“…The HSQC spectra yielded an unambiguous assignment for the protonated carbon atoms, while correlation peaks in HMBC spectra revealed information about the quaternary carbons and confirmed the assignments of the protonated carbons. The values obtained in CDCl 3 are in good agreement with those reported previously . The chemical shifts obtained in acetone- d 6 and DMSO- d 6 (Table ) are similar to those in CDCl 3 .…”
Section: Resultssupporting
confidence: 90%
“…Oleandomycin ( 1 ) and its derivatives oleandomycin-9-oxime ( 2 ) and 10,11-anhydrooleandomycin ( 3 ) (Figure ) consist of a 14-membered macrocycle ring and two cyclic sugars, oleandrose and desosamine. , Oleandomycin differs from erythromycin by the exocyclic epoxide at C8, being a unique feature without being equal in any other known polyoxo macrolide. 1 Compounds studied and the atom numbering.…”
The three-dimensional structures of oleandomycin (1) and its derivatives oleandomycin-9-oxime (2) and 10,11-anhydrooleandomycin (3) were determined in different solvents by the combined use of NMR and molecular modeling methods. The experimental NMR data were compared with the results of molecular modeling and known crystal structures of the related molecules. It was shown that the dominant conformation of the lactone ring is the folded-out conformation with some amounts of the folded-in one depending on the solvent and temperature, while desosamine and cladinose sugars adopt the usual chair conformations. Modeling calculations provided evidence for conformational changes in the upper lactone region as well. Saturation transfer difference (STD) NMR experiments have provided information on the binding epitopes of 1-3 in complexes with E. coli ribosomes. The obtained molecular surfaces in close contact with ribosomes were compared with recently available 3D structures of the related macrolide-ribosome complexes, and the observed differences were discussed. The knowledge gained from this study can serve as a platform for the design of novel macrolides with an improved biological profile.
“…The HSQC spectra yielded an unambiguous assignment for the protonated carbon atoms, while correlation peaks in HMBC spectra revealed information about the quaternary carbons and confirmed the assignments of the protonated carbons. The values obtained in CDCl 3 are in good agreement with those reported previously . The chemical shifts obtained in acetone- d 6 and DMSO- d 6 (Table ) are similar to those in CDCl 3 .…”
Section: Resultssupporting
confidence: 90%
“…Oleandomycin ( 1 ) and its derivatives oleandomycin-9-oxime ( 2 ) and 10,11-anhydrooleandomycin ( 3 ) (Figure ) consist of a 14-membered macrocycle ring and two cyclic sugars, oleandrose and desosamine. , Oleandomycin differs from erythromycin by the exocyclic epoxide at C8, being a unique feature without being equal in any other known polyoxo macrolide. 1 Compounds studied and the atom numbering.…”
The three-dimensional structures of oleandomycin (1) and its derivatives oleandomycin-9-oxime (2) and 10,11-anhydrooleandomycin (3) were determined in different solvents by the combined use of NMR and molecular modeling methods. The experimental NMR data were compared with the results of molecular modeling and known crystal structures of the related molecules. It was shown that the dominant conformation of the lactone ring is the folded-out conformation with some amounts of the folded-in one depending on the solvent and temperature, while desosamine and cladinose sugars adopt the usual chair conformations. Modeling calculations provided evidence for conformational changes in the upper lactone region as well. Saturation transfer difference (STD) NMR experiments have provided information on the binding epitopes of 1-3 in complexes with E. coli ribosomes. The obtained molecular surfaces in close contact with ribosomes were compared with recently available 3D structures of the related macrolide-ribosome complexes, and the observed differences were discussed. The knowledge gained from this study can serve as a platform for the design of novel macrolides with an improved biological profile.
“…Reductive deoxygenation of C8 epoxide generated 8-methylene oleandomycin which, after treatment with hydroxylamine, gave an 8-methylene-9-oxime derivative 2 2 (Scheme 1). A literature search has shown a lack of information concerning the conformational characteristics of oleandomycin and oleandomycin-like compounds except for four X-ray structures, 3-6 three of which (1a, 3 2 6 and 3, 5 Scheme 1) are available through the Cambridge Structural Database 7 (CSD). The conformational behaviour of the related macrolide antibiotics such as erythromycin A, roxithromycin, clarithromycin, and azithromycin has been studied intensively 8- 15 by NMR and molecular modelling methods and by single-crystal X-ray analysis.…”
Conformations of the 14-membered macrolide antibiotic oleandomycin and its 8-methylene-9-oxime derivative were determined in various solvents. The experimental NMR data--coupling constants and NOE contacts--were compared with the results of molecular modelling--molecular mechanics calculations and molecular dynamics simulations. The conformational changes, on the right-hand side of the 14-membered ring, affected mostly the 3JH2,H3 values and NOE crosspeaks H3 or H4 to H11. Oleandomycin was found to be present predominantly in the C3-C5 folded-in conformations in DMSO-d6 solution, whereas in buffered D2O, acetone-d6 and CDCl3, there was a mixture of folded-in and folded-out conformational families. The predominant conformation of the 8-methylene-oleandomycin-9-oxime derivative in solution was a folded-out one although different amounts of folded-in conformation were also present depending on the solvent. Oleandrose and desosamine sugar moieties adopted the usual and expected chair conformation. The conformation around the glycosidic bonds, governing the relative orientation of sugars vs. the lactone ring, showed a certain flexibility within two conformationally close families. We believe that by combining the experimental NMR data and the molecular modelling techniques, as reported in this paper, we have made significant progress in understanding the conformational behaviour and properties of macrolides. Our belief is based on our own current studies on oleandomycins as well as on the previously reported results and best practices concerning other macrolides. A rational for macrolide conformational studies and advances in methodology has been suggested accordingly.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
