Monovalent Polyether Antibiotics

Monensin was the first polyether antibiotic to have its structure solved by crystallographic methods. In the silver salt, the monensin anion is wrapped around the 

Recently, crystal structures of three different monensin complexes with sodium have been published One of these is a NaBr complex in which the carboxy 

Evidence is added to this viewpoint by inspection of the structures of the grisorixin complexes with Ag and Tl (ionic radii 1.26 and 1.47 A, resp.) as revealed by X-ray analysis The cavity containing the cation is slightly dilated in the 

Spectroscopic studies including H-, C-, Na-, Li-, and ° T1-NMR 07.124-127) have provided conformational assignments for monensin and its ion complexes in 

Monensin appears to be a good example to demonstrate how a biological host molecule utilizes a number of minor conformational changes in order to rearrange its binding sites for optimum complex formation with a guest entity. 

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The structural features described for monensin have been found in all the monovalent polyether antibiotic complexes studied. In some instances, e.g. nigericin568 and dianemycin,569... 

Table 7a. Coordination and hydrogen bonding in metal ion complexes of monovalent polyether antibiotics... 

The divalent polyether antibiotics have revealed the existence of dimeric molecules as monomeric complexes in their interaction with alkali and alkaline earth cations. Lasolocid (145) forms complexes of the type M+L and these may be monomeric when formed and recovered from methanol, but dimeric when recrystallized from the non-polar carbon tetrachloride. The shortened ligand backbone relative to the monovalent polyethers does not allow complete shielding of the cation from the solvent, and so in non-polar solvents this is overcome by dimerization. If the salicylate and tetrahydropyran moieties present in (145) are referred to as the head and the tail of the molecule then two forms of dimerization may be envisaged head-to-tail and head-to-head . 

S. malachitofuscus produces X14766A, the only chlorine containing polyether antibiotic (39) described so far. The producer was isolated from the Mexican soil in 1976. The antibiotic is active against Gram-positive bacteria forming strong complexes with both monovalent and divalent metals (K, Na, Rb, Cs, Ba, Sr, Ca, Mg, Li) [27,28]. 

Mr 724.97, mp. 183.5-185 °C. A polyether antibiotic from cultures of Streptomyces hygro-scopicus and other streptomycetes. N. acts as an ion-ophore for monovalent cations in mitochondria, is active against Gram-positive bacteria and is used as a coccidiostatic agent... 

C42H70O11, Mr 751.01, cryst., mp. 112.5-113.5 °C, [a]o -63 (C2H5OH), an ionophoric polyether antibiotic with a dispiroketal structure produced by Strep-tomyces albus it preferentially forms complexes with monovalent cations (Na ). S. is formed biosyntheti-cally on the polyketide pathway, cyclization in the linear carboxylic acid proceeds on the diene/diepox-ide pathway. The 20-deoxy derivative is also formed. S. is used against coccidiosis in poultry breeding and also has antiviral activity (HIV). LD50 (mouse p.o.) 50 mg/kg. 

Polyether antibiotic. See also Antibiotic A 130B, A-736 and Antibiotic A 130C. Isol. from Streptomyces hygroscopicus. Monovalent ionophore showing antimicrobial activity. Growth promotor. Amorph. powder. [a]o -t-64.5 (c, 1 in CHCI3). Related to Dianemycin. Tmax 235 ( 14000) (EtOH) (Derep). 

Ionophores, or polyether (PET) antibiotics, produced by various species of Streptomyces, possess broad spectrum anticoccidial activities. They are chemically characterized by several cyclic esters, a single terminal carboxylic acid group, and several hydroxyl groups. Representative members of this class include salinomycin (SAL), monensin (MON), lasalocid (LAS), narasin (NAR), maduramicin (MAD), and semduramicin (SEM). The main chemical properties of interest in the extraction methodology are their low polarities and instability under acidic conditions. They are able to form stable complexes with alkaline cations. All of these compounds, with the exception of LAS, bind monovalent cations (e.g., Na+ and K+). Lasalocid has a tendency to form dimers and can form complexes with divalent cations such as Mg2+ and Ca2+. The formation of metal complexes results in all of these compounds adopting a quasi-cyclic formation consequent to head-to-tail hydrogen bonding. No MRLs have yet been set by the EU for any of the carboxylic acid PETs (98). 

Considerable work has been directed to the search for better neutral carriers, motivated by the very successful valinomycin sensor for potassium (23-2II). Impetus was given to the development of this electrode by the observation of Moore and Pressman (102) that the antibiotic is capable of actively transporting potassium across rat mitochondria membranes. There are numerous synthetic macrocyclic polyethers capable of forming complexes with monovalent cations. Some of the earliest ISE studies were by Rechnitz and Eyal (103) on dicyclohexyl- and dibenzo-l8-crown-6 ligands synthesized by Pedersen (104). Soon... 

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