Erythromycin A and

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. 

FIGURE 10 Isocratic CEC of erythromycin A and its impurities. Cationic column 30cm (effective length 20 cm) x 50 pm ID mobile phase 25% (v/v) acetonitrile and 25% (v/v) ethanol in 30mM phosphate buffer, pH 8.0 applied voltage — l5kV detection, 206 nm. Sample (I) N-demethylerythromycin A, (2) erythromycin C, (3) erythromycin A, (4) erythromycin B, (5) erythromycin enol ether. Mobility of EOF measured with DMSO, peof = 3-33 x 10 °m /sV. (Reprinted from reference 321, with permission.)... 

In many cases, biotechnology-derived products may have many components that have biological activity. The aim should be to devise controls that monitor the various components so as to retain a consistent potency and purity. For example, the USP monograph for erythromycin [9] indicates that the principal component is erythromycin A and that the percentage of erythromycin A, erythromycin B, and erythromycin C is not less than 85.0% and not more than 100.5%. Within these parameters, the relative ratios of erythromycins A, B, and C may change. This is not always the case for biotechnology-derived products, however. For example, the USP monograph for amoxicillin [10] allows for only one active component. 

Coupling of LC with either ISP-MS or ISP-MS-MS has been also investigated as an attractive alternative for the determination of erythromycin A and its metabolites in salmon tissue (122). The combination of these methods permitted identification of a number of degradation products and metabolites of erythromycin, including anhydroerythromycin and N-demethyerythromycin at the level of 10-50 ppb. 

A new strategy for the synthesis of erythromycin A and closely related mac-rolide antibiotics was elaborated in our laboratory (88). This new approach to synthesis is based on the knowledge that stereoelectronic effects control the conformation of acetals. The strategy is based on the 1,7-dioxaspiro-[5.5]undecane system which was found to be conformationally rigid, existing in conformation J50 only (see Chapter 2). This is so because in this confor-mation, steric effects are at their minimum and the acetal function has... 

J. Paesen, E. Roets, and J. Hoogmartens, Liquid chromatography of erythromycin A and related substances on poly(styrene-dinvinyl benzene), Chromatographia, 32 162(1991). 

A three-column ion-exchange and reversed-phase system has been developed for the assay of enprostil in soft elastic gelatin capsules [336]. A two-column approach has also been used to resolve D,L-amino acids in complex matrices [337]. Erythromycin A and its known impurities were resolved using two C18 columns [338]. 

The enzyme converts erythromycin C into erythromycin A in the presence of AdoMet. Evidence was obtained that the enzyme is associated with the microsomal fraction. The enzyme showed a very high degree of substrate specificity. Aside from erythromycin C, it failed to catalyze the methylation of any other L-mycarosyl moiety tested. Erythromycin A and S-adenosyl-L-homocysteine (AdoHcy) were potent inhibitors of the enzyme, and it was assumed that the Ado-Met AdoHcy ratio could be a major regulatory factor of the final step in the formation of erythromycin A. 

Oleinick, N.L., Wilhelm, J.M., Corcoran, J.W., Nonidentity of the site of action of erythromycin A and chloramphenicol on Bacillus subtilis ribosomes. Biochim. Biophys. Acta 1967, 155, 290-292. 

Pleasance et al. [23] described residue analysis of erythromycin A and its metabolites in salmon tissue using LC-ESl-MS. Detection limits of erythromycin A in salmon tissue were below 10 pg/kg in SIM and below 50 pg/kg in SRM, while confirmatory full-scan LC-MS or LC-MS-MS was achieved at the 0.5- and 1-mg/kg level, respectively. Next to erythromycin A, a variety of metabolites were detected, e.g., anhydroerythromycin and N-desmethylerythromycin. 

Liquid chromatography-ionspray-mass spectrometry has been shown to be an attractive approach for the determination of semduramicin in chicken liver. Tandem MS using the CID of the molecular ions further enhanced the specificity providing strucmre elucidation and selective detection down to 30 ppb. Liquid chromatography-ionspray-mass spectrometry has also been successfully applied for the assay of 21 sulfonamides in salmon flesh. Coupling of LC with either ISP-MS or ISP-MS-MS has also been investigated as an attractive alternative for the determination of erythromycin A and its metabolites in salmon tissue. The combination of these methods permitted the identification of a number of degradation products and metabolites of erythromycin at the 10-50 ppb level. Tandem MS with CID has also been... 

Cane has demonstrated that advanced di-, tri- and tetraketide fatty acid precursors are incorporated directly into the nargeiucins, and has noted that an early intermediate in the nargenicin pathway is common to the biosynthetic scheme leading to erythromycin A and... 

Nishida. A.. Yagi, K., Kawahara, N., Nishida, M., and Yonemitsu, ()., Chemical modification of erythromycin A. Synthesis of the C1-C9 fragment from erythromycin A and reconstruction of the macrolactone ring. Tetrahedron Lett., 36, 3215, 1995. 

Pyrolysis of the JV-oxides of erythromycin A and B gave products containing dihydropyranyl residues, from which methyl 3,4,6-tri-deoxy-hex-3-enopyranosides were obtained by methanolysis.1248... 

Figure 118. Acid degradation of showing the stabilizing effect of substitution of a methoxy for a hydroxy group, erythromycin (a) and clarithromycin (b) at 37°C. (Reproduced from Ref. 508 with permission.)...

Antibacterial Activities and Gastric Motor Stimulant Activities of Erythromycin A and Its Derivatives... 

O-Methylmycarose, CgHl60, Cladinose. Constituent of erythromycin A and B. Liquid, bp at bath temp 120-132°. [< ], — 23. l (c = 2.6 in water), Sol in water, alcohol, acetone, ether, benzene, chloroform, carbon tetrachloride slightly so) in petr ether. Dec by strong acids. 

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. ... 

Khan, K. Paesen, J. Roets, E. Hoogmartens, J. Analysis of erythromycin A and its metabolites in biological samples by liquid chromatography with post-column ion-pair esdraction. J.Liq. Chromatogr., 1994, 17, 4195—4213... 

Natural Products as Substrates Studies of the Relative Reactivity and Remote Functionalization of the Hydroxyl Groups of Erythromycin A and Apoptolidin A... 

Fig. 3 Structures of erythromycin A and apoptolidin A. Potentially reactive hydroxyls are shown in red...

Fig. 8.4 Macrolide antibiotics originating from erythromycin A and their hydroxylated derivatives produced by P450...

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