Macrolide antibiotics erythromycin

The hydroxy groups in natural products like, for example, the macrolide antibiotics erythromycin, 1"1 and desmycosin, 2001 2011 as well as the 3-(hydroxymethyl)-2- or 3-cephems 2021 and derivatives of the amino sugar garamin 2031 have been converted into the carbamate function with CDI and amines. In the case of aminoglycoside antibiotics of the sisomicin series, thiocarbamates or dithiocarbamates have been prepared from alcohols or thiols using ImCSIm and amines.12041... 

Fig. 4.9 Structures of the macrolide antibiotics, erythromycin (monobasic) and azithromycin (dibasic).

Another example of solid phase DOS involves post-modification of the natural product macrolide antibiotic erythromycin (34) [77]. Erythromycin was first converted to analogue 32 which resembles a third generation macrolide antibiotic with high activity against resistant strains (ABT-773, 35), but is attached to solid phase-bound amino acids by reductive amination. Two further reductive amination steps and cleavage from solid support form a library of compounds of type 33 (Fig. 10). 

A4 inhibitors - Patients receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole, and miconazole), or cyclosporine or vinblastine should not receive doses of tolterodine greater than 1 mg twice/day (greater than 2 mg/day for ER capsules). 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

In his 1956 article in Perspectives in Organic Chemistry , the late Professor R. B. Woodward characterized the macrolide antibiotic erythromycin as a synthetic challenge which is ... quite hopelessly complex, especially in view of its plethora of asymmetric centers 70). Twenty-five years after making this dismal prognosis,... 

The risk of myopathy appears to be increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Lovastatin is metabolized by the CYP isoform 3A4. Certain drugs, that share this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include cyclosporine, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, HIV protease inhibitors, the antidepressant nefazodone, or large quantities of grapefruit juice (greater than 1 quart daily)... 

The macrolide antibiotic erythromycin together with statins enhances the risk of rhabdomyolysis (SED-13, 1328) (112), as do clarithromycin and azithromycin (113). 

A major aim of enteric coating is protection of drugs that are sensitive or unstable at acidic pH. This is particularly important for drugs such as enzymes and proteins, because these macromolecules are rapidly hydrolyzed and inactivated in acidic medium. Antibiotics, especially macrolide antibiotics like erythromycin, are also rapidly degraded by gastric juices. Others, such as acidic drugs like NSAID s (e.g., diclofenac, valproic acid, or acetylsalicylic acid) need to be enteric coated to prevent local irritation of the stomach mucosa. 

Honig PK, Wortham DC, Zamani K, et al. Comparison of the effect of macrolide antibiotics erythromycin, clarithromycin and azithromycin on terfenadine steady-state pharmacokinetics and electrocardiographic parameters. Drug Invest 1994 7 148-156. 

An asymmetric aldolization was successfully applied to the preparation of gibbane. The total synthesis of the macrolide antibiotic erythromycin was developed involving an asymmetric aldolization step catalyzed by proline. Since the mid-1970s, a flood of papers has appeared dealing with the asymmetric aldolization of various triketones. Some results are listed for comparison in Table 1. 

Macrolide Antibiotics. Erythromycin may significantly increase serum concentrations of medications such as theophylline by inhibiting their hepatic metabolism. Clarithromycin (Biaxin) and troleandomycin appear to interact with other medications in a manner similar to erythromycin, whereas azithromycin (Zithromax) is unlikely to interact with these agents. 

Macrolide antibiotics are glycosides with a macrocyclic lactone aglycon, which is formed in the polyketide biosynthetic pathway [38,39]. The lactone ring is 12-, 14-, 16-, or 18-mem-bered. The polyoxo-macrolides such as the classical antibiotic erythromycin are produced by streptomyces microorganisms and form a clinically important group of polyketide antibiotics. Erythromycin (O Fig. 5) is the major component out of a mixture of macrolide antibiotics which is formed by Saccharopolyspora erythraea. It contains two deoxysugars attached to the aglycon, L-cladinose and D-desosamine. 

A quantitative bioassay for erythromycin 2 -ethylsuccinate (EM-ES, M, 861 Da), a prodrug of the macrolide antibiotic erythromycin, using Cf-FAB LC-MS was described by Kokkonen et al. [53-54]. Reversed-phase LC of extracted plasma samples was performed at a flow-rate of 1 ml/min. In order to meet the flow-rate requirements of the Cf-FAB interface, i.e., 15 pl/min, without splitting, the phase-system switching approach [53] was used. After post-column dilution of the column effluent with water, the eluent fraction of interest was enriched on a short precolumn, from which the compound of interest was desoibed and transferred to the Cf-FAB interface probe. A [ Hj]-analogue was used as internal standard. Good linearity was observed in the range of 0.1 to 10 pg/ml EM-ES in plasma. The within-ran precision was ca. 6%. The accuracy and inter-day precision, determined at 1.05 pg/ml in plasma, were 0.93 0.11 pg/ml and 12%, respectively (n=6). The determination limit was 0.1 pg/ml [54]. 

The performance of HSCCC-ESI-MS was evaluated by analyzing erythromycins and didemnins [10]. Because erythromycins (macrolide antibiotics) show weak UV absorbance and cannot be detected easily with a conventional UV detector, mass spectrometric detection is a very useful technique for analysis of these antibiotics. A mixture of erythromycin A (Er-A,... 

The macrolide antibiotics (erythromycin, azithromycin, and chn-damycin) exhibit anti-inflammatory properties in patients with acne. 

Erythromycin was discovered in 1952 in the metabolic products of a strain of Streptomyces erythreus. Clarithromycin and azithromycin are semisynthetic derivatives of erythromycin. Macrolide antibiotics contain a many-membered lactone ring (14-membered rings for erythromycin and clarithromycin, and a 15-membered ring for azithromycin) to which are attached one or more deoxy sugars. Clarithromycin differs from erythromycin only by methylation of the hydroxyl group at the 6 position, and azithromycin differs by the addition of a methyl-substituted... 

Raghoebar, M., Lindeyer, E., Van den Berg, W. B., and Van Ginneken, C. A. M. (1988). On the mechanisms of association of the macrolide antibiotic erythromycin with isolated human polymorphonuclear leucocytes. Biochem. Pharmacol. 38, 3221-3227. 

It is widely accepted that MLS antibiotics inhibit protein synthesis by binding to closely related sites on the 508 subunit of the 70S ribosome of bacteria [4], despite being structurally different from each other (see Figs. 1 and 2 in a later section). That is the reason why, when inducible resistant Staphylococcus aureus cells are exposed to a low concentration of the drug (0.05 tg erythromycin/ml - 6.8 x 10 M), they show resistance against not only erythromycin but also other macrolide antibiotics as well as lincosamide and type B streptogramin antibiotics. Erythromycin has been widely used and has been the object of extensive molecular and biological studies. 

Yazawa, K., Mikami, Y, Sakamoto, T., Ueno, Y., Morisaki, N., Iwasaki, S., and Furihata, K. (1994). Inactivation of the macrolide antibiotics erythromycin, midecamycin, and rokitamycin by pathogenic Nocardia species. Antimicrob. Agents Chemothen 38, 2197—2199. 

In 1952 the broad-spectrum antibiotic erythromycin was isolated from cultures of Streptomyces erythreus (later renamed Saccharopolyspora erythraed). The erythromycins are macrolide antibiotics that typically have a 12-, 14-, or 16-membered cycHc backbone which is a lactone (a cychc ester see Figure 4). 

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