Synthesis And Biological Activity Of Chromanone Skeleton Spliced Trifluoromethyl Spiro Epoxidized Indole Compounds

With the continuous development of science and technology,the incidence of cancer is declining,the pathogenesis is constantly being fully revealed,and specific treatment methods are constantly being updated and developed.However,the treatment of malignant tumors still cannot be cured,and the situation is still bad.Therefore,researchers have developed effective anti-tumor target inhibitors with low side effects that are related to the future of human life and health.The chromone skeleton has good biological activity.The flavonoids substituted at the 2-position,the isoflavones substituted at the 3-position,and similar flavonols have attracted the attention of researchers.The chromone core has become an important pharmacodyna mic segment in drug design.At the same time,the spiro compound has significant biological activity,and the efficient construction of a three-dimensional complex spiro skeleton has aroused great interest.In particular,the spiro ring with multiple stereogenic centers plays an important role in the structure-activity relationship of antifungal and antitumor drugs.Thus,the enrichment of the synthetic repertoire for building these spirocyclic chromanones has always been an active field of high impact in heterocyclic synthetic and medical chemistry.The first part of this thesis is to synthesize trifluoromethyl spiroepoxy indole compounds through the cycloaddition reaction between the trifluoromethylated indole oxide skeleton and the differently substituted chromanone skeleton.After a series of condition screening,the optimal reaction conditions were obtained as follows:at room temperature,CH₂Cl₂was used as the solvent,DABCO was used as the catalyst,and the reaction time was 24 h.A total of 24 trifluoromethyl-spiroepoxyindole-chromanon-e compounds（3a～3x）were synthesized.Inspired by the successful construction of the chromone-oxyindole skeleton,considering that the development of compounds containing this skeleton will be an important heterocyclic compound for the discovery of new active molecules,we have used nitroisoxazole styrene as the raw material,and The ketone-oxyindole synthon C₃was stirred at room temperature for 3 days in the phase transfer catalyst Na₂CO₃,TBAB and CH₂Cl₂solution.8 spirocyclic oxidized indole compounds（5a～5h）of isoxazolchromanone spliced were synthesized.The second part of the work is to use the MTT method to evaluate the anti-tumor activity of the synthesized compounds in vitro.The positive control drug is cisplatin,which is commonly used clinically and has broad-spectrum anti-cancer activity.The cell line is human chronic myeloid leukemia cell line K 562 cell line,and synthetic trifluoromethyl-spiroepoxyindole is taken.Four of the dol-chromanone compounds were subjected to in vitro anti-tumor activity experiments,and the results showed that the compounds 3f、3v and 3w all have a certain degree of inhibitory effect on the proliferation of K 562 cells.