Abstract：
The molecular electron density theory (MEDT) was employed to examine the [4 + 2] cycloaddition reaction between (E)-N-((dimethylamino)methylene)benzothioamide (1) and (S)-3-acryloyl-4-phenyloxazolidin-2-one (2) at the B3LYP/6-311++G(d,p) design level. Parr functions and energy studies clearly show that this reaction is regio- and stereoselective, in perfect agreement with experimental results. By evaluating the chemical mechanism in terms of bond evolution theory (BET) and electron localization function (ELF), which divulges a variety of variations in the electron density along the reaction path, a single-step mechanism with highly asynchronous transition states structures was revealed. Additionally, we conducted a docking study on compounds P1, P2, P3, and P4 in the SARS-CoV-2 main protease (6LU7) in comparison to Nirmatrelvir. Our findings provide confirmation that product P4 may serve as a potent antiviral drug.
摘要：
分子电子密度理论（MEDT）用于检查（E）-N-（（二甲基氨基）亚甲基）苯并硫酰胺（1）和（S）-3-丙烯酰基-4-苯基恶唑烷-2-酮（2）在B3LYP/6-311++G（d，P)设计水平。Parr功能和能量研究清楚地表明，该反应是区域选择性和立体选择性的，与实验结果完全一致。通过从键演化理论（BET）和电子局域函数（ELF）方面评估化学机理，它沿着反应路径传播电子密度的各种变化，揭示了具有高度异步过渡状态结构的单步机制。此外,与Nirmatrelvir相比，我们对SARS-CoV-2主要蛋白酶（6LU7）中的化合物P1，P2，P3和P4进行了对接研究。我们的发现证实了产品P4可以作为一种有效的抗病毒药物。
