Barakat Assem, Al-Majid Abdullah Mohammed, Soliman Saied M, Lotfy Gehad, Ghabbour Hazem A, Fun Hoong-Kun, Wadood Abdul, Warad Ismail, Sloop Joseph C
Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, Faculty of Science, Alexandria University, P. O. Box 426, Ibrahimia, Alexandria 21321, Egypt.
Molecules. 2015 Nov 19;20(11):20642-58. doi: 10.3390/molecules201119710.
The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229.
描述了通过N,N - 二乙基硫代巴比妥酸1对二烯酮2进行区域选择性迈克尔加成反应合成新的二乙基铵盐二乙基铵(E)-5-(1,5-双(4-氟苯基)-3-氧代戊-4-烯-1-基)-1,3-二乙基-4,6-二氧代-2-硫代六氢嘧啶-5-化物3的过程。在化合物3中,硫代巴比妥部分的碳负离子通过与相邻羰基的强分子内电子离域作用得以稳定,因此反应在没有任何环化的情况下进行。通过单晶X射线衍射以及DFT计算确定了化合物3的分子结构。理论计算(DFT/B3LYP)的几何结构与晶体学数据吻合良好。使用DFT方法研究了氯原子取代氟原子对分子结构方面的影响。计算得到的电子光谱表明,当氟被氯取代时,π-π*跃迁发生红移。进行了电荷分解分析以研究所研究体系中不同片段之间可能的相互作用。研究该化合物抑制性质的分子对接模拟显示其具有抗糖尿病活性,活性概率(Pa)值为0.229。