Naslov
Conformational analysis of oleandomycin and its 8-methylene-9-oxime derivative by NMR and molecular modeling

Autori
Novak, Predrag ; Banić Tomišić, Zrinka ; Tepeš, Predrag ; Lazarevski, Gorjana ; Plavec, Janez ; Turkalj, Gordana

Izvornik
Organic and Biomolecular Chemistry (1477-0520) 3 (2005), 1; 39-47

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
macrolide antibiotic; oleandomycin; conformation; NMR; molecular modeling

Sažetak
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. A predominant conformation of 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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA