Glycopeptides enantioseparation

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. 

Sztojkov-lvanov, A. et al., Comparison of separation efficiency of macrocyclic glycopeptide-based chiral stationary phases for the LC enantioseparation of fi-amino acids, Chromatographia, 64, 89, 2006. 

Peter, A. et al., Enantioseparation by HPLC of imino acids on macrocyclic glycopeptide stationary phases and as their (5)-N-(4-nitrophenoxycarbonyl)-phenylalanine methoxyethyl ester derivatives, Chromatographia, 56, S41, 2002. 

Berkecz, R. et al., LC enantioseparation of -lactam and P-amino acid stereoisomers and a comparison of macrocyclic glycopeptide and P-cyclodextrin-based columns, Chromatographia, 63, S37, 2006. 

Wamke, M.M. et al.. Use of native and derivatized cyclodextrin based and macrocychc glycopeptide based chiral stationary phases for the enantioseparation of pterocarpans by HPLC, J. Liq. Chrom. Rel. TechnoL, 28, 823, 2005. 

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. 

TABLE 2-1. Physicochemical Properties of Glycopeptide Antibiotics Used for Enantioseparation... 

Table 2-1). It has to be expected that glycopeptides will establish next to cyclodex-trines for a routine use in enantioseparations. 

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). 

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). ...

There are many classes of CSPs applicable in different mobile-phase modes. In particular, CSPs based on derivatized polysaccharides, native and derivatized cyclodextrins, macrocyclic glycopeptides, and Pirkle-type chiral selectors operate quite well in four separation modes, i.e RP, polar organic phase, NP, and super- or subcritical fluid chromatography (SFC) conditions. It is common that a chiral compound can be separated on the same CSP in more than one separation mode [58, 160, 166, 170-176]. For example, Nutlin-3, a small molecule antagonist of MDM2, has been baseline resolved from its enantiomer in all four mobile-phase conditions (Fig. 16) [170]. Multimodal enantioseparation on the same CSP would be greatly beneflcial for chiral method development in pharmaceutical industry. 

Berthod A, He BL, Beesley TE (2004) Temperature and enantioseparation by macrocyclic glycopeptide chiral stationtiry phases. J Chromatogr A 1060 205-214 Stringham RW, Blackwell JA (1997) Factor that control successful entropically driven chiral separations in SEC and HPLC. Antil Chem 69 1414-1420... 

Sun P, Ktishnan A, Yadav A, MacDonneU FM, Armstrong DW (2008) Enantioseparations of chiral mthenium(II) polypytidyl complexes using HPLC with macrocycUc glycopeptide chiral stationary phases (CSPs). J Mol Struct 890 75-80... 

The macrocyclic glycopeptide chiral selectors are now a very important class of CSPs that must be part of the column set of any laboratory involved in enantiomeric separations. The variety of functionalities found in these relatively small molecules allow for many different interactions leading to successful enantioseparations [29]. The similarities between members of this class of chiral selectors produced the complementary separation property [14, 30, 31]. If a partial separation of an enantiomeric pair is observed on a macrocyclic selector, say vancomycin, a baseline separation may very likely be observed on a different selector, say teicoplanin. This interesting property in method development illustrates the large number of selector-selectand possible interactions. Such complementarities are due to the... 

Ilisz I, Berkecz R, Peter A (2009) Retention mechanism of HPLC enantioseparations on macrocyclic glycopeptide-based chiral stationary phases. J Chromatogr A 1216 1845-1860... 

Beesley TE, Lee JT. Method development and optimization of enantioseparations using macrocyclic glycopeptide chiral stationary phases. In Subramanian G, editor. Chiral separation Ttechniques. A practical Aapproach. edition. Wein-heim Wiley-VCH 2007. p 1-28. 

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