Glycopeptide antibiotics, chiral

Aboul-Enein, H. and Ali, I. (2002) Optimization Strategies for HPLC Enantioseparation of Racemic Drugs Using Polysaccharides and Macrocyclic Glycopeptide Antibiotic Chiral Stationary Phases, Farmaco 57, 513-529. 

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... 

Staroverov, S.M. et al.. New chiral stationary phase with macrocyclic glycopeptide antibiotic eremomycin chemically bonded to sihca, J. Chromatogr. A, 1108, 263, 2006. 

Petrusevska, K. et al.. Chromatographic enantioseparation of amino acids using a new chiral stationary phase based on a macrocyclic glycopeptide antibiotic, J. Sep. ScL, 29, 1447, 2006. 

D Acquarica, I. et al.. Application of a new chiral stationary phase containing the glycopeptide antibiotic A-40,926 in the direct chromatographic resolution of P-amino acids. Tetrahedron Asymmetry, 11, 2375, 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... 

Macrocyclic Glycopeptide Antibiotics-Based Chiral Stationary Phases... 

The most popular and commonly used chiral stationary phases (CSPs) are polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ether based. The art of the chiral resolution on these CSPs has been discussed in detail in Chapters 2-8, respectively. Apart from these CSPs, the chiral resolutions of some racemic compounds have also been reported on other CSPs containing different chiral molecules and polymers. These other types of CSP are based on the use of chiral molecules such as alkaloids, amides, amines, acids, and synthetic polymers. These CSPs have proved to be very useful for the chiral resolutions due to some specific requirements. Moreover, the chiral resolution can be predicted on the CSPs obtained by the molecular imprinted techniques. The chiral resolution on these miscellaneous CSPs using liquid chromatography is discussed in this chapter. 

Although the macrocyclic glycopeptide antibiotic CSPs are very effective for the chiral resolution of many racemic compounds, their use as chiral mobile phase additives is very limited. Only a few reports are available on this mode of chiral resolution. It is interesting to note that these antibiotics absorb UV radiation therefore, the use of these antibiotics as the CMPAs is restricted. However, Armstrong et al. used vancomycin as the CMPA for the chiral resolution of amino acids by thin-layer chromatography, which will be discussed in Section 10.7. 

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],... 

The group of Bakhtiar [57-59] described the chiral bioanalysis of MPH in various matrices, utilizing a number of sample pretreatment strategies, separation on a Chirobiotic V columns, and the use of positive-ion APCI-MS in SRM mode. The chiral selectivity of the Chirobiotic V column is based on the use of the macrocyclic glycopeptide antibiotic vancomycin. The column can be used in both aqueous and organic mobile phase. 

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. 

Rundlet, K.L. Gasper, M.P. Zhou, E.Y. Armstrong, D.W. Capillary electrophoretic enantiomeric separations using the glycopeptide antibiotic, teicoplanin. Chirality 1996, 8, 88-107. 

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). 

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). 

Biaryl structures are wide-spread in many of naturally occuring products including alkaloids, lignans, terpenes, flavonoids, tannins, as well as polyketides, coumarins, peptides, glycopeptides, etc. For example, vancomycin (1) is a basic structure of several related glycopeptide antibiotics [1] balhimycin, actinoidin A, ristocetin A, teicoplanin A2-2, complestatin, etc which are important in medicinal chemistry or as a HPLC chiral stationary phases (vancomycin) [2]. 

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.

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). ...

Figure 7 Structures of chiral drugs determined with electrodes based on glycopeptide antibiotics.

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