Studies On The Synthesis And Bioactivity Of Benzodioxane And Prenylated Flavonoids

Benzodioxane（piperonyl and 1,4-benzodioxan）are important organic synthetic drug intermediates,with a wide range of biological activities such as antibacterial,anti-tumor and anti-inflammatory,due to their high efficiency,low toxicity and biodiversity,more and more derivatives containing benzodioxane have been discovered and synthesized in drug molecules.Two active groups of piperonyl and1,4-benzodioxan were introduced on the structure of flavonoids,using the principle of activity superposition.To increase its biological activity,several prenylated flavonoids were synthesized.1、17 kinds of chalcone containing benzodioxane（piperonyl and 1,4-benzodioxane）were synthesized by aldol condensation reaction（1a-1k,5a-5f）,using2-hydroxyacetophenone and benzaldehyde derivatives with different substituents as raw materials.With method of I₂/DMSO oxidation,17 corresponding flavonoids（2a-2k,6a-6f）were obtained by ring-closing reaction.Piperonylic and polymethoxy flavonoid（4）was obtained from the compound（2e）through DMDO oxidation and O-methylation.The total synthesis of four flavonoid natural products（2c,2d,2j,4）were achieved.2、The antiproliferative activities of flavonoids were tested in vitro on a panel of four human cancer cells lines（ASPC-1,HCT116,HEPG2 and SNU5）by CTG assay,The results showed that most piperonyl-flavonoids exhibited potential antiproliferative activitys on tested cancer cells lines.In particular,compound（6f）showed the superior antiproliferative activitys(IC₅₀<4.8μM)than positve control cis-Platin against the three human cancer cell lines（ASPC-1,HCT116,HEPG2）,and showed the best antiproliferative activity on HEPG2 cells(IC₅₀=1.65μM).3、3’-Prenylated chalcone（9,10,13,14）and 5’-Prenylated chalcone（15,16）were synthesized through O-prenylation,intramolecular[1,3]or[1,5]shift reaction with the catalysis of three acid clays,using four chalcones containing benzodioxane as raw materials,and the key step of intramolecular[1,3]or[1,5]shift reaction was discussed.The yield of Montmorillonite K10 and KSF as a catalyst to synthesize prenylated chalcones is higher than that of Flofisil;The 3’-Prenylated chalcones were obtained with the catalysis of Montmorillonite K10.4、Natural occurring 4’-7-dimethoxy-5 hydroxyflavone（17）was through I₂/Py dehydogenation,glycoside hydrolysis and selective methylation,using naringin as the raw material.6-Prenylated flavonoid（19）and 8-Prenylated flavonoid（20）were synthesized from compound（17）,by reaction steps O-prenylation and intramolecular[1,3]or[1,5]shift reaction with the catalysis of three acid clays.6-Prenylated flavonoids can be obtained with the catalysis of Montmorillonite K10 in a high yield,8-Prenylated flavonoids can be obtained with the catalysis of Florisil in a high yield.The structures of all synthesized compounds in this paper have been confirmed by¹H NMR,¹³C NMR and HRMS.