Synthesis,Biological Activities And Quantitative Structure Activity Relationship Of Rosin Based Diterpenoid Derivatives

Rosin is a kind of renewable resource and rosin acids are the main components of rosin.Rosin acids derivatives have important application in the pharmaceutical and insecticide fields.In this thesis,41 rosin based esters,dihydroabietic amide derivatives,rosin based polyamine derivatives were synthesized from dehydroabietic acid,dihydroabietic acid,maleopimaric acid and acrylopimaric acid through esterification,reduction and amidation.Their structures were characterized by IR,IHNMR,13 C NMR and Single Crystal X-ray Diffraction.Their antifeedanf activities and antitumor activities in vitro were also investigated.Quantitative structure activity relationship(QSAR)of antitumor activities against human lung cancer A549 cells of rosin based diterpeniod derivatives were explored.The antifeedant activities of rosin based diterpenoid derivatives were investigated by dipping lesf disc method.The armyworm and aphid were selected as test insects.The result shows that the rosin based diterpeniod derivatives displayed extensive antifeedant activity against armyworm at the concentration of 0.01 g/mL.The feeding deterrence values of the compound 2k after 24 h,48 h and 72 h were 80%,83.3% and 85.7%,respectively.The deterrency index increased comparing with raw material.Among them,the rosin based polyamine derivatives 4c and 4f exhibited good antifeedant activities against aphids,and the feeding deterrence values were still beyond 90% after 72 h.The antifeedant activity of armyworm mainly affected by the number of amino atoms.The feeding deterrence values of the compound 2r against aphid after 24 h,48 h were 75%,100%,respectively.Dihydroabietic amide derivatives and rosin based polyamine derivatives showed attractant activity against aphid.From the results,it can be concluded that with the introduction of ester group at carbonyl position,increased activity,but with the introduction of acyl and amino groups decreased activity.The antitumor activities in vitro of rosin based diterpeniod derivatives were researched by MTT method.The human lung cancer A549 cells,human gastric carcinoma MKN45 cells,human breast cancer MCF-7 cells,human colon cancer SW1116 cells were selected as test cells.The result shows the rosin based diterpeniod derivatives displayed extensive antitumor activities in vitro against A549 cells,MKN45 cells,MCF-7 cells and SW1116 cells.Among them,the rosin based ester derivatives 2a and 2p exhibited certin antitumor activities in vitro against A549 cells,and their IC50 were 10.78 mg/L and 10.27 mg/L,respectively.The rosin based ester derivatives 2a and 2p showed good antitumor activities in vitro against A549 cells,and their IC50 were 7.27 mg/L and 6.21 mg/L,respectively.The antitumor activity were affected by the chain length of alkyl,anhydride group and hydroxy group.The activity of antitumor increased with the concentration raising.Quantitative structure activity relationship(QSAR)of antifeedant activities of rosin based diterpeniod derivatives were explored.The result shows that the value of R2 and F were 0.3391 and 7.4399.Most of the data were in the middle area,and it can't be quantitative structure-activity relationship.Quantitative structure activity relationship(QSAR)of antitumor activities of rosin based diterpeniod derivatives were explored.The statistical modelings reveal that against A549 tumor cells activity was affected by four descriptors.The four descriptors of the regression coefficients are positive,which present positively correlated with human lung cancer A549 cells.The “XY Shadow / XY Rectangle” belong to the geometrical descriptors,which showed the XY shadow areas of the molecule.The “DPSA-3 Difference in CPSAs” belong to the electrostatic descriptors reflect Charged partial surface area.The “ESP-HA dependent HDCA-1/TMSA” belong to CPSA descriptors,which refiect the hydrogen bonding donor ability of the molecule.The “Avg bond order of a O atom” belong to quantum-chemical descriptors,which reflect the average bond order of oxygen atom.The model was validated by internal check,which showed better stability and good prediative power.