Asymmetric Synthesis And Activity Evaluation Of Spiropyrrolidinylbisoxindoles

The 3,3'-pyrrolo oxindole structure is ubiquitous in many active natural products and is a core skeleton whose compound has biological activity.The anti-tumor activity of these compounds is significant,mainly in the inhibition of cell mitosis,induction of DNA cleavage,induction of tumor cell apoptosis,inhibition of microtubule polymerization,etc.,has been the focus of scientists.During the master's degree,I mainly made asymmetric synthesis and activity evaluation of a double spiro oxime compound containing different substituted 3,3'-pyrrolo oxindole structures.Divided into the following three parts:?1?Asymmetric synthesis of bisoxindoles containing nitroisoxazole.The Michael/Cyclization reaction was carried out under the catalysis of quinine with3-isothiocyanato oxindoles with 5-isatylidenyl-isoxazoles.The reaction conditions were optimized,and 30 spiropyrrolidinylbisoxindoles compounds containing nitroisoxazole were synthesized.The melting point was measured for all the compounds,and the ee value was determined by HPLC.The structure of the compound was confirmed by¹H NMR,¹³C NMR and MS-ESI.?2?Asymmetricsynthesisofbisoxindolescontainingacetate.The Michael/Cyclization reaction was carried out under the catalysis of quinine with an acetate-condensed 3-eneoxide and 3-isothiocyanate.The reaction conditions were optimized,and 13 spiropyrrolidinylbisoxindoles compounds containing acetate were synthesized.The melting point was measured for all the compounds,and the ee value was determined by HPLC.The structure of the compound was confirmed by¹H NMR,¹³C NMR and MS-ESI.?3?Using the MTT method,the clinically used anticancer drug cisplatin was used as a positive control,and 18 compounds were extracted from the 43 target compounds synthesized?3aa,3ab,3ad,3af,3ah,3aj,3ak,3al,3an,3aq,3at,3''a,3''b,3''d,3''i,3''l,3''m,3''n?conduct preliminary evaluation of in vitro antitumor activity,and examine its effect Cellular inhibition of human non-small cell lung cancer cell line A549,human chronic myelogenous leukemia cell line K562 and human prostate cancer cell line PC-3.The results showed that the compounds 3ah,3aq and 3at had good inhibitory activity on K562 proliferation in vitro.According to the results,further structural modification and activity studies are needed.