The conformational analysis of derivatives of erythromycin A. X-Ray crystallographic and nuclear magnetic resonance spectroscopic studies of (E)-11-O-(2-dimethylaminoethoxy)methyl-9-deoxo-9-methoxyiminoerythromycin A

Abstract

(E)-11-O-(2-Dimethylaminoethoxy)methyl-9-deoxo-9-methoxyiminoerythromycin A (3) has been synthesised from erythromycin A (1) and its crystal structure conformation compared with that of (1). The conformations of the two sugars and their orientation with respect to one another are the same in (1) and (3). The conformations of the aglycones are, however, markedly different. In comparison with (1), the main conformational changes in (3) appear to be a folding in the aglyconie about the C-7 methylene and lactone ring oxygen, which moves the C-6 hydroxy and lactone carbonyl away from the substituents at C-9 and C-11, and an inward folding (towards C-11) of the C-3 to C-5 region and the attached sugars.

The conformation of (3) in CDCl₃ was investigated by measuring ¹H vicinal coupling constants, ¹H n.O.e.s, and ¹³C spin–lattice relaxation times. These studies show that in solution. (3) exists in a state of fast exchange between conformations of the C-3 to C-5 ‘folded out’ and C-3 to C-5 ‘folded in’ types. One of the simplest representations of this would be a rapid equilibrium between conformations similar to those found in the crystal structures of (1) and (3).