Design,Synthesis Of Flavonoid Ethers With Allene Fragments And Their Biological Activity Study

Objective:Flavonoids are polyphenolic compounds that are ubiquitously found in plants.They are among the most investigated phytochemicals due to their pharmacological and therapeutic activities.However,most flavonoids were not developed as clinical drugs because of poor bioavailability(less than 5%).Methods:Some novel chemistry methodologies intermediate products which developed by us were also involved in the synthesis of flavonoid ethers to diversify quickly.Herein,we report a method to improve the bioavailability of flavonoids,in which a C(sp~2)-O bond is formed between the ethyl-2,3-butadienoate allenes and the hydroxyl group of flavonoids.Gratifyingly,we found that the starting materials with the OH groups at position of 3'and 4'gave the products with 1,3-dioxolane,instead of desired through a simple electrophilic reaction.Results:The method demonstrate a highly stereoselective and regio-selective alkenylation.36 flavonoid ethers derivatives were synthesized without the use of protective groups.Anti-cancer activity assay results showed that compounds 4b,4c,4e,5e and 6b exhibited better inhibitory activity against different cancer cell lines in vitro than that of their substrates,respectively.(21 flavonoid derivatives)Conclusion:Preliminary structure-activity relationship studies indicated that,in most of cancer cell lines evaluated,the 7-position substituent was essential for cytotoxicity.These results of the research will facilitate the preparation or late-stage modification of complex flavonoids for applications in research and drug discovery.Expected that,an efficient and convenient cobalt-promoted annulation reaction hasbeenestablishedforthesynthesisofbiologicallyrelevant phosphaisoquinolin-1-ones,whichrepresentsthefirstexampleofa transition-metal-promoted C-H/N-H functionalization of aryl phophinamides with allenes.Throughthisstrategy,threedifferenttypesofnovel phosphaisoquinolin-1-one derivatives can be readily prepared in good yields.This new strategy exhibited several advantages,including easily accessible starting materials,good functional group tolerance,and excellent reactivity.