Antibiotics macrocyclic

Chiral stationary phases in tic have been primarily limited to phases based on normal or microcrystalline cellulose (44,45), triacetylceUulose sorbents or siHca-based sorbents that have been chemically modified (46) or physically coated to incorporate chiral selectors such as amino acids (47,48) or macrocyclic antibiotics (49) into the stationary phase. 

Isothiazole substituents have been attached to /3-lactam antibiotics and to macrocyclic antibiotics such as erythromycin. The sulfa drug, Sulfasomizole (244) also has good antibacterial activity. Thiosemicarbazones of 5-formyl- and 5-acetylisothiazoles show high activity against the pox group of viruses (65AHC(4)107). 

This relatively new class of CSPs incorporates glycopeptides attached covalently to silica gel. These CSPs can be used in the normal phase, reversed phase, and polar organic modes in LC [62]. Various functional groups on the macrocyclic antibiotic molecule provide opportunities for tt-tt complexation, hydrogen bonding, and steric interactions between the analyte and the chiral selector. Association of the analyte... 

The macrocyclic antibiotic-based CSPs have not been used extensively in SFC. Two macrocyclic antibiotic CSPs, Chirobiotic T and Chirobiotic V, were included in a study of various CSPs in SFC. At least partial resolution of approximately half of the 44 test compounds could be obtained on these two CSPs in SFC [63]. A high concentration of modifier was necessary to elute some of the analytes. Enantioreso-lution of derivatized amino acids was also demonstrated in the same study. Flowever, a complex modifier comprised of methanol, water, and glycerol was required for separations performed on the Chirobiotic T CSP. The separation of coumachlor enantiomers on a vancomycin-based CSP (Chirobiotic V) in SFC is illustrated in Fig. 12-5 [32]. 

Mixing the additive in the eluent used as a mobile phase can also modify the chromatographic system (dynamic modification), but the use of modified adsorbents has led to an improvement of resolution. Example works include that by Armstrong and Zhou [11], who used a macrocyclic antibiotic as the chiral selector for enantiomeric separations of acids, racemic drugs, and dansyl amino acid on biphenyl-bonded silica. 

Many chiral compounds can be used as selectors, for example, chiral metal complexes, native and modified cyclodextrins, crown ethers, macrocyclic antibiotics, noncyclic oligosaccharides, and polysaccharides all have been shown to be useful for efficient separation of different types of compounds. 

Wide-spectrum antimicrobial /1-lactam antimicrobial Macrocyclic antibiotic Antimicrobial... 

Rifamycin B (136), a macrocyclic antibiotic of the ansamycin class, associates enan-tioselectively with amino alcohols. As 136 bears a carboxyl group, it can be used as a host molecule to resolve enantiomeric mixtures by CE. This was applied to analyze a variety of drugs, including terbutalin (137), bamethan (138), norphenylephrine (139),... 

The PO mode is a specific elution condition in HPLC enantiomer separation, which has received remarkable popularity especially for macrocyclic antibiotics CSPs and cyclodextrin-based CSPs. It is also applicable and often preferred over RP and NP modes for the separation of chiral acids on the cinchonan carbamate-type CSPs. The beneficial characteristics of the PO mode may arise from (i) the offset of nonspecific hydrophobic interactions, (ii) the faster elution speed, (iii) sometimes enhanced enan-tioselectivities, (iv) favorable peak shapes due to improved diffusive mass transfer in the intraparticulate pores, and last but not least, (v) less stress to the column, which may extend the column lifetime. Hence, it is rational to start separation attempts with such elution conditions. Typical eluents are composed of methanol, acetonitrile (ACN), or methanol-acetonitrile mixtures and to account for the ion-exchange retention mechanism the addition of a competitor acid that acts also as counterion (e.g., 0.5-2% glacial acetic acid or 0.1% formic acid) is required. A good choice for initial tests turned out to be a mobile phase being composed of methanol-glacial acetic acid-ammonium acetate (98 2 0.5 v/v/w). 

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

This review provides an overview of the literature published to date on macrocyclic antibiotics exploited for enantioselective separations in high-performance liquid chromatography (HPLC). It was not intended as a comprehensive issue on the applications of such antibiotics in sub- and supercritical fluid chromatography (SFC), thin layer chromatography (TLC), capillary electrophoresis (CE), and capillary electrochromatography (CEC). A number of structural properties of the most important macrocyclic antibiotics applied in HPLC enantioseparations are listed in Table 2.1. 

Structural Properties of the Most Important Macrocyclic Antibiotics Applied in HPLC Enantioseparations... 

Vancomycin was the first macrocyclic antibiotic evaluated as selector for the synthesis of HPLC chiral stationary phases (CSPs) [7], along with rifamycin B (among ansamycins) and thiostrepton (among polypeptides). 

Avoparcin was the fourth macrocyclic antibiotic evaluated as selector for the synthesis of HPLC CSPs [37]. 

Macrocyclic antibiotics also include a family of thiopeptides, of which thiostrepton (Figure 2.11) is the parent compound and the most complex member. Produced by Streptomyces azureus [59], thiostrepton includes 10 rings, 11 peptide bonds, extensive unsaturation, an imine functionality, a secondary amine, and 17 stereogenic centers [60] it also contains five thiazole rings and one quinoline nucleus. 

This strategy consists in the initial modification of the silica surface with organosilanes having suitable anchoring groups, which are either reactive themselves or can be additionally activated for the final attachment of the chiral selector. The choice of the proper silane will depend on the presence of suitable functional groups on the chiral entity to be fixed to the matrix. As macrocyclic antibiotics contain hydroxyl, amine, and carboxylic acid functionalities, they can be linked to the silica surface in a variety of different ways [7, 55]. The obvious drawback of the stepwise assemblage of chiral selectors on the silica surface is the eventual formation of additional polar or ionizable sites on the matrix, which may cause unselective retention of chiral analytes. 

Synthetic Strategies for the Immobilization of Macrocyclic Antibiotics Surface Coverage Data... 

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