hence the detection of enantiomers becomes poor. 

Tesarova and Bosakova [58] proposed an HPLC method for the enantio-selective separation of some phenothiazine and benzodiazepine derivatives on six different chiral stationary phases (CSPs). These selected CSPs, with respect to the structure of the separated compounds, were either based on b-CD chiral selectors (underivatized (J>-CD and hydroxypropyl ether (3-CD) or on macrocyclic antibiotics (vancomycin, teicoplanin, teicoplanin aglycon and ristocetin A). Measurements were carried out in a reversed-phase separation mode. The influence of mobile phase composition on retention and enantio-selective separation was studied. Enantioselective separation of phenothiazine derivatives, including levopromazine (LPZ), promethazine and thioridazine, was relatively difficult to achieve, but it was at least partly successful with both types of CSPs used in this work (CD-based and glycopeptide-based CSP), except for levomepromazine for which only the [CCD-based CSP was suitable. 

Glycopeptide antibiotics have been found to be very effective chiral selectors in the enantiomeric separation of racemic pharmaceutical compounds. Vancomycin, ristocetin A, rifamycins, teicoplanin, kanamycin, streptomycin, and avoparcin have been added to the running buffer to obtain enantioseparation (161,203— 207). A few technical modifications, such as coated capillaries and separation conditions in the reverse polarity mode (as opposed to normal polarity mode, where the flow is from anode to cathode) were found to improve sensitivity and increase efficiency (116,208). 

Figure 4.16 Chemical structures of the macrocyclic glycopeptide antibiotics (a) vancomycin, (b) teicoplanin, (c) avoparcin, (d) ristocetin A, that have been used as chiral selectors in CSPs for HPLC. Reproduced from Ward and Farris, J. Chromatogr. A 906 (2001), copyright (2001), with permission from Elsevier.

Like glycopeptide antibiotics, rifamycins were tested as chiral selectors in liquid chromatography and but... 

Macrocyclic glycopeptides are antibiotics produced by different bacterial strains (Table 1) to inhibit the growth of bacterial competitors. These molecules can target specifically the terminal o-Ala-o-Ala sequence of a protein essential to Grampositive cell wall building [1]. Not surprisingly, these molecules were found to be excellent chiral selectors in discriminating between amino acid enantiomers [1, 2, 8, 11-14]. 

Much of what has been learned about the mechanism and binding interactions of the glycopeptides as antibiotics can also be applied to understanding the mechanism of the glycopeptides as chiral selectors. Extensive NMR studies have shown that vancomycin forms back-to-back dimers in solution [13, 18, 19]. As previously discussed, the glycopeptide antimicrobial mechanism has been examined with respect to the role the sugar moiety plays in this process as well as the glycopeptide s ability to dimerize [14,19]. Subsequently, dimerization of vancomycin in chiral separations was examined to determine its impact on enantioselectivity. 

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