Macrocyclic antibiotics, literature

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. 

Impetus was given to work in the field of selective cation complex-ation by the observation of Moore and Pressman (5) in 1964 that the macrocyclic antibiotic valinomycin is capable of actively transporting K+ across mitochondrial membranes. This observation has been confirmed and extended to numerous macrocyclic compounds. There is now an extensive literature on the selective complexation and transport of alkali metal ions by various macrocyclic compounds (e.g., valinomycin, mo-nactin, etc.) (2). From solution spectral (6) and crystal X-ray (7) studies we know that in these complexes the alkali metal cation is situated in the center of the inwardly oriented oxygen donor atoms. Similar results are found from X-ray studies of cyclic polyether complexes of alkali metal ions (8) and barium ion (9). These metal macrocyclic compound systems are especially noteworthy since they involve some of the few cases where alkali metal ions participate in complex ion formation in aqueous solution. 

One significant commercial development which has been taking place is that it has been demonstrated that macrocyclic antibiotic CSP may be used successfully with normal phase solvents, mixtures of n-hexane and ethanol being the most frequently used. Most of the illustrative examples cited in the commercial literature feature non-polar analytes not all of which are of pharmaceutical interest (Fig. 3.6) but nonetheless it is a good selling point that these CSP may be used with the complete range of mobile phase polarities. 

Researches regarding the separation of dansyl-DL-amino acids by normal-phase TLC on plates impregnated with a macrocyclic antibiotic [73] and amino acids from small peptides on reversed-phase TLC [74] are given in literature. 

A number of polyoxygenated fungal metabolites are assembled from C2, C3, and C4 units. Starter units of propionyl-CoA and successive additions of methylmalonyl-CoA are especially important in the formation of many of these compounds (O Hagan, 1990). Most of these metabolites possess large rings and are potent antibiotics they are known collectively as macrocyclic or macrolide antibiotics. One well-known example of this group of compounds is erythromycin A (34) from Streptomyces erythreus (Fig. 5.18) (Omura, 1984 Simpson, 1984). An extensive literature deals with these antibiotic compounds but is beyond the scope of this text. 

Examples of the use of these chiral building blocks in the synthesis of drugs and natural products abound in the literature. They include the synthesis of grahamimycin the macrocyclic component of the antibiotic elaiophylin, fungicides norpyrenophorin, pyrenophorin and vermiculin, phorcantholide I and J, which are defensive secretions of the eucarypt longicorn beetle,citronellol and a pheromone of the western corn rootworm. Clearly the monomeric chiral derivatives of PHB have a role to play in enantiomer-specific synthesis. 

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