Selectors glycopeptides

Macrocyclic glycopeptides. The first of these CSPs - based on the cavity of the antibiotic vancomycin bound to silica - was introduced by Armstrong [25]. Two more polycyclic antibiotics teicoplanin and ristocetin A, were also demonstrated later. These selectors are quite rugged and operate adequately in both normal-phase and reversed-phase chromatographic modes. However, only a limited number of such selectors is available, and their cost is rather high. 

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... 

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. 

Only few studies addressed the effect of the silica surface concentration of glycopeptides antibiotics on the chiral performances. The first was performed by Armstrong on a TE CSP toward five racemic test solutes [30]. The study evidenced a modest increase of a and Rs values with increasing the initial selector concentration in the grafting reaction mixture, but no data were reported regarding the effective... 

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]. 

Berthod, A. et al.. Evaluation of the macrocyclic glycopeptide A-40,926 as a high-performance liquid chromatographic chiral selector and comparison with teicoplanin chiral stationary phase, J. Chromatogr. A, 897, 113, 2000. 

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 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... 

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... 

Hui, F. (2004) High Performance Liquid Chromatography and Capillary Electrophoresis Chiral Recognition Mechanisms Using Glycopeptide Macrocyclic Antibiotics as Selectors, Fenxi Huaxue 32, 964-968. 

GLYCOPEPTIDES AS CHIRAL SELECTORS IN CHROMATOGRAPHY AND CAPILLARY ELECTROPHORESIS... 

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. 

The use of CDs for chiral separations has, to date, been the most common approach when using CE or MEKC, so it would be difficult to discuss and detail every aspect relating to their chemistry, effects on separation, and application in this held. The emphasis will, thus, be placed on a short description of the principle and mechanism of chiral separation, typical method development procedures, and an outline of the influential experimental parameters using CE and MEKC. References to recent published review and research literature will enable the reader to explore this vast area further. It is also beyond the scope of this short introductory review to actually outline the actual CE or MEKC separation principles in detail, but an in-depth discussion can be found in this encyclopedia and references to recent textbooks and can be readily found elsewhere. It must, of course, be pointed out that CDs are not the only useful chiral selectors that can be employed using electrophoretic techniques. The use of chiral surfactants (bile salts), crown ethers, metal-chelation agents, carbohydrates, proteins, and glycopeptides have all been used effectively [2]. 

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). 

Liquid Chromatography Stationary phase Amino Acid Derivatives Low-Mass Synthetic Selectors Poly(saccharide) Derivatives Cyclodextrin Derivatives Glycopeptides Metal Chelates Proteins Helical Polymers... 

Chromatography Cyclodextrin Derivatives Glycopeptides Low-Mass Synthetic Selectors Metal Chelates... 

Examples low-mass synthetic selectors, amino acid derivatives, glycopeptides... 

Figure 10.6. Structures of the macrocyclic glycopeptide chiral selectors vancomycin (A) and teicoplanin (B).

Chiral mobile phase additives provide a more versatile and cost-effective approach for enantiomer separations in thin-layer chromatography. Typically, chemically bonded layers with cyclodextrin and its derivatives, bovine serum albumin, or macrocyclic glycopeptides are used as chiral additives in the reversed-phase mode [59,60,172-178]. For [5- and y-cyclodextrins and their derivatives, a 0.1 to 0.5 M aqueous methanol or acetonitrile solution of the chiral selector is used as the mobile phase. Bovine serum albumin is generally used at concentrations of 1-8 % (w/v) in an aqueous acetate buffer of pH 5 to 7 or in a 0.5 M acetic acid solution, in either case with from 3-40 % (v/v) propan-2-ol (or another aliphatic alcohol), added to control retention. Enantioselectivity usually increases with an increase in concentration of the chiral selector, and may be non existent at low concentrations of the chiral selector. 

---