Antibiotics, reviews

All of the older antibiotics reviewed in this chapter are bacteriostatic inhibitors of protein synthesis acting at the ribosomal level (Figure 44-2). The binding sites for chloramphenicol, macrolides, and... 

Aminoglycoside and Aminocyclitol Antibiotics Reviews have appeared on new semi-synthetic aminoglycoside antibiotics, with particular reference to habekacin and polydeoxy-... 

Chloroacetoacetic esters are important industrial intermediates used especially for the synthesis of the aniinothia2olylacetic acid side chain of modem cephalosporins (see Antibiotics, P-LACTAMS-cephalosporins). For a review of the chemistry of 4-chloroacetoacetates see Reference 112. 

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

The presence of many nonprotein amino acids has been reported in various living metaboUtes, such as in antibiotics, some other microbial products, and in nonproteinaceous substances of animals and plants (7). Plant amino acids (8) and seleno amino acids (9) have been reviewed. 

Occurrence, Fermentation, and Biosynthesis. Although a large number of Streptomjces species have been shown to produce carbapenems, only S. cattkja (2) and S. penemfaciens (11) have been reported to give thienamycin (2). Generally the antibiotics occur as a mixture of analogues or isomers and are often co-produced with penicillin N and cephamycin C. Yields are low compared to other P-lactams produced by streptomycetes, and titres are of the order of 1—20 p-g sohdusmL despite, in many cases, a great deal of effort on the optimization of the media and fermentation conditions. The rather poor stabiUty of the compounds also contributes to a low recovery in the isolation procedures. The fermentation and isolation processes for thienamycin and the olivanic acids has been reviewed in some detail (12). 

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). 

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid iacorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted iadole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteiae (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used ia the United States only as a poly antimicrobial vetetinary ointment (Panalog, Squibb), but thiazole antibiotics have, ia the past, been used as feed additives ia various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

Because of the complexity of the polyether antibiotics tittle progress has been made in stmcture determination by the chemical degradation route. X-ray methods were the techniques most successfully applied for the early stmcture elucidations. Monensin, X206, lasalocid, lysocellin, and salinomycin were included in nineteen distinct polyether x-ray analyses reported in 1983 (190). Use of mass spectrometry (191), and H (192) and nmr (141) are also reviewed. More recently, innovative developments in these latter techniques have resulted in increased applications for stmcture determinations. Eor example, heteronuclear multiple bond connectivity (hmbc) and homonuclear Hartmann-Hahn spectroscopy were used to solve the stmcture of portimicin (14) (193). East atom bombardment mass spectrometry was used in solving the stmctures of maduramicin alpha and co-factors (58). 

The most thoroughly studied mode of /3-lactam hydrolysis is that catalyzed by the enzyme /3-lactamase (EC 3.5.2.6). The elaboration of this enzyme is one of the three principal ways in which a bacterium can obtain resistance to a /3-lactam antibiotic (see Section 5.11.5.1), and much of the chemical work carried out on the penicillin molecule has been related to attempts to deal with this problem. A discussion of the /3-lactamases is beyond the scope of this work. The reader is referred to (B-79MI51101) for a recent review. 

The mechanism of action of -lactam antibiotics has been the subject of several recent reviews <79MI51102, 79MI51103, 81MI51104, B-81MI51105, B-82MI51101). 

Lactam antibiotics, 1, 152-153 applications, 7, 353 mechanism of action, 7, 338 nuclear analogues, 7, 354 synthesis, 7, 351, 353 in synthesis reviews, 1, 67 -Laetamase effeet... 

Chem. Pharm. Bull., Japan Chem. Soc. Review Helv. Chim. Acta Heterocycles J. Antibiotics J. Am. Chem. Soc. 

Since Pressman s early observation that antibiotics of the nigericin type complexed cations there has been considerable effort expended to mimic this action using simple, readily synthesized molecules. Simon and his collaborators have been especially active in this approach and have reviewed this area . They have devised a number of struc-... 

For reviews of synthetic achievements in the polyether field, see (a) Kishi, Y. In Polyether Antibiotics Naturally Occurring Acid lonophores, Westley,... 

This series in heterocychc chemistry is being introduced to collectively make available critically and comprehensively reviewed hterature scattered in various journals as papers and review articles. All sorts of heterocyclic compounds originating from synthesis, natural products, marine products, insects, etc. will be covered. Several heterocyclic compounds play a significant role in maintaining life. Blood constituents hemoglobin and purines, as well as pyrimidines, are constituents of nucleic acid (DNA and RNA). Several amino acids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocyclic compounds that are essential for life. Heterocyclic compounds are widely used in clinical practice as drugs, but all applications of heterocyclic medicines can not be discussed in detail. In addition to such applications, heterocyclic compounds also find several applications in the plastics industry, in photography as sensitizers and developers, and the in dye industry as dyes, etc. 

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