Preparation Of Resveratrol O-Glycosides And Biomimetic Synthesis Of Oxyresveratrol Dimers

Resveratrol O-glycosides are a type of natural stilbene products,which are widely distributed in nature.These compounds have good biological and pharmacological activities as well as high medicinal value.In recent years,it has attracted widespread attention of biologists and chemists.This kind of compounds was obtained much more from the extraction and separation than chemical synthesis with low yield and poor regioselectivity and stereoselectivity.For the purpose of bioactivity research and drug development and application,this paper intended to conduct a preliminary exploration on the synthesis of resveratrol O-glycoside monomers.Oxyresveratrol is also a kind of natural polyphenol compounds,which has similar biological activity with resveratrol,and has a high prospect for biomedical applications.At present,the synthesis of such compounds was mainly restricted in the monomer research stage,and there was only one report on the synthesis of oxyresveratrol dimmers with very low yield?6%?.Herin this paper intended to explore the biomimetic synthesis of oxyresveratrol dimmers in order to find a concise synthetic strategy for this class of oligomers.This thesis mainly includes the following four chapters:In the first chapter,the O-glycosidation methods,the synthesis of resveratrol O-glycoside monomers,and the research progress of oxyresveratrol in recent years were briefly reviewed.The project background and research content in this topic were also introduced.In the second chapter,the direct glycosylation reaction of resveratrol and bromo-resveratrol with acetyl bromide-?-D-glucose under sonication conditions was first attempted.Due to the complexity of the reaction system,the target product was not isolated and identified.Through reviewing the literature and analyzing the reasons,we found that the three phenolic hydroxyl groups of resveratrol monomers have obviously different reactive regioselectivity.So we changed the synthetic strategy and tried the Lev and TBS selective protection of 4?-position phenolic hydroxyl group of resveratrol monomer followed the 3-O-glycosylation reaction.However,the glycosidation reaction of 4?-O-Lev-resveratrol under the sonication reaction conditions gave rise to complex products and the target 3-O-glycoside was not obtained.The glycosylation reaction of 4?-O-TBS-resveratrol catalyzed by Ag₂CO₃ or BF₃·Et₂O also failed owing to the difficulty in the separation and identification of complex products formed.The glycosylation reactions of 4?-O-TBS-bromo-resveratrol were conducted under 9 kinds of catalytic systems.Eventually,only 4?-O-?-D-bromo-resveratrol glycoside was synthesized in the Ag₂CO₃/quinoline or Ag₂CO₃/quinoline-CH₃CN catalytic system due to the migration of TBS protecting group to 3-hydroxyl group.Then we adopted the glycosylation of the 3,5-dihydroxybenzaldehyde substituted benzaldehyde followed by the Wittig reaction to construct the stilbene skeleton.The expected 3-O-?-D-resveratrol glycoside derivative was finally prepared by using this synthetic strategy.In the third chapter,the oxyresveratrol monomer was synthesized by multistep reaction with higher yield.The oxidative coupling reaction of oxyresveratrol catalyzed by enzyme and ferric chloride was tried respectively.But the couling dimer was not separated and identified because of the complex product system.The reason may be that the higher activity of 2?-hydroxyl group of oxyresveratrol led to the poor regioselective controll in the coupling reaction.In view of this,2'-phenolic hydroxyl group was firstly protected by methyl ether,then protected monomer was used to carry out oxidative coupling reaction under the HRP or FeCl₃ catalytic conditons.A M₈-M₅-coupled dimer and M₈-M₁₀-coupled dimer with moderate yield were successfully synthesized.In the fourth chapter,the synthetic progress of the phenanthrene compounds was reviewed,and the photocyclization reaction of stilbenes was preliminarily explored.First,six stilbene monomers were synthesized through the multi-step reactions,and four phenanthrene derivatives were successfully synthesized under the conditions of a 300W high pressure mercury lamp.In conclusion,we have synthesized 4?-O-?-D-bromo-resveratrol glycoside,3-O-?-D-resveratrol glycoside,two oxyresveratrol dimers and four phenanthrene derivatives.The strategies for the efficient synthesis of resveratrol glycosides and oxyresveratrol dimers with higher yield and better regioselectivity have been developed,which would be applicable for the future synthesis C-glycosides,O-glycosides and other oxyresveratrol dimers.