Study Towards The Total Synthesis Of Bi-magnolignan And Spiroaspertrione A

Oxidative coupling is a method to construct carbon-carbon bonds and carbon-heteroatom bonds.Different from classical transition metal-catalyzed coupling,oxidative coupling does not require pre-functionalization of the substrate.Generally,the reaction can be initiated by adding appropriate oxidants,which is green and efficient.In this thesis,oxidative coupling was used as the key reaction to explore its application in the synthesis of two natural products.In the first part,the oxidative coupling reactions of enols and phenols are introduced.Secondly,the source of bi-magnolignan and its inhibitory activity on tumor cells,as well as the synthesis of dibenzofuran compounds were introduced.Finally,the source of spiroaspertrione A,its activity against Methicillin-resistant Staphylococcus aureus（MRSA）and its synthesis were reviewed.In the second part,the synthesis of bi-magnolignan was studied.Starting from4-allylanisole and 1,2,4-trimethoxybenzene,two fragments of boronic acid and bromobenzene were synthesized in an efficient strategy by functionalization of the raw materials and condition optimization.The two fragments were coupled by Suzuki coupling,followed by demethylation and intramolecular dehydration condensation to construct dibenzofuran monomer.Finally,through condition screening,the first total synthesis of natural product bi-magnolignan was completed with a coupling yield of 56%under the condition of ferric trichloride（Fe Cl₃）as oxidizing agent and m-chloroperbenzoic acid（m-CPBA）as oxygenating agent.In the third part,based on the research of our group,we continue to study the synthesis of spiroaspertrione A.Firstly,the eastern fragment and two western fragments were synthesized,and the two fragments were coupled through Michael addition to obtain key precursors.However,the critical enol oxidative coupling（EOC）reactions did not produce the expected product.In the subsequent work,the author changed the synthesis strategy and continued to explore the synthesis of spiroaspertrione A by taking intermolecular Diels-Alder reaction as the key step.At present,a certain amount of dienophile has been prepared,and the synthesis of diene and subsequent work are in progress.