Erythromycin B and

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. 

L D. Doxycycline is the preferred parenteral tetracycline for the primary state of Lyme disease in adults and children older than 8 years of age. Penicillin V (A) would be ineffective. Erythromycin (B) and clarithromycin (C) also are not effective against Borrelia burgdorferi, the gram-negative anaerobe organism responsible for Lyme disease. 

An antimicrobial substance produced by the growth of certain strains of Streptomyces erythreus. It is a mixture consisting largely of erythromycin A with lesser amounts of erythromycins B and C. 

Chloroethyl chloroformate, EtOAc, 7 eq. 50°C, 5 h followed by treatment with methanol which removes the carbamate by solvolysis. This method was used to cleave the IV-methyl from erythromycin B and in the synthesis of a series of Strychnos alkaloids. ... 

Antibiotics. - Reversed-phase h.p.l.c. analyses have been reported for the following dialkylamino-sugar-containing antibiotics the anthracycline glycoside 3 -deamino-3 -[2(S)-methoxy-4-morpholinyl]doxorubicin and its possible 13-dehydro-metabolite, the macrolide antibiotics rokitamycin and josamycin as their dansylhydrazone derivatives. In addition, erythromycin ethyl succinate and its process impurities erythromycin A, the ethyl succinate esters of erythromycin B and C and A-(ethyl succinyl)-iV-demethyletythromycin A were analyzed by ion-pair reversed-phase h.p.l.c. ... 

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. 

FIG. 19 Chemical structures of (a) erythromycin, (b) chloramphenicol, (c) ampicillin, (d) cefpo-doxime proxetil, and (e) doxycycline hydrochloride. 

Tsuji and Goetz24 developed a quantitative high performance liquid chromatographic method for separating and measuring erythromycins A, B, and C, their epimers and degradation products. This method uses a /iBondapak Ci 8 reverse column with acetonitrile-methanol-O.2m ammonium acetate-water (45 10 10 25) as solvent. The pH and composition of the mobile phase may be adjusted to optimize resolution and elution volume. The authors utilized the procedure on USP reference standard and report a relative standard deviation of 0.64%. 

The most impressive application of 2-thiopyridyl and 2-thiopyrimidinyl donors is in the area of antibiotics. Thus, Woodward et al. [481] successfully completed the total synthesis of erythromycin by using S Pyrm glycoside of D-desosamine and S Pyr-glycoside of L-cladinose as glycosyl donors to the subsequent glycosylation with erythronalide A. This methodology was also successfully used in the synthesis of oleandomycin [482,483], erythromycin A [484] and erythromycin B [485]. 

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.)... 

Admixture incompatibility Tetracycline, chlortetracycline, oxytetracycline, erythromycin lactobionate, amphotericin B, and sodium ampicillin are incompatible when mixed in the same solution with acetylcysteine. Administer from separate... 

Erythromycin and oleandomycin are examples with a 14-membered ring. The former is a mixture of three closely related compounds erythromycin A, B, and C erythromycin A is the major and most important component. The latter consists of a single component. 

Macrolides. Antibiotics in the macrolide group are macrocyclic lactones that can be further classified into two main subgroups (I) polyene macrolides that are antifungal agents and include compounds like nystatin and amphotericin B and (2) antibacterial antibiotics represented by erythromycin and tylosin. A number of other subfamilies of antibacterial and antifungal antibiotics fall into the broad category of macrolides,... 

Godin, B., and E. Touitou. 2005. Erythromycin ethosomal systems Physicochemical characterization and enhanced antibacterial activity. Curr Drug Deliv 2 269. 

S. Donadio, M. J. Staver, J. B. McAlpine, S. J. Swanson, and L. Katz, Biosynthesis of the erythromycin macrolactone and a rational approach for producing hybrid macrolides, Gene, 115 (1992) 97-103. 

B. Erythromycin, Rapamycin, and Other Modular Polyketide Synthases... 

Triazolam plasma concentrations were determined by gas chromatography with electron capture detection (73,95). The pharmacokinetic results demonstrated that mean clearance during Trials B and C were nearly identical (413 and 416 mL/min, respectively) that is, coadministration of azithromycin had no effect on the pharmacokinetics of triazolam (Fig. 5). However, triazolam clearance was significantly reduced to 146 mL/min by erythromycin (Trial D) and to 95 mL/min by clarithromycin (Trial E). Thus, the in vivo kinetic results are highly consistent with the in vitro data. 

The pharmacodynamic data indicated that the benzodiazepine agonist effects of triazolam plus placebo (Trial B) and of triazolam plus azithromycin (Trial C) were similar to each other and greater than the effects of placebo plus placebo (Trial A). However, coadministration of erythromycin (Trial D) or... 

Aminophylline Aminophylline should not be mixed with acidic drugs, as it becomes precipitated if the pH of the final solution falls below pH 8. Mixture with glucose may increase the pH above 10 where proteins, such as insulin and erythromycin, are unstable. Some drugs that are incompatible with aminophylline include amiodarone, benzylpenicillin potassium, cisatracurium, ceftazidime, ceftriaxone, dobutamine, tetracycline hydrochloride, verapamil hydrochloride, warfarin sodium, and vitamin B and C injection. Alcohol-free theophylline should be stored in amber-colored containers maximum care must be taken to protect it against exposure to light.92-94... 

Two superior, alternative reagents for the Corey method are the disulfides 23 and 24 [19], For example, in the first synthesis [20] of erythronolide B (27), the aglycone of the important antibiotic erythromycin B, cyclization of the hydroxy acid 25 to the 14-membered lactone 26 was effected in 50% yield via the thiol ester of 4-r-butyl-iV-isopropyl-2-mercaptoimidazole by heating in dry toluene under reflux (Scheme 9). 

Chlamydial conjunctivitis. In the developed world, the genital (D-K) serotypes of the organism are responsible and the reservoir and transmission is maintained by sexual contact. Endemic trachoma in developing countries is usually caused by serotypes A, B and C. In either case, oral tetracycline is effective. Pregnant or lactating women may receive sys-teiiuc erythromycin. Neonatal ophthalmia should be treated with systemic erythromycin and topical tetracycline. 

Kochetkov and coworkers synthesized erythronolides A (20) and B (21) via a different route [26,27,28]. There have been many reports on the syntheses of erythromycin. Among them, four examples are the Yonemitsu synthesis of erythronolide A (20) [29,30], featuring an extremely efficient macrocyclization (the modified Yamaguchi method) Martin s synthesis of erythromycin B (19) [31,32] Evans synthesis of 6-deoxyerythronolide B [33,34], featuring the aldol-based assemblage of each synthetic segment and the Carreira synthesis of erythronolide A (20), featuring the Mg-mediated cycloadditions of nitrile oxides [35]. 

The commercial product is erythromycin A. which differs from its bio.syntlietic precursor, erythromycin B, in having a hydroxyl group at the 12 position of the aglycone. The chemical structure of erythromycin A was reported by Wiley et al. in I9.S7 and its stereochemistry by Celmer in 1965. An elegant synthesis of erythronolidc A, the aglycone pre.sent in erythromycin A. wa.s described by Corey and associates. ... 

Siedlik, P.H., Olson, S.C.. Yang. B.B.. and Stern, R.H. (1999) Erythromycin coadministration increases plasma atorvastatin concentrations. Journal of Clinical Pharmacology, 39, 501-504. 

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