Novel unsaturated piperazine and homopiperazine derivatives (3a–h) were synthesized in medium to good yields by acylation reactions of piperazine and homopiperazine with methacrylic anhydride (2a) and benzoyl chloride (2b). Piperazine containing dihydrofuran compounds (5a–l) were obtained from radical addition and cyclizations of 3a–h with 1,3-dicarbonyl compounds such as dimedone (4a), ethyl acetoacetate (4b) and acetylacetone (4c) mediated by Mn(OAc)₃ for the first time. While the reaction of 3b (1-methacryloylpiperazine) with 4a and 4b gave bis-dihydrofurans (5b and 5d) beside mono-dihydrofurans (5a and 5c), the reaction of 3b–e, 3g, 3h, and 3e with 1,3-dicarbonyl compounds gave mono dihydrofuran compounds (5f–l) in medium to high yields. Structures of all novel compounds were determined by melting point analysis, ¹H NMR, ¹³C NMR, HRMS, and FTIR methods. All piperazine containing dihydrofuran compounds were evaluated for their inhibitory activities toward acetylcholinesterase (AChE) by Ellman method and IC₅₀ values were presented. Compounds 5c, 5d, 5e, 5i, and 5l show highest inhibitory activities with IC₅₀ values of 5.79, 3.89, 5.07, 4.30, and 2.24 µM, respectively. In addition, molecular docking studies were performed on selected structures 5d, 5i, and 5l to investigate ligand–protein interactions. Binding energies were calculated and compared with standart drug donepezil.

中文翻译：

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新哌嗪取代的二氢呋喃化合物的合成，表征，乙酰胆碱酯酶抑制和分子对接研究

通过哌嗪和高哌嗪与甲基丙烯酸酐（2a）和苯甲酰氯（2b）的酰化反应，以中等至高收率合成了新型不饱和哌嗪和高哌嗪衍生物（3a–h ）。含哌嗪的二氢呋喃化合物（5a–l）是通过自由基加成和3a–h与1,3-二羰基化合物（如二甲酮（4a），乙酰乙酸乙酯（4b）和乙酰丙酮（4c））的环化作用而得到的，其中Mn（OAc）第一次₃。而3b（1-甲基丙烯酰基哌嗪）与4a和4b的反应得到单二氢呋喃（5a和5c）旁边的双二氢呋喃（5b和5d），在介质中3b-e，3g，3h和3e与1,3-二羰基化合物的反应得到单二氢呋喃化合物（5f-1）高产。通过熔点分析，¹ H NMR，¹³ C NMR，HRMS和FTIR方法确定所有新化合物的结构。通过Ellman方法评估了所有含哌嗪的二氢呋喃化合物对乙酰胆碱酯酶（AChE）的抑制活性，并给出了IC ₅₀值。化合物5c，5d，5e，5i和5l表现出最高的抑制活性，IC ₅₀值分别为5.79、3.89、5.07、4.30和2.24 µM。此外，对选定的结构5d，5i和5l进行了分子对接研究，以研究配体与蛋白质的相互作用。计算结合能并将其与标准药物多奈哌齐进行比较。