| The wide variety of oligostilbene with excellent biological activities are mainly synthesized by the direct oxidative coupling reactions of stilbene monomers.However,the traditional oxidative reactions of stilbenes led to the relatively complicated coupling products resulting in the difficult separation and the low isolated yields.Therefore,our group studied the regioselective oxidative coupling reactions through the introduction of bromine as the positioning protecting groups into the resveratrol precursor,and effectively synthesized several natural resveratrol dimers with different skeletons.Based on this,the thesis will continue to investigate the regioselective oxidative coupling reactions of bromoisorhapontigenin under the various oxidative conditions for the synthesis of natural isorhapontigenin dimers with complex structures.Additionally,the oxidative cross-coupling reactions of different bromo-stilbenes were also explored and an expected cross-coupling dimers was successfully prepared,which was the basis for the regioselective synthesis of hetero-stilbene oligomers and ligan-stilbenoids.The thesis was divided into the following four parts:In the first chapter,the distribution in nature and structural features of natural oligostilbenes were introduced,and their artificial synthetic routes in recent years and the related reaction mechanisms were also summarized.The biomimetic synthesis of the oligostilbenes with complex structures through the regioselective oxidative coupling reactions were emphatically reviewed.The application of the oxidative cross-coupling reactions in the biomimetic synthesis of natural lignan-stilbenoid compounds were also briefly introduced.In the second chapter,the Fe Cl3·6H2O-catalyzed oxidative coupling reactions of bromo-isorhapontigenin in different solvent systems including acetone,benzene-acetone,acetone-water and methanol were extensively studied.M8-M10 coupled benzodihydrofuran skeleton 2-16 were successfully obtained from these oxidative reactions.The reductive debromination of dimeric intermediate 2-16 generated the natural product,Bisisorhapontigenin A（2-17）.Then the global acetylation of 2-17 was performed.The BBr3-promoted demethylation and deacetylation in one-pot reaction was followed for the synthesis of natural product Scirpusin B,but failed owing to the unstable benzodihydrofuran structure under acidic conditions.Additionally,oxidative coupling reactions of bromo-isorhapontigenin catalyze by other metallic oxidants were also investigated,which resulted in the complex coupling products.In the third chapter,the horseradish peroxidase（HRP）-catalyzed oxidative coupling reaction of bromo-isorhapontigenin was studied.The effects of different solvent systems including acetone-water,methanol-water,and ethanol-water on the coupling products were explored in detail.The M8-M8 coupling dimeric intermediates were obtained from differentsolvent systems.The Pd-C catalyzed reductive debrominations of these coupling dimers finally synthesized six natural isorhapontigenin dimers（Gnetubainin I,Gnemontanin E,Lehmbachol A,Lehmbachol B,7-O-ethylgnetuhainin I,Gnemontanin F）,respectively.In the fourth chapter,the oxidative cross-coupling reactions between bromo-isorhapontigenin and different brominated phenolic monomers were preliminarily investigated.The cross-coupling reaction of bromo-isorhapontigenin with bromo-resveratrol was firstly explored.Cross-coupling product 4-25 with dihydrobenzofuran structure was finally isolated by adjusting the addition sequence and molar ratios of two precursors.Dimeric intermediate 4-25 was treated with Li Al H4 to remove the bromine protecting group and synthesized the final dimer 4-27.Next,the oxidative cross-coupling reactions of bromo-isorhapontigenin with sinapyl alcohol or bromo-coniferyl alcohol were attempted to prepare some novel cross-coupling products.In view of the different reactive activities of two precursors under the same oxidative conditions,the expected cross-coupling products were not found at present,and this work is still undergoing in our laboratory.We intensively studied the oxidative coupling reactions of bromo-isorhapontigenin under various oxidative conditions and synthesized a dihydrobenzofuran-type isorhapontigenin dimers and six natural oligostilbenes with indane rings with higher yields.We also explored the oxidative cross-coupling reactions of different brominated stilbene precursors,and successfully prepared a cross-coupling product of isorhapontigenin and resveratrol.Finally we preliminarily attempted the oxidative cross-coupling reactions of phenylpropanoids and stilbene to synthesize more natural lignan-stilbenoid compounds,and this work is undergoing in our group. |
