Macrolide antibiotics, 16-membered erythromycin derivatives

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... 

Cladinose analogues of 16-membered macrolide antibiotics have been prepared. Ethyl P-L-cladinoside was produced by ethanolysis of erythromycin A, and, after alkylation at 0-4, the alkylated products were linked to 0-4 of the mycaminose residue to give 3"-O-methyl-4"-0-alkyl derivatives of 9-dehydro-3-0-propionyl-leucomycin V. Microbial glycosylation by a strain of Streptomyces hygroscopicus has been used to make the 2 -0-P-D-glucopyranosyl derivatives of erythromycin B, erythromycin A oxime and azithromycin. ... 

Fig. 6.1 Structure of the macrolide antibiotic erythromycin (a) which contains a 14-membeied lactone ring. The azalide, azithromycin (b), derived from erythromycin, has an iV-methyl group incorporated into the lactone ring, making it a 15-membered ring (compare highlighted sections)...

Erythromycin A, the major fermentation component of S. erythraea, is a 14-membered ring macrolide that is used by medicinal chemists as the foundation for building semisynthetic derivatives of erythromycin antibiotics. (Macrohdes inhibit bacteria by interfering with microbial protein biosynthesis.) Semisynthetic macrolides are popular with clinicians because they can be administered orally and have relatively low toxicity. They are often used to treat respiratory tract infections, and have been especially effective against conditions such as Legionnaires disease and community-acquired pneumonia. Erythromycin therapy is often prescribed for individuals allergic to penicillin. One of the most widely used macrohde antibiotics... 

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