STUDIES ON THE STRUCTURES OF MEROPENEM(SM-7338) AND ITS PRIMARY METABOLITE

The structure and solution conformation of meropenem was examined by using H-1 and C-13 NMR spectroscopy and nuclear Overhauser enhancement experiments. Similar to the X-ray crystal structure, the close spacing of 1beta-methyl substituent to the beta-lactam ring and the accessible conformation of C-2 side chain in relation to the carbapenem skeleton was confirmed. The structure of the primary metabolite of meropenem by dehydropeptidase-I was shown to be the beta-lactam ring-opened product by comparing the spectroscopic data with those of meropenem, and confirmed by the preparation and structural analysis of its crystalline derivative. This metabolite existed as a mixture of 1-pyrroline and 2-pyrroline isomers, and the coexistence of two isomers at equilibrium in aqueous solution was observed by NMR.