Takeuchi Y, Inoue T, Sunagawa M
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1993 May;46(5):827-32. doi: 10.7164/antibiotics.46.827.
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.
通过使用1H和13C NMR光谱以及核Overhauser增强实验研究了美罗培南的结构和溶液构象。与X射线晶体结构相似，证实了1β-甲基取代基与β-内酰胺环的紧密间距以及C-2侧链相对于碳青霉烯骨架的可及构象。通过将光谱数据与美罗培南的光谱数据进行比较，显示美罗培南经脱氢肽酶-I作用后的主要代谢产物的结构为β-内酰胺环开环产物，并通过其结晶衍生物的制备和结构分析得到证实。该代谢产物以1-吡咯啉和2-吡咯啉异构体的混合物形式存在，并且通过NMR观察到两种异构体在水溶液中处于平衡状态共存。
