Organic Synthesis And Its Application: Stereoselective Synthesis Of Spiro-oxindoles And Implementation Of Molecular Probes For Anti-Migration

In this paper,stereoselective synthesis of spiro[pyrrolidin-3,3'-oxindoles] was studied and cell migration sites with their related target proteins were preliminarily labeled by the synthesis of two molecular probes and showed by their biological activities.These two studies based on organic synthesis and its applications have important guiding significance for the design,preparation and pharmacological research of anti-tumor drugs.In the aspect of stereoselective synthesis of spiro[pyrrolidin-3,3'-oxindoles],the stereo configuration of spiral products constructed by Mannich reaction was studied,which was influenced by the kinds of metal catalysts,chiral amine ligands,solvents and temperature.A highly stereoselective one-pot intramolecular Mannich reaction using L-2-oxotryptaphan methyl ester and aromatic aldehydes as substrates was developed as follows: ZnCl2-2,2'-diaminobiphenyl complex as catalyst system,dioxane/H2O(v1:v2=9:1)mixture as solvent,K2CO3 as base,1:3 as the ratio of L-2-oxotryptaphan methyl ester and benzaldehyde and 50? as the reaction temperature.The dominant product which configuration is(3R,2'S)was obtained with a high stereoselectivities of 91%.In the research of molecular probes for cell migration inhibitors,two kinds of molecular probes with fluorescein or biotin as reporter group,lysine as linker group,and bisazole peptidomimetics cell migration inhibitor as recognition group have been studied.And the structure was confirmed by mass spectrometry.Cell co-incubation assays showed that these molecular probes could effectively label the receptor proteins of migration inhibitors on tumor cells.Co-incubation with cell lysate and electrophoresis experiments showed that the molecular weight of the target protein bound by the molecular probe was about 250 kDa.The molecular probes synthesized in this paper provide an effective material means for determining the target protein and mechanism of action of cell migration inhibitors.