Palladium Metalized Porous Organic Polymer Catalyzed Synthesis And Antitumor Activity Of Benzofuran [2,3-b] Pyrazine Compound

The development of simple and efficient organic synthesis reaction to directly construct complex multi-functional group compounds from cheap and easily available raw materials is considered to be an ideal way,which is also one of the research hotspots of organic synthesis.As one of the outstanding C1 sources,isonitriles have been widely employed to construct various nitrogen-containing heterocyclic compounds under the homogeneous metal catalysis.However,there are few reports about the heterogeneous metal-catalyzed organic reaction of isonitriles.In this paper,we have synthesized a palladium nano porous organic phosphine polymer catalyst,and it was successfully applied in the synthesis of the novel benzofuran[2,3-b]pyrazine compounds with antitumor activities from isonitriles and o-halogen phenols.?1?The traditional metal-catalyzed homogeneous reactions suffer from some drabacks such as expensive metal or poor reaction selectivity etc.The metal residue in the products limits the further application of bioactive molecules.Herein,we have synthetized the vinyl-functionalized phosphorus ligands from simple raw materials,then the phosphorus ligands were polymerized into porous organic phosphorus ligand polymers by solvothermal polymerization.Subsequently,metals were loaded on the porous organic phosphorus ligand polymers to get nano-palladium porous bidentate phosphorus ligand polymer catalysts?Pd NPs/POL-xantphos?.?2?Benzofuran-fused N-heterocycles are the dominant structure of drug molecules.There are few methods having been reported for the preparation of benzofuran[2,3-b]pyrazines.And these methods involve pre-functionalization or need complex raw materials.Hence,we reported that the highly selective reaction between o-halogen phenol and isonitrile catalyzed by Pd NPs/POL-xantphos.Benzofuran[2,3-b]pyrazine have been synthesized in one step via this method,and Pd NPs/POL-xantphos could realize catalytic circulation.The catalytic activity of the catalyst do not reduce after 10 times of recycling.A gram reaction for the synthesis of benzofuran[2,3-b]pyrazine compounds was also successfully carried out,which laid the foundation for its industrial application.?3?The in vitro anticancer activity of benzofuran[2,3-b]pyrazine compounds were tested with MTT assay.It was found that compound 3w exhibited good antitumor activities toward T-24 and HeLa cells with IC₅₀ values of 12.5 and 14.7?M,respectively.Compound 3w exhibited better antitumor activity on HeLa cells compared with 5-FU and cisplatin.Then,the anti-tumor mechanism of 3w was studied.The results showed that compound 3w inhibited tubulin polymerization,induced apoptosis,elevated intracellular Ca²⁺release,and increased ROS in T-24 cells.