A conformational NMR analysis of methymycin aglycones: complete and unambiguous assignments of stereochemically diverse glycosylated methymycin analogs by 1D and 2D NMR techniques and molecular modeling.
The (1)H and (13)C NMR spectra of 10-deoxymethynolide (1), 8.9-dihydro-10-deoxymethynolide (2) and its glycosylated derivatives (3-9) were analyzed using gradient-selected NMR techniques, including 1D TOCSY, gCOSY, 1D NOESY (DPFGSENOE), NOESY, gHMBC, gHSQC and gHSQC-TOCSY. The NMR spectral parameters (chemical shifts and coupling constants) of 1-9 were determined by iterative analysis. For the first time, complete and unambiguous assignment of the (1)H NMR spectrum of 10-deoxymethynolide (1) has been achieved in CDCl(3), CD(3)OD and C(6)D(6) solvents. The (1)H NMR spectrum of 8,9-dihydro-10-deoxymethynolide (2) was recorded in CDCl(3), (CD(3))(2)CO and CD(3)OD solutions to determine the conformation. NMR-based conformational analysis of 1 and 2 in conjugation with molecular modeling concluded that the 12-membered ring of the macrolactones may predominantly exist in a single stable conformation in all solvents examined. In all cases, a change in solvent caused only small changes in chemical shifts and coupling constants, suggesting that all glycosylated methymycin analogs exist with similar conformations of the aglycone ring in solution.
C. Eugene Bennett Department of Chemistry, West Virginia University, P.O. Box 6045, Morgantown, WV 26506-6045, USA. Novruz.Akhmedov@mail.wvu.edu
Novruz G
NG
Akhmedov
Peter M
PM
Gannett
Bulan
B
Wu
Matthew M
MM
Cummings
Brian C
BC
Train
D003903:Deuterium; D006031:Glycosylation; D006859:Hydrogen; D018942:Macrolides / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D008958:Models, Molecular; D008968:Molecular Conformation; D012015:Reference Standards; D013237:Stereoisomerism
D018942:Macrolides; C008517:methymycin; D006859:Hydrogen; D003903:Deuterium