C-2 epimerisation in an erythromycin derivative. Preparation and NMR spectrocopic studies on (2S)-(E)-9-deoxo-9-methoxyiminoerythromycin A

Abstract

(2S)-(E)-9-Deoxo-9-methoxyiminoerythromycin A 9 has been prepared and characterised by NMR spectroscopy, including NOE experiments. In solution, 9 appears to adopt only the C-3 to C-5 ‘folded out’ conformation. This is in contrast to (E)-9-deoxo-9-methoxyiminoerythromycin A 8, itself, which exists in solution as a mixture of ‘folded out’(major) and ‘folded in’(minor) conformations in fast exchange. Epimerisation experiments suggest that, for the derivatives studied here, he 2-epi(2S) configuration is thermodynamically less stable than the natural (2R) configurations. The relative stabilities of the various configurations and conformations suggested by these experiments are supported by molecular mechanics calculations.