Study On Synthesis And Inhibitory Activities Of Nr2B Ca²⁺-flux Of Isoindoline Derivatives,and Study On Chemical Constituents Of Marsdenia Tenacissima And Calotropis Gigantea

The whole thesis consists of four parts:(1) Study on synthesis of isoindolin-1-imine derivatives via one-pot reaction and their inhibitory activities of NR2B Ca2+-flux;(2) Study on synthesis of2-substituted-3-(2-oxoalkyl)isoindolin-1-one derivatives via one-pot reaction;(3) Study on C21steroidal glycosides from the Stems of Marsdenia tenacissima;(4) Study on the isolation, structural determination and cytotoxicities of cardenolides from the bark of Calotropis gigantea.Isoindolin-1-imine derivatives are an important class of isoindole scaffold, which exhibit typical pharmacological activities as NR2B-selective NMDA (N-Methyl-D-aspartate) receptor antagonists, and the thrombin receptor (PAR-1) inhibitors. In an effort to explore new method for synthesis of isoindolin-1-imine derivatives, a novel one-pot method for the synthesis of isoindolin-1-imine derivatives has been developed via a simple three-component condensation of2-cyanobenzaldhyde, ammonium acetate, and4-hyroxycoumarin derivatives or1,3-dicarbonyl compounds, or4-hydroxyquinolin-2(1H)-one in ethanol under reflux condition for20-60min with excellent yields. Moreover, a new, simple, efficient procedure for the preparation of3-(2-substituted-3-iminoisoindolin-1-yl)-2-hydroxy-4H-chromen-4-one analogs is decribed in this thesis via a three-component condensation of2-cyanobenzaldehyde, primary amine and4-hydroxycoumarin derivatives in dry dichloromethane without catalyst at room temperature. The condensation reactions are proceeded smoothly and quickly to afford products in excellent yields. The inhibitory activities of NR2B Ca2+-flux of synthesized isoindolin-1-imine analogs have been evaluated via the fluorescence measurement of free concentrations of intracellular calcium of L(tk-) cells expressing NRla/NR2B receptors. The results showed that all tested isoindolin-1-imine derivatives exhibited potent inhibitory activity of Ca2+-flux in cells.An efficient one-pot procedure for the synthesis of2-substituted-3-(2-oxoalkyl)isoindolin-l-one analogs has been developed from phthalaldehydic acid, primary amine, and ketone in aqueous solution under reflux condition in the presence of VB1. Various substrates can be applied to this procedure with operational simplicity, good yields, short reaction time, and environmental friendly conditions.Marsdenia tenacissima (Roxb.) Wight et Arn., is known as a famous traditional Chinese medicine, which is widely used in the treatment of cancer, and other diseases. From ethanolic extract of stem of Marsdenia tenacissima,20compounds have been isolated, including3new compounds and17known ones, and their structures have been elucidated via NMR spectroscopic identification and LC-MS analysis.Calotropis species are known as a source of biological active substances, in particular it is one of a good source of cardenolides. From the90%ethanolic extract of the bark of Calotropis gigantea (C. gigantea), three new cardenolides and eleven known ones have been isolated, and their structures have been elucidated via NMR spectroscopic identification and LC-MS analysis. The inhibitory activities of all isolated compounds have been evaluated against non-small cell lung carcinoma (A549) and human cervix epithelial adenocarcinoma cell line (HeLa), and several cardenolides exhibit strong potent cytotoxicities.