Erythromycin derivatization

Another successhil strategy for derivatization of erythromycin employed modification of functional groups involved in intramolecular cyclizations. The C-9 ketone, C-6 hydroxyl group, C-8 proton, and/or C-ll,12-diol of erythromycin were converted into functional groups which participate poorly, if at all, in intramolecular cyclizations. Some derivatives which have been extensively evaluated in preclinical and clinical trials exhibit such desirable properties as better stabiUty under acidic conditions, greater oral bioavadabihty, and higher and more prolonged concentrations of antibiotic in semm and tissues. 

Advantages include in this CL system the reagent is regenerated and it can be recycled, and derivatization is not required for many classes of compounds. Many aliphatic amines such as alkylamines, amino acids, proteins, antibiotics such as erythromycin and clindamycin, and NADH, among others can par-... 

In liquid chromatographic analysis of macrolides and lincosamides, most popular is the ultraviolet detector (Table 29.4). Tylosin, tilmicosin, spiramycin, sedecamycin, and josamycin exhibit relatively strong ultraviolet absorption, but erythromycin, lincomycin, pirlimycin, and oleandomycin show extremely weak absorption in the ultraviolet region. Hence, detection at 200-210 nm has been reported for the determination of lincomycin (146). However, a combination of poor sensitivity and interference from coextractives necessitated extensive cleanup and concentration of the extract. Precolumn derivatization of pirlimycin with 9-fluorenylmethyl chloroformate has also been described to impart a chromophore for ultraviolet detection at 264 nm (140). 

Modern spectroscopic techniques have revolutionized compound identification and quantification. Only a few decades ago, identification of a structurally complex natural product would require multigram quantities of isolated material, which would then be subjected to series of derivatization and degradation experiments, aiming to deduce the unknown s structure from that of resulting derivatives or fragments that may represent known compounds. As a result of the tremendous advances in sensitivity and resolution of NMR spectroscopy over the past 30 years, identification of microgram quantities of new compounds has now become routine. For example, the structure of the polyketide antibiotic, erythromycin (1), was identified in 1957 only after extensive chemical and spectroscopic studies based on multigram amounts of isolated compound.1-3 By the time its... 

Zierfels, G. Petz, M. [Fluorimetric determination of erythromycin residues in foods of animal origin after derivatization with FMOC and HPLC separation]. Z.Lebensm.Unters.Forsch., 1994, 198, 307-312... 

The Sonogashira reaction can also be applied in quinoline halogens, attaching alkynes the quinoline ring. This method has been employed as an easy way to connect the quinoline pharmacophore tmit in interesting biological molecules as in the derivatization of 2-fluoro-6-0-propargyl-11,12-carbamate ketolide of erythromycin. ... 

Lewis CA, Miller SJ (2006) Site-selective derivatization and remodeling of erythromycin A by using simple peptide-based chiral catalysts. Angew Chem Int Ed 45 5616-5619... 

Four macrolide antibiotics (azithromycin, erythromycin, roxithromycin, clarithro-inycin) were extracted om serum, derivatized with FMOC-Cl, and separated on a 50°C base deactivated C,g column (A = 225 nm, ex 31Snm, em). A 40/60 water (SOmM KH2PO4 with SOOpL triethylamine/L to pH 7.5 with 10% KOH)/ acetonitrile mobile phase generated baseline resolution and complete elution in 22 min [1346]. Calibration curves of 0.1-20mg/mL and quantitation limits of 1-12 mg/L were reported. 

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