Erythromycin structure

Bauer, J. Quick, J. Oheim, R.J. Alternate interpretation of the role of water in the erythromycin structure. Pharm. Sci. 

Figure 5 Erythromycin structure and position of O-methylation for obtaining increased lung uptake.

Figure 10.2 The reversible CYP3A4 inhibitor and antifungal drug ketoconazole, the irreversible CYP3 A4 inhibitor and proestrogen drug gestodene, and the quasi-irreversible CYP3A4 inhibitor and antibacterial drug erythromycin. Structural features key to their CYP inhibition are shown in blue.

CHEMISTRY OF ERYTHROMYCIN Structure and physical-chemical data Total synthesis Intramolecular cyclization... 

Erythromycins from Streptomyces erytkreua strains are probably the structurally most complex of the best selling drugs. Erythromycin A costs only about 5 DM per gram. The two principal erythromycins A and B differ only with respect to hydroxylation at C-12. 

NMR, 4, 575 Erythritol, 1,4-anhydro-structure, 4, 546 Erythromycin antibacterial veterinary use, 1, 206 as pharmaceutical, 1, 153 synthesis, 1, 480 Erythropterin biosynthesis, 3, 321 occurence, 3, 323 structure, 3, 276 synthesis, 3, 289 Erythropterin, 3,5-dimethyl-methyl ester synthesis, 3, 303 Erythrosine application, 3, 879 Esculetin... 

Structural Formula See Erythromycin for structure of base. Chemical Abstracts Registry No. 3847-29-8... 

The fungus Streptomyces erythreus is the source of a number of structurally related macrolide antibiotics that are collectively known as the erythromycins. The erythromycins occupy a prominent position in medicine by virtue of their useful antibacterial properties. Their use in therapy over the course of the last three decades has been widespread, and has resulted in the saving of many human lives. In this chapter, we address the landmark total synthesis of erythronolide B (1), the biosynthetic precursor of all the erythromycins, by E.J. Corey and his coworkers which was carried out at Harvard in the 1970s.1... 

Challenged and inspired by the complex structures of the erythromycins, Corey s group developed a novel, efficient, and general... 

Natural product total syntheses are particularly valuable when they are attended by the development of general utility methods of synthesis. In some instances, the successful completion of a natural product total synthesis requires the development and application of a new synthetic method. The total synthesis of erythronolide B by Corey et al. is one of these instances. The double activation macro-lactonization method was a fruitful innovation that was introduced in response to the challenge presented by the macrocyclic structures of the erythromycins. Several other methods to achieve the same objective, and numerous applications followed. 

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. 

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. 

FIGURE 4.20 Structures of the CYP3A4 substrates, erythromycin, nifedipine, testosterone, and midazolam, and their metabolites. 

There are six crystal structures reported in the Protein Data Bank two without ligand (ltqnand IwOe), one cocrystallized with progesterone (7) (IwOf), one with mytrapone (8) (IwOg), one with ketoconazole (9) (2j0c) and one with erythromycin (10) (2j0d). 

Yong D, Toleman MA, Giske CG et al (2009) Characterization of a new metallo-beta-lactamase gene, bla(NDM-l), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53(12) 5046-5054... 

Another basic drug where minor structural modification results in a dramatic increase in volume of distribution is the macrolide antibiotic, azithromycin. The traditional agent in this class is erythromycin, which contains one basic nitrogen, in the sugar side-chain. 

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

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