Oleandomycin analysis

In traditional electrophoresis, separation efficiency is limited by thermal diffusion and convection. Owing to long analysis times and low efficiencies, these procedures never enjoyed wide usage. Problems have arisen when trying to differentiate between structurally related drug residues such as streptomycin and dihydrostreptomycin, tetracyclines, lincomycin and clindamycin, and erythromycin and oleandomycin (83, 84). To overcome these problems, anticonvective media, such as polyacrylamide or agarose gels, have also been used. 

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). 

L. Rodriguez, D. Rodriguez, C. Olano, A. F. Brana, C. Mendez, and J. A. Salas, Functional analysis of OleY L-oleandrosyl 3-O-methyltransferase of the oleandomycin biosynthetic pathway in Streptomyces antibioticus, J. Bacteriol., 183 (2001) 5358-5363. 

It has been stated previously that the carbohydrate components of antibiotics have proved particularly amenable to analysis by n.m.r. spectroscopy. Thus, the structures of chalcose, desosamine, mycarose and cladinose have been established by n.m.r. spectroscopy. To this list may be added oleandrose, chromose " and arcanose. By making suitable model compounds it was possible to show that in oleandomycin, L-oleandrose exists in a 1-C conformation and has a a-L- linkage, whereas D-desosamine exists in a C-1 conformation and has a j3-D- anomeric linkage. 

The /hc and /hh couplings have been used by Novak et al in the conformational analysis of the 14-membered macrolide antibiotic oleandomycin and its 8-methylene-9-oxime derivative, and by Hayakawa et al in the structure elucidation of an antitumor antibiotic, tyroscherin (see also Table 3). 

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