Total Synthesis And Biological Activity Evaluation Of Coryaurone A And Its Derivatives,Study On Synthesis Of Bavachinone A

This thesis aimed at total synthesis and biological activity evaluation of Coryaurone A and its derivatives,and study on synthesis of Bavachinone A,the detail contents could be divided into the following three parts:Chapter 1:Research Progress of Aurones CompoundsThe first part summarized the classification of flavonoids,the research progress and synthesis example as anticancer drugs.And brief introduction of the isolation,structural characterization,biological activity of the Aurones.Chapter 2:Total Synthesis and Biological Activity Evaluation of Coryaurone A and its Derivatives.The natural product Coryaurone A is isolated from Psoralea corylifolia L.It is Aurone compound with dihydrofuran structure.Because Coryaurone A has good biological activity and novel structure,Several of these compounds exhibited moderate inhibitory activity toward Staphylococcus mutans-derived Srt A and significant stimulation of SIRT1 activity,moreover,the report of its total synthesis has not been seen.So we decided to synthesis of Coryaurone A,and derivatize its skeleton to study its further anti-cancer activity.We Used commercial available 6-hydroxy-2H-benzofuran-3-one as the starting material,in the concrete synthesis process,using Lindlar hydrogenation,Claisen rearrangement,Shi Asymmetric Epoxidation,Aldol reactions,we successfully obtained target natural product and its derivative compounds in 7-8 steps,the total yield is 34.12%-45.92%..Then,We have studied the anti-cancer,anti-inflammatory and anti-fungal activities of these compounds.Our preliminary screening of these compounds showed CA₁and CA₂have good inhibitory activity against leukemia HL-60 and colon cancer SW480,and the inhibition rates were 89.99%/62.90%and 54.97%/89.11%respectively.Due to its good inhibitory activity against leukemia HL-60 and colon cancer SW480,the IC₅₀values were further determined for all compounds.The result showed that compound CA₁₂had an excellent inhibitory activity on leukemia HL-60(IC₅₀values 3.92μM),while CA₁,CA₅,CA₉,CA₁₈,CA₁₉have showed excellent inhibitory activity on colon cancer SW480(IC₅₀values 13.44μM,10.92μM,7.68μM,9.19μM,8.24μM).We also tested the anti-inflammatory activity of these compound,the compounds CA₁₁and CA₁₂(with IC₅₀values of 1.04μM and 1.86μM,respectively)showed excellent anti-inflammatory activity.The anti-fungal activity test is to conduct a preliminary screening of crop harmful fungi,such as Botrytis cinerea,Fusarium grainii and Tomato leaf mildew etc,at the concentration of 100μg/m L.Unfortunately,none of these compounds had inhibitory activity.Chapter 3:The Study on Synthesis of Bavachinone AThe natural product Bavachinone A was isolated from Psoralea corylifolia L by Jongheon Shin’s research group in 2015,and there has been no report on its total synthesis.After careful review of the literatures,we used 2,4-dihydroxyacetophenone as the starting material,using methyl protection,isopentenyl bromide substitution,para Claisen rearrangement,MOM protection and esterification reactions,we successfully obtained the moiety 6 in 5 steps.We are now trying to use asymmetric Michael addition/decarboxylation reaction to construct chiral center,and the synthesis of this natural product is still in progress in our lab.