13-Substituted erythromycin derivatives

Stassi, D.L., Kakavas, S.J., Reynolds, K.A. cl al. (1998) Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering. Proceedings of the National Academy of Sciences of the United States of America, 95, 7305. 

DL Stassi, SJ Kakavas, KA Reynolds, G Gunawardana, S Swanson, D Zeidner, M Jackson, H Liu, A Buko, L Katz. Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering. Proc Natl Acad Sci (USA) 95 7305-7309,... 

Ruan, X., Pereda, A., Stassi, D.L. et al. (1997) Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives. Journal of Bacteriology, 179, 6416. 

Ruan, X., Pereda, A., Stassi, D. L., Zeidner, D., Summers, R. G., Jackson, M., Shivakumar, A., Kakavas, S., Staver, M.J., Donadio, S., and Katz, L. (1997). Acyl transferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives./. Bacteriol., 179, 6416-6425. 

Keyes, R.F., Carter, J.J., Zhang, X. and Ma, Z. (2005) Short and efficient synthesis of a vinyl-substituted tricyclic erythromycin derivative. Organic Letters, 7, 847-849. 

Clindamycin is a chlorine-substituted derivative of lincomycin. However it is more potent and is better absorbed from the gastrointestinal tract and has therefore replaced lincomycin in most situations. Clindamycin is in principle a bacteriostatic agent. Its indications are mainly limited to mixed anaerobic infections. As mentioned above it has a similar mechanism of action as erythromycin. It selectively inhibits bacterial protein synthesis by binding to the same 50s ribosomal subunits. Erythromycin and clindamycin can interfere with each other by competing for this receptor. Also cross-resistance with erythromycin frequently occurs. Resistance is rather chromosomal rather than plasmid mediated and is especially found in cocci and Clostridium difficile. 

Clindamycin is a chlorine-substituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis. Lincomycin, although structurally distinct, resembles erythromycin in activity, but it is toxic and no longer used. 

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... 

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