Pifferi G, Pinza M
Farmaco Sci. 1977 Aug;32(8):602-13.
In the event that the GABA-GABOB system is involved in the initial phases of the learning and memory process, some new derivatives of 4-hydroxy-2-pyrrolidinone (I a) have been synthesized. The cyclic compounds of general formula (A) are more lipophilic than GABOB and should better enter brain fluids. The N-hydroxymethyl derivatives (II a...c) were prepared by addition of the suitable aldehydes to 4-acetoxy-2-pyrrolidinone (I b). In order to obtain the ethyl 4-hydroxy-2-oxo-1-pyrrolidineacetate (IV a) some synthetic routes starting from (I b), (III b) and from the 3-diazotetramic acid (V) were explored. However, the N-ethoxycarbonylmethyltetramic acid (X), obtained by Dieckmann cyclization of triester (VIII) and subsequent de-etho-xycarbonylation was reduced to (IV a). Ammonolysis of (IV a) afforded the acetamide (XI a). The O-acetyl derivatives (IV b) and (XI b) were also prepared.
如果γ-氨基丁酸-γ-氨基丁醇（GABA-GABOB）系统参与学习和记忆过程的初始阶段，已合成了一些4-羟基-2-吡咯烷酮（I a）的新衍生物。通式（A）的环状化合物比GABOB具有更强的亲脂性，应该能更好地进入脑液。通过将合适的醛加成到4-乙酰氧基-2-吡咯烷酮（I b）上制备了N-羟甲基衍生物（II a...c）。为了得到4-羟基-2-氧代-1-吡咯烷乙酸乙酯（IV a），探索了一些从（I b）、（III b）和3-重氮四羰酸（V）出发的合成路线。然而，通过三酯（VIII）的迪克曼环化反应并随后脱乙氧基羰基化得到的N-乙氧羰基甲基四羰酸（X）被还原为（IV a）。（IV a）的氨解反应得到乙酰胺（XI a）。还制备了O-乙酰基衍生物（IV b）和（XI b）。
