Macrocyclic antibiotics chiral recognition mechanism

Different classifications for the chiral CSPs have been described. They are based on the chemical structure of the chiral selectors and on the chiral recognition mechanism involved. In this chapter we will use a classification based mainly on the chemical structure of the selectors. The selectors are classified in three groups (i) CSPs with low-molecular-weight selectors, such as Pirkle type CSPs, ionic and ligand exchange CSPs, (ii) CSPs with macrocyclic selectors, such as CDs, crown-ethers and macrocyclic antibiotics, and (iii) CSPs with macromolecular selectors, such as polysaccharides, synthetic polymers, molecular imprinted polymers and proteins. These different types of CSPs, frequently used for the analysis of chiral pharmaceuticals, are discussed in more detail later. 

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. 

HPLC Chiral Stationary Phases Containing Macrocyclic Antibiotics Practical Aspects and Recognition Mechanism... 

Commercially available silica gel plates coated with acid or basic chiral selectors [o-galacturonic acid, l-(- -)-tartaric acid, L-lactic acid, (-)-brucine] were used for the separation of racemic ephedrine, atropine, neutral amino acids, and their 3-phenyl-2-thiohydantoins (PTH) derivatives. The use of amino acids as chiral selectors involved further possibilities of enantiomer separation owing to the simultaneous presence of basic and acidic groups. In fact, L-aspartic acid, L-lysine, L-histidine, L-arginine, and L-ser-ine resolved racemic alkaloids, (3-blockers, profens, some amino acids, and their Dns derivatives. Macrocyclic antibiotics [i.e., (-)-erythromycin and (-)-vancomycin] were also used as chiral agents for the separation of enantiomeric DNs amino acids. The mechanisms of chiral recognition was investigated by Aboul-Enein, El-Awady, and Heard they hypothesized that the formation of... 

D Acquarica 1, Gasparrini F, Misiti D, Pierini M, VUlani C (2008) HPLC chiral stationary phases containing macrocyclic antibiotics practical aspects and recognition mechanism. Adv Chromatogr 46 109-174... 

Abstract Medical studies established that vancomycin and other related macro-cyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide stmcturally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin s mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition. 

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