Chloramphenicol structure

Chirality center, 292 detection of, 292-293 Eischer projections and, 975-978 R,S configuration of, 297-300 Chitin, structure of, 1002 Chloral hydrate, structure of, 707 Chloramphenicol, structure of, 304 Chlorine, reaction with alkanes, 91-92,335-338 reaction with alkenes, 215-218 reaction with alkynes, 262-263 reaction with aromatic compounds, 550 Chloro group, directing effect of, 567-568... 

Hansch, C., Kutter, E. and Leo, A. (1969). Homolytic Constants in the Correlation of Chloramphenicol Structure with Activity. J.Med.Chem., 12,746-749. 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

The major mechanism of resistance to chloramphenicol is mediated by the chloramphenicol acetyltransferases (CAT enzymes) which transfer one or two acetyl groups to one molecule of chloramphenicol. While the CAT enzymes share a common mechanism, different molecular classes can be discriminated. The corresponding genes are frequently located on integron-like structures and are widely distributed among Gramnegative and - positive bacteria. 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

A famous example of the use of nitro compounds in synthesis was the original synthesis of the antibiotic chloramphenicol (8), which is still used to treat tropical diseases. This synthesis also confirmed the structure of chloramphenicol and established that the (-)-thrco compound was the biologically active stereoisomer. 

Antibiotics may be classified by chemical structure. Erythromycin, chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride are antibiotics whose primary structures differ from each other (Fig. 19). Figure 20 shows potential oscillation across the octanol membrane in the presence of erythromycin at various concentrations [23]. Due to the low solubility of antibiotics in water, 1% ethanol was added to phase wl in all cases. Antibiotics were noted to shift iiB,sDS lo more positive values. Other potentials were virtually unaffected by the antibiotics. On oscillatory and induction periods, there were antibiotic effects but reproducibility was poor. Detailed study was then made of iiB,sDS- Figure 21 (a)-(d) shows potential oscillation in the presence of chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride [21,23]. Fb.sds differed according to the antibiotic in phase wl and shifted to more positive values with concentration. No clear relationship between activity and oscillation mode due to complexity of the antibacterium mechanism could be discovered but at least it was shown possible to recognize or determine antibiotics based on potential oscillation measurement. 

FIG. 19 Chemical structures of (a) erythromycin, (b) chloramphenicol, (c) ampicillin, (d) cefpo-doxime proxetil, and (e) doxycycline hydrochloride. 

Fig. 1 Chemical structures of some of the most important antibiotics used nowadays divided into the most representative families fluoroquinolones, sulfonamides, penicillins, macrolides, and tetracyclines. Another important antibiotic, chloramphenicol, is also shown...

It is interesting to note that this method was used in an early analysis of the antibiotic compound chloramphenicol, whose structure includes a nitroaromatic group [30]. 

Figure 1.17. Chemical structure of chloramphenicol, the first broad-spectrum antibiotic to gain clinical...

Figure 9.3 Targets for antibacterial drugs. The various classes of antibacterial drugs exert their effects at one of the four fundamental structural components of bacteria. Each of these components is vulnerable to drug attack. Penicillin, for example, attacks at the level of the cell wall chloramphenicol, however, works at the level of bacterial protein synthesis.

Chloramphenicol (9.82) is a product of a Streptomyces species. Its structure is remarkably simple, and it is obtained synthetically rather than by fermentation. It is a broad-spectrum... 

Crystalline chloramphenicol is a neutral, stable compound with the following structure ... 

Chloramphenicol, thiamphenicol, and florfenicol are broad-spectrum antibacterials with closely related chemical structures (Fig. 3.2). In thiamphenicol, the p-nitro group on the benzene ring of chloramphenicol is replaced with a methyl sulfonyl group. In florfenicol, the hydroxyl group on the side chain of thiamphenicol is replaced with a fluorine. They are all potent antibacterial agents acting... 

Thiamphenicol is a synthetic chloramphenicol analogue with a molecular structure that appears to preserve tlie antibacterial properties, decrease markedly the metabolism by the liver, enhance kidney excretion, and eliminate tlie occurrence of aplastic anemia, although it is probably more liable to cause dose-dependent reversible depression of the bone marrow (15). These properties make it preferable in certain cases to chloramphenicol (36, 37). 

Despite the fact that the preparation of chloramphenicol-specific antibodies was reported as early as in 1966 (36), it was 1984 before the first immunoassay was published for the determination of chloramphenicol residues in swine muscle, eggs, and milk (37). This first-published method was a radioimmunoassay that required an extraction procedure and special laboratory facilities to attain a quantification limit of 1 ppb. Employed polyclonal antibodies showed insignificant crossreactivity with structurally related compounds, except that thiamphenicol that did not interfere with the analysis. However, cross-reactivity was significant for metabolites deviating from the parent compound in the acyl side chain. 

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression. The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol. This rare (1 in 10,000-45.000) chloramphenicol toxicity has been linked to the nitroaromatic function. Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency and has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related structures. 

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