Studies on the structures of meropenem(SM-7338) and it's primary metabolite.
The structure and solution conformation of meropenem was examined by using 1H and 13C NMR spectroscopy and nuclear Overhauser enhancement experiments. Similar to the X-ray crystal structure, the close spacing of 1 beta-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.
Takeuchi
Y
Y
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Inoue
T
T
Sunagawa
M
M
D000818:Animals; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D000077731:Meropenem; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine; D013845:Thienamycins / Q000737:chemistry* / Q000378:metabolism
D013845:Thienamycins; C081743:2-methylthiocarbapenem; D000077731:Meropenem