Anticoccidial antibiotics

The kinetic resolution reaction can be used for the asymmetric synthesis of chiral secondary allylic alcohols or their corresponding epoxides. The yield of either is, of course, limited to 50%, starting from the racemic allylic alcohol, but the methodology has found widespread use in organic synthesis. For example, epoxidation of the racemic allylic alcohol 54 gave the epoxide 55, used to prepare the anticoccidial antibiotic diolmycin A1 (5.63). ... 

Tabata N, Tomoda H, Matsuzaki K, Omura S (1993) Stmcture and Biosynthesis of Xanthoquinodins, Anticoccidial Antibiotics. J Am Chem Soc 115 8558... 

Polyethers. Antibiotics within this family contain a number of cycHc ether and ketal units and have a carboxyHc acid group. They form complexes with mono- and divalent cations that ate soluble ia aoapolar organic solvents. They iateract with bacterial cell membranes and allow cations to pass through the membranes causiag cell death. Because of this property they have been classified as ionophores. Monensia, lasalocid, and maduramicia are examples of polyethers that are used commercially as anticoccidial agents ia poultry and as growth promotants ia mmiaants. 

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). 

The polyether antibiotics were first recognized as a separate class with the pubHcation of the structure of monensia ia 1967 (1). Several members of the group have siace found commercial appHcation as anticoccidials ia poultry farming and ia improvement of feed efficiency for mmiaants (see Feeds and FEED additives). 

The polyether antibiotics exhibit a broad range of biological, antibacterial, antifungal, antiviral, anticoccidial, antiparasitic, and insecticidal activities. They improve feed efficiency and growth performance in mminant and monogastric animals. Only the anticoccidial activity in poultry and catde, and the effect on feed efficiency in mminants such as catde and sheep are of commercial interest. 

Table 3 Hsts the polyether antibiotics used as poultry anticoccidial dmgs in the United States. Recendy, lasalocid and monensin have been approved for use in bovine coccidiosis at levels in feed of 11—33 g/t.

Anticoccidial activity, of polyether antibiotics, 20 135-136 Anticoccidials, 20 135—136 Anticorrosion agents, molybdenum compounds in, 17 39 Anticorrosion coatings, organic titanium compounds in, 25 134 Anti-corrosion metallic coatings, 1 713-714 Anticorrosion pigments, 19 411 Antidegradants... 

Some of these newer products are already taking an increasing share of the market. The discovery of the anticoccidial activity of monensin opened an entirely new field for the use of antibiotics in agriculture. 

Among the anticoccidials, polyether antibiotics constitute the most widely used agents by the poultry industry over the last two decades. They provide excellent disease control and are refractory to development of resistance (15). 

Senidui-amicin is a relatively new polyether antibiotic that exhibits potent antimicrobial and anticoccidial activities. It is intended for use in broilers at a dosage of 25 ppm in the feed for 7 consecutive days. 

At present, liquid chromatography has become the most widely used technique for determining anticoccidial drugs in edible animal products (Table 29.11). The separation of these drugs is generally done on nonpolar reversed-phase columns (octadecyl, octyl and phenyl), the preferred type being the octadecyl bonded silica. However, polar (389, 390, 392, 398, 400) columns have also been used for the determination of the polyether antibiotics in edible animal products. 

Anticoccidial agents -polyether antibiotics as [ANTIBIOTICS - POLYETHERS] (Vol 3)... 

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). 

H-pyran synthesis from, 3, 739 tautomerism, 3, 644 UV spectra, 3, 598 Ionophore A23187 as antibiotic, 4, 374 Ionophore X14547A as antibiotic, 4, 374 Ionophores, 7, 732, 755 anticoccidial activity veterinary use, 1, 213... 

Figure 2 Examples of polyketides. Polyketides demonstrate a broad range of biological activities, including antibiotic (oxytetracycline and erythromycin), antitumor (doxorubicin and dynemicin), antiparasitic (avermectin), and immunosuppressive (FK506). Monensin is used as a bovine feed supplement and an anticoccidial agent.

Further antibiotics, mainly derived from actinomycetes, are used for special applications in human and veterinary medicine [20]. These compounds have numerous chemical structures. The macrolides, tetracyclines, aminoglycosides, glycopeptides, and ansamycins for instance are used in antibacterial treatment whereas the anthracyclines reached the market to supplement anticancer chemotherapy. The fairly toxic polyether-type antibiotics are preferably used as anticoccidial agents. Due to the dramatically increasing resistance of clinical important bacterial strains new targets for the discovery of novel types of antibacterial agents are urgently needed. 

Previous Literature. As the importance of resistance has become apparent, a steadily increasing amount of research has been done to understand and combat it. Excellent summaries of earlier work, with extensive references to the original literature, are available in recent books and review articles, some dealing with all areas of agrochemistry (5-4), and others addressing specific classes of pests (insects, 9-11 fungi, 12,14 weeds, 14). Information on resistance to rodenticides, antibiotics, and anticoccidial drugs, which are not covered in this volume, is available in two of the references (2/5). 

Among anticoccidials, polyether antibiotics have been the most widely used in the broiler industry over the last two decades because they provide excellent disease control and are refractory to resistance development (3). Polyether antibiotics are branch chained, polyoxygenated carboxylic acids that act as mobile carriers of cations (4) by rendering cations lipid-soluble, thereby enabling them to pass across membranes. This process disrupts cationic cross-membrane gradients and is responsible for their anticoccidial activity T3J. 

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