Polyether ionophore

The FDA first approved use of a polyether ionophore as a feed additive for catde ia 1975. Ionophores were first isolated from bacteria generally of the Streptomjces genus, but are produced commercially by bacterial fermentation (qv). Monensia [17090-79-8] and other ionophores are being fed to over 90% of feedlot cattle grown for beef (53) to enhance efficiency of gain improvements of 5—10% are common. Ionophores also are used as anticoccidial dmgs ia poultry production and have similar, but lesser, effects ia mminants (54). 

Coccidiosis is a proto2oal disease of the intestinal tract of animals that leads to severe loss of productivity and death. The development and widespread use of anticoccidials has revolutionized the poultry industry. The estimated world market for anticoccidial agents in 1989 was 425 million and this was dominated by the polyether ionophore antibiotics monensin, salinomycin [53003-10-4], n imsm [55134-13-9], la.s9locid, and maduramicin [84878-61-5] (26). 

Anticoccidial Activity. The 1968 report that claimed monensin has activity against Eimeria sp., particularly E. tenella E. macdma., and E. acervulina greatly altered the prevention and control of coccidiosis in poultry (172). It is estimated that the polyether ionophores presently constitute more than 80% of the total worldwide usage of anticoccidials (173). Lasalocid and monensin have been approved for use in control of coccidiosis in cattle. 

Chemical modification of monensin, polyether ionophoric antibiotic with bound tetrahydropyran, two tetrahydrofuran, and octahydrospiro-2,2 -furopyran fragments 97YZ583. 

Crown ethers are molecular hosts that are also polyether ionophores. 

Calcium-selective electrodes have long been in use for the estimation of calcium concentrations - early applications included their use in complexometric titrations, especially of calcium in the presence of magnesium (42). Subsequently they have found use in a variety of systems, particularly for determining stability constants. Examples include determinations for ligands such as chloride, nitrate, acetate, and malonate (mal) (43), several diazacrown ethers (44,45), and methyl aldofuranosides (46). Other applications have included the estimation of Ca2+ levels in blood plasma (47) and in human hair (where the results compared satisfactorily with those from neutron activation analysis) (48). Ion-selective electrodes based on carboxylic polyether ionophores are mentioned in Section IV.B below. Though calcium-selective electrodes are convenient they are not particularly sensitive, and have slow response times. 

Monensin belongs to the family of polyether ionophores. These compounds consist of a series of tetrahydrofuran and tetrahydro-pyran rings and have a carboxyl group that forms neutral salts with alkali metal cations. Their three-dimensional structure presents a lipophilic hydrocarbon exterior with the cation encircled in the oxygen-rich interior. They probably act by transporting cations through the lipid bi-layer of cell membranes, thereby preventing the concentration of potassium by the cells. Evidence for this is... 

Awkward Anticoccidial drugs are extensively used in the poultry industry to control infection. The polyether ionophores, such as narasin and salinomycin, are the most commonly used coccidiostats in poultry. 

Fig. 5.4 Chemical structures of commonly used polyether ionophore antibiotics.

CT Elliott, DG Kennedy, WJ McCaughey. Methods for the detection of polyether ionophore residues in poultry. Analyst 123 45R-56R, 1998. 

A polymeric stack of macrocycles has been synthesized [6.72] and a cyclodextrin-based model of a half-channel has been reported [6.73]. Channel-type conduction of Na+ ions has been reported for a tris-macrocyclic ligand [6.74]. A derivative of the acyclic polyether ionophore monensin forms lithium channels in vesicles [6.75a], which may be sealed by diammonium salts [6.75b]. 

Dutton CJ, Banks BJ and Cooper CB (1995) Polyether ionophores. Nat Prod Rep 12, 165-181. 

Robinson JA (1991) Chemical and biochemical aspects of polyether-ionophore antibiotic biosynthesis. Prog Chem Org Nat Prod 58, 1-81. 

As with the TMS ethers discussed in the previous section, TES ethers are subject to widely variable rates of cleavage depending on the steric and electronic environment, For example, in a synthesis of the polyether ionophore antibiotic Salinomycin, a primary TES ether was cleaved in preference to a tertiary TES ether by using HF pyridine complex at room temperature [Scheme 4.18].21... 

Selected examples of other biocatalytic asymmetric oxidations are shown in Figure 20.10. In the area of the polyether ionophore monensin a recently proposed mechanism of oxidative cycUzation of a linear polyketide intermediate by four enzymes, the products of monBI, monBll, monCI, and monCII, has been supported experimentally by analysis of a biosynthetic gene cluster [110] and the accumulation of an B,F,F-triene, when oxidative cydization was blocked [111]. 

Monensins A 2 and B 3 are polyether ionophores produced by Streptomyces cinnamonensis that differ only in the sidechain... 

J, Leadlay PF, Spencer JB. Evidence that a novel thioesterase is responsible for polyketide chain release during biosynthesis of the polyether ionophore monensin. ChemBioChem 2006 7 1435— 1442. 

D.A. Volmer, C.M. Lock, ESI and CID of antibiotic polyether ionophores. Rapid Commun. Mass Spectrom., 12 (1998) 157. 

Penicillin, the first natural antibiotic produced by genus Penicillium, discovered in 1928 by Fleming, as well as sulfonamides, the first chemotherapeutic agents discovered in the 1930s, lead a long list of currently known antibiotics. Besides 3-lactams (penicillins and cephalosporines) and sulfonamides, the list includes aminoglycosides, macrolides, tetracyclines, quinolones, peptides, polyether ionophores, ri-famycins, linkosamides, coumarins, nitrofurans, nitro heterocytes, chloramphenicol, and others. 

Schneider, R.P. Lynch, M.J. Ericson, J.F. Fouda, H.G. Electrospray ionization mass-spectrometry of semdurami-cin and other polyether ionophores. Anal. Chem. 1991, 63, 1789-1794. 

Toxoplasmosis - Using Toxoplasma gondii in cell culture, the polyether ionophores lasalocid and monensin were highly active whereas ormetoprim and sulfadimethoxime or a combination were inactive or weakly active. 

---