Studies On Synthesis Of A New Dihydrobenzofuran Neolignans

Dihydrobenzofuran neolignans,kinds of natural secondary metabolites formed by the oxidative coupling of phenylpropanoid units?C₆-C₃?,widely distributed in plants with a variety of biological activities such as anti-tumor,anti-oxidation,anti-inflammatory,liver propection,antiplatelets aggre-gation activity.For various types of substitutions that can occur on the dihydrobenzofuran ring to make this class neolignans structurally novel with multiple functional groups and chiral centers.These biological and chemical reports make dihydrobenzofuran neolignans attractive targets for chemical synthesis or modification.In this thesis,we focused on total synthesis of the dihydrobenzofuran neolignans Quiquesetinerviusins A and its derivatives.This thesis includes the following three parts:Part one is the summery.We reviewed the research status of lignans,including its definition,classification,extraction,isolation methods,biosynthetic pathways and biological activities.Then the synthesis of benzofuran and dihydrobenzofuran neolignansweresummarized.Next,weproposedatotalsynthesisof dihydrobenzofuran neolignans Quiquesetinerviusins A and its derivatives routes basd on the existing synthetic routes and the current research status.The second part introduced the first total synthesis of dihydrobenzofuran neolignans Quiquesetinerviusins A and its derivatives.Firstly,MOM-protected p-hydroxybenzoic acid ligand was synthesized by p-hydroxybenzoic acid as raw material.Then the dihydrobenzofuran skeleton was constructed via Knoevenagel condensation and oxidative coupling with vanillin and monoethyl malonate.Afterward,DIBAL-H is used to reduce the THP protected dihydrobenzofuran to diol compound which condensation and deprotected with the acid ligand to obtain the target product Quiquesetinerviusins A.Finally,activated manganese dioxide selectively oxidizes the allylic alcohols of the key intermediate diols to aldehydes,which was esterified with acid ligand and removed the protecting groups to obtain the desired compounds.Part three,discussing the important rections and mechanisms were discussed.The efficient conditions was achieved by contrast esperiments,such as catalyst type,molar ratio,reaction temperature and time and other factors.In addition,we found that Ag₂O catalyzed free radical oxidative coupling reaction can produce dihydrobenzofuran and biphenyl neolignans.The dihydrobenzofuran skeleton can be ring-open to form 8-5'lignans under alkaline conditions,which provides new ideas and methods for synthesis of different types of lignans in the future.