Macrocyclic glycopeptides applications

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. 

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. 

Because of their diverse functionality, it is not surprising to see that CSPs based on macrocyclic glycopeptides, i.e., Chirobiotic phases, have a broad-spectrum applicability in all HPLC conditions, namely normal-phase, reversed-phase, polar organic,... 

In recent years, the application of macrocyclic glycopeptide CSPs has been expanded to SFC, and teicoplanin aglycone phase (Chirobiotic TAG) was found to be the most effective closely followed by teicoplanin CSP (Chirobiotic T) [144, 184]. Because of a large number of polar groups available on the Chirobiotic CSPs, it is often required to work with considerable amount of polar additives in the mobile... 

Chiral Recognition with Macrocyclic Glycopeptides Mechanisms and Applications... 

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... 

Since the natural target of macrocyclic antibiotics is the A-acyl-D-alanyl-D-alanine terminus (see Section 2.1), the early choice of suitable substrates for this kind of CSPs was that of amino acids [45]. However, it turned out that the macrocyclic CSPs were very successful not only in amino acids enantioresolution, but also in the separation of a wide variety of different structures. The early stages of application of macrocyclic antibiotics have been surveyed in the different fields of chromatography [1,2]. A summary of the different categories of chiral compounds separated by HPLC on glycopeptides containing CSPs is reported in Table 2.3. 

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]. 

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. 

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