Enantiomeric glycopeptides

Method Development and Optimization of Enantiomeric Separations Using Macrocyclic Glycopeptide Chiral Stationary Phases... 

Because plasma and urine are both aqueous matrixes, reverse-phase or polar organic mode enantiomeric separations are usually preferred as these approaches usually requires less elaborate sample preparation. Protein-, cyclodextrin-, and macrocyclic glycopeptide-based chiral stationary phases are the most commonly employed CSPs in the reverse phase mode. Also reverse phase and polar organic mode are more compatible mobile phases for mass spectrometers using electrospray ionization. Normal phase enantiomeric separations require more sample preparation (usually with at least one evaporation-to-dryness step). Therefore, normal phase CSPs are only used when a satisfactory enantiomeric separation cannot be obtained in reverse phase or polar organic mode. 

Another factor that remarkably affects the enantioresolution of given enantiomeric pairs has been shown to be the binding chemistry used for the silica immobilization of glycopeptides (see Section 2.2). This was illustrated in the case of ristocetin A, which was covalently bonded to silica microparticles by immobilization onto epoxy-activated silica under mild conditions [22], and compared with the corresponding commercially available CSP, where the macrocycle was immobilized as previously reported for vancomycin, rifamycin B, thiostrepton [7], and teicoplanin [30]. The comparison proved that immobilization of ristocetin A onto epoxy-activated silica could significantly improve the enantioselectivity and the resolution of the corresponding CSP in the separation of a-amino acids under RP conditions [22]. 

Fanah, S., Catarcini, P., and Presutti, C., Enantiomeric separation of acidic compounds of pharmaceutical interest by capillary electrochromatography employing glycopeptide antibiotic stationary phases, J. Chromatogr. A, 994, 227, 2003. 

Fanah, S. et al.. Use of short-end injection capiUary packed with a glycopeptide antibiotic stationary phase in electrochromatography and capiUary liquid chromatography for the enantiomeric separation of hydroxy acids, J. Chromatogr. A, 990, 143, 2003. 

Beesley, T.E., Lee, J.T., and Wang, A.X., Method development and optimization of enantiomeric separations using macrocyclic glycopeptide chiral stationary phases, in Chiral Separation Techniques, Second completely revised and updated edition, Subramanian, G., Ed., Wiley-VCH Weinheim, 2001, 25. 

Xiao, T.L., Reversal of enantiomeric elution order on macrocyclic glycopeptide chiral stationary phases, J. Liq. Chrom. Rel. TechnoL, 24, 2673, 2001. 

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. 

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). 

Table 5 LSER solute descriptors of five molecular enantiomeric pairs and the corresponding Eq. (6) enantioselectivity coefficients obtained on the teicoplanin macrocycUc glycopeptide chiral stationary phase... 

Han X, Huang Q, Ding J, Larock RC, Armstrong DW (2005) Enantiomeric separation of fused polycycles by HPLC with cyclodextrin and macrocyclic glycopeptides chiral stationary phases. Sep Sci Tech 40 2745-2759... 

Abstract The macrocyclic glycopeptide chiral selectors are natural molecules produced by bacterial fermentation. Purified and bonded to silica particles, they make very useful chiral stationary phases (CSP) with a broad spectrum of applicability in enantiomeric separation. The macrocyclic glycopeptide CSPs are multimodal, the same column being able to work in normal phase mode with apolar mobile phase, in reversed-phase mode, or in polar ionic mode with 100% alcoholic mobile phase... 

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... 

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