Study On Biomimetic Oxidative Cross-coupling Reactions Of Stilbene Monomers

In nature,there are a large number of stilbene oligomers,most of which are polymerized from various stilbene monomers,usually forming dimers such as dihydrobenzofuran and indane polymer or multimer.They have diverse biological activities and have important medicinal and economic values.Most of the stilbene oligomers found so far are extracted from plants,some are self-coupled structures polymerized by the same stilbene units,and some are made of different stilbene cross-coupled structure formed by unit-like units.If the extraction method is only used to get the oligostilbenes,the yield was very low,and the sepraration and purification would be difficult and costly.Therefore,it is desirable to obtain stilbene oligomers with various structures through artificial synthesis.Most of the reports on the chemical or biomimetic synthesis of oligostilbenes are self-coupling of stilbenes,while the synthesis of cross-coupling oligomeric products are rarely reported.Our research team introduced bromine as the protective group to stilbene monomers to improve the regioselective control in their oxidative coupling reactions and has synthesized a variety of self-coupled stilbene dimers.Therefore,based on our previous results,this paper will study the oxidative cross-coupling reactions of different stilbene monomers under the enzyme-promoted or metal oxidant-catalyzed oxidative conditions.This thesis will be divided into the following three parts for discussion:In the first part,the oligomers of stilbene self-coupling extracted directly from many plant communities in recent years were reviewed,and the natural products with stilbene monomer self-polymerization structure were obtained by chemical synthesis or biomimetic synthesis.In addition,the natural heteropolymer structures from different stilbene monomers and the stilbene-neolignan compounds formed by the polymerization of stilbene and phenylpropanoid were briefly introduced.Based on the above research results of biomimetic self-coupling polymers,herein our research group intend to study the oxidative cross-coupling reactions of stilbene monomers.In the second part,the oxidative cross-coupling reaction of resveratrol and bromo-isorhapontigenin in acetone/water system catalyzed by HRP-H2O2 was studied.Firstly,two coupling precursors were synthesized,and their individual oxidative coupling reactions under enzyme conditions were investigated to determine the compatible precursors for oxidative cross-coupling reactions.Then the equivalent ratio and addition sequence of the two monomers and catalyst in the cross-coupling reaction were studied through parallel experiments.The effects of different feeding methods,addition sequence and reaction time on the yield of M8-M5 cross-coupled product were discussed.The optimized oxidative cross-coupling reaction conditions was finally determined as followed:resveratrol was added dropwise in batches,and the addition time was within 40 minutes.Then the bromine protecting group was removed from the cross-coupling dimer to successfully synthesize the natural product?±?-Gnetuhainin Q.A cross-coupling reaction of resveratrol and bromo-isorhapontigenin in Fe Cl3-acetone system was studied in the third part.Mostly similar to the experimental methods in the second chapter,only the addition sequence of two prcursors was changed.We found the ideal M8-M10cross-coupled dimeric product with higher yield was obtained when two coupling precursors was added at the same time.Then the debromination reaction of cross-coupling dimer gave rise to a derivative of natural?±?-Scirpusin A.The subsequent direct removal of the methyl group from this dimeric derivative in BBr3/DCM system failed due to its insolubility in DCM.After the global acetylation of the dimer,the ont-pot reaction including demethylation and deaceylation under BBr3/DCM resulted in complex products and did not isolate the expected natural?±?-Scirpusin A.The oxidative cross-coupling reactions of resveratrol and bromo-isorhapontigenin catalyzed by enzyme and metal oxidants were studied and two different cross-coupling heterodimer-M₈-M₅-coupled and M₈-M₁₀-coupled product were synthesized.In order to improve the yield of cross-coupling dimeric prodcut and reduce the formation of self-coupling products,the cross-coupling reaction conditions were continuously adjusted and optimized.We expected that the biomimetic cross-coupling reaction conditions can be applied to the future synthesis of natural stilbene heterooligomers with different structures.