Solvent Directed Diastereodivergent Synthesis of Spiro-Oxindoles with Quaternary Carbon Center Forming

An efficient method has been developed for the solvent-directed diastereodivergent cyclization reactions with quaternary center formation. Various spiro-oxindole diastereoisomers were synthesized with good yields (up to >99 %) and moderate to high diastereoselectivities (up to >20 : 1). Further study on NMR studies indicates that the key to this approach lies in different interactions between the substrate and organocatalyst across diverse solvents. This methodology may have significant implications for switchable, solvent-directed diastereodivergent synthesis.     

A new eco-friendly strategy for the synthesis of novel antimicrobial spiro-oxindole derivatives via supramolecular catalysis

Novel spiro-oxindole derivatives were synthesised by one-pot multicomponent reaction using isatins, urea and 1,3-dicarbonyls. β-Cyclodextrin, an oligosaccharide, catalysed the reaction and can be reused for further reaction after recovery. This developed synthetic route is environmentally benign in which water is used as solvent to produce excellent yields of products. The synthesised compounds were evaluated for their antimicrobial activities against two bacteria and two fungi. All the synthesised spiro-oxindoles exhibit significant antimicrobial activity.     

螺环吲哚类MDM2抑制剂的分子对接、定量构效关系和分子动力学模拟

采用分子对接、三维定量构效关系(3D-QSAR)和分子动力学方法研究了21个螺环吲哚类化合物与MDM2蛋白的相互作用, 并建立了相关预测模型. 比较分子场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)模型的交互验证相关系数q²分别为0.573 和0.651, 非交互验证相关系数r²分别为0.948和0.980. 分子对接得到的结合模式与分子动力学模拟得到的结果一致, 结合模式表明该类螺环吲哚化合物主要通过疏水相互作用和氢键与MDM2结合. 基于上述相互作用模型设计并合成了6个新结构螺环吲哚化合物, 并在MDM2高表达的前列腺癌LNCaP细胞株上测定其活性, 结果表明化合物5, 6的半数抑制浓度均低于1μg·mL^-1, 可作为新的抗肿瘤药物先导化合物进一步深入研究. 本研究对以MDM2为靶点的新结构螺环吲哚类抑制剂的开发提供了理论和实验依据.