Determination of the aqueous-phase structure of 6-O-methylerythromycin from NMR constraints

The three-dimensional structure of the antibiotic 6-O-methylerythromycin in water was determined via constrained molecular mechanics using constraints derived from NMR spectra. The NMR structure is compared with its crystal structure and the structures of other derivatives of erythromycin. Distance constraints were obtained from NOESY, ROESY and GOESY spectra and torsional constraints from proton-proton and proton-carbon vicinal coupling constants. The modeling calculations employed Version 6.5 of SYBYL and the 1994 release of the Merck Molecular Force Field. The three-dimensional structure is defined by four structures that minimize the energy and satisfy all the experimental NMR data. It has the following characteristics: the macrolide ring adopts a folded-out conformation, the cladinose and desosamine rings adopt chair conformations, the cladinose ring is parallel to the plane of the macrolide ring and the desosamine ring is perpendicular to the macrolide ring. Copyright (C) 2001 John Wiley & Sons, Ltd.