| The latest version of the "World Cancer Report" forecasts that global cancer cases will show rapid growth from 2012’s 14 million annual increase to 19 million in 2025 to 2035 will reach 24 million people.The report also shows that China added 3.07 million cancer patients and cause about 2.20 million deaths,accounting for 21.9%and 26.8%of the global total,respectively.Resveratrol(trans-resveratrol)is a three-stilbene compounds,widely found in plants such as peanuts,grass inlay,grapes and the like.Studies have indicated that it has anti-oxidation,anti-cancer,lowering blood pressure,preventing osteoporosis effect.It has attracted the attention of domestic and foreign researcher by its unique efficacy a,P-unsaturated carbonyl structural unit(Michael acceptor)exists in the molecular structure of many natural products and pharmaceutical entity.Michael acceptor molecule can react with the nucleophilic groups of certain biological macromolecules in Michael addition reaction,through the reaction it can regulate cell signal pathways,generate anti-inflammatory,anti-tumor and anti-viral,and other pharmacological activity.In recent years,Transformation of natural products by adding Michael acceptor structure gains more and more popularity in drug design.In this thesis,we design a synthesis method of resveratrol with satisfactory yield.Then we optimization the route as a method of resveratrol derivatives synthesis.And we ues Michael acceptor as a carrier for resveratrol structural modification.Finally,were synthesized nine intermediates and four final derivate,of which 4 compounds has not been reported in the literature.MS and hydrogen spectrum have confirmed the structure of all the target compounds.We discussed the optimization of synthetic route of the nucleus compounds,hoping to make the nucleus derivatives yields as high as possible in order to do more work regarding the derivatization of the compounds.Using MTT method to measure the biological activity,we measured the IC50 value of four target compounds in HepG2 cells and MCF-7 breast cancer cells,finding that the inhibition activity of III on the HepG2 cells is twice of the RES,and IV showed good inhibition on MCF-7 cells,of which the IC50 value is 212.7μM.Preliminary structure-activity relationship studies indicated that substitute at 2 amino of aβ-unsaturated carbonyl amide III can effectively enhance the inhibitory activity of HepG2 cells.As for MCF-7 cells,the activity of resveratrol series derivatives are weak,IV has slightly stronger activity. |
