Research On The Total Synthesis Of Diterpene Natural Products Paeoveitol And Fortunolide A

In this paper,we have studied on syntheses of Paeoveitol and Fortunolide A.The content has been divided into two chapter as follow:Chapter 1:studies on the total synthesis of Paeoveitol.Paeoveitol is a pair of new norditerpene,which is isolated from the root of traditional Chinese medicine,namely "Chuan-Chi-Shao".In this section,firstly,we have briefly overviewed the intermediate o-QM,which included the research background,methods for preparation,the construction of natural product skeleton types and application in total synthesis of natural products,which demonstrated the advantages of o-QM intermediate for building the skeleton of natural products such as benzopyrans and benzo-spirones and illustrated the high efficiency of o-QM intermediates in the construction of natural products.Secondly,based on the separation and structure characteristics of Paeoveitol and its analogues.we have designed the intermolecular[4+2]-cycloaddition reaction between Paeoveitol D and o-QM intermediates to efficiently complete the biomimetic synthesis of Paeoveitol.Through the studies on the model substrates,the optimal conditions for intermolecular[4+2]-cycloaddition reactions have been fixed and successfully applied to the total synthesis of the natural product Paeoveitol.Finally,we have understood the reason why only one isomer was afforded in the experiment by a DFT calculations.It has been found that the presence of a crucial intermolecular hydrogen bond and ?-?stacking interaction should be responsible in this case.Chapter 2:studies on the total synthesis of Fortunolide AIn this Chapter,we have described the isolation,framework,bioactivities of Harringtonolide and 27 analogs and Moreover,we have reviewed the three total syntheses of Harringtonolide.In addition,we have highlighted on intruducing the synthesis of Fortunolide A.The cage-like Fortunolides A contains an unusual tropone,a compact 5/6/6 tricyclic ring system,a bridged lactone and a benzylic tertiary hydroxyl group at C10 position and Biologically,Fortunolide A has been found to show a good anti-tumor activity.Based on its structural characteristics,we have designed a palladium-catalyzed intramolecular Heck reaction/CO Insertion/C-H activation tandem reaction to construct the 6/5/6/6 tetracyclic system.In addition,the improved Tiffeneau-Demjanov reaction developed by the Lee's group to construct tropone ring in the final stage of synthesis.However,it was demonstrated that the oxidation of substrate with tropone ring was difficult.We thought the difficulties shown here should be attributed to the.sensitive of tropone and relatedly poor aromaticity compared with benzene ring.Therefore,the synthetic route was redesigned.and the targets product was accomplished with the oxidation of benzene substrate.After screening the conditions,it was found that DDQ as common oxidizer was superior to give the desired product in a high yield.Finally,the expected ring expansion of six-membered ring to seven-membered ring was failed.Although we thought the use of strong bases and generation of weak acids in the reaction probably led to the decomposition of the desired product,obviously,we have to do more in this case.