Edafiogho I O, Moore J A, Alexander M S, Scott K R
Department of Medicinal Chemistry, College of Pharmacy and Pharmacal Sciences, Howard University, Washington, D.C. 20059.
J Pharm Sci. 1994 Aug;83(8):1155-70. doi: 10.1002/jps.2600830817.
1H nuclear magnetic resonance (NMR) spectra of enaminones were determined and compared to the anticonvulsant activity of the compounds. Although the precise employment of the NMR data to predict anticonvulsant activity of the enaminones could not be established, general inferences were made. The NMR data confirmed that the enaminones existed predominantly in the amino tautomer, and no evidence was found for the imino tautomer. The ketamine form of the enaminones was supported by the observed spin-spin splittings of the NH with the alpha-protons on certain enaminones. The NH of secondary enaminones was very important in conferring anticonvulsant activity to the enaminones. The peak for the NH proton which could be seen between delta (ppm) 4.50 and 9.70 was present in all of the active enaminones. The tertiary enaminones, which were devoid of the NH proton, were uniformly inactive. It appeared that a combination of steric and electronic effects, lipophilicity, and hydrogen bonding were necessary for the anticonvulsant activity of the enaminones. The cyclic enaminones existed in the trans-S-trans fixed conformation, and the NMR data supported our hypothesis that enantioselectivity is retained in synthesizing enaminones from cyclic, diasteriomeric 1,3-diketones. In addition, the AB system and many unique features were observed in some enaminones. The para, meta, and ortho substituted patterns were observed for monosubstituted phenyl protons, and the NMR patterns for di- and trisubstituted phenyl groups were elucidated.
测定了烯胺酮的¹H核磁共振（NMR）光谱，并将其与化合物的抗惊厥活性进行比较。尽管无法确定利用NMR数据精确预测烯胺酮的抗惊厥活性，但还是得出了一些一般性推论。NMR数据证实烯胺酮主要以氨基互变异构体形式存在，未发现亚氨基互变异构体的证据。某些烯胺酮上NH与α-质子之间观察到的自旋-自旋分裂支持了烯胺酮的氯胺酮形式。仲烯胺酮的NH对于赋予烯胺酮抗惊厥活性非常重要。在所有活性烯胺酮中均出现了δ（ppm）4.50至9.70之间可见的NH质子峰。不含NH质子的叔烯胺酮均无活性。似乎空间和电子效应、亲脂性和氢键的组合对于烯胺酮的抗惊厥活性是必需的。环状烯胺酮以反式-S-反式固定构象存在，NMR数据支持了我们的假设，即在由环状非对映体1,3-二酮合成烯胺酮时保留了对映选择性。此外，在一些烯胺酮中观察到了AB系统和许多独特特征。观察到单取代苯基质子的对位、间位和邻位取代模式，并阐明了二取代和三取代苯基的NMR模式。
