Biomimetic Synthesis Of Natural Dihydroaryltetralin Lignans

Lignans, a class of secondary plant metabolites, are oligomers produced by oxidativepolymerization of phenylpropanoid monomers such as cinnamic acid and its hydroxylderivertives: ferulic acid, coffeic acid and sinapic acid. Enormous structural complexity ofnatural occurring lignans led to their extensive biological activities. Dihydroaryltetralin typelignans attracted considerable attentions of chemists due to the discovery and application ofpodophyllotoxin and its analogues with prominent anticancer activities, and became a veryhot research topic in lignan chemistry in recent years. The synthesis of them in vitro becameincreasingly neccessary owing to their limited contents in nature. There are two types ofsynthetic strategies for lignans: chemical and biomimetic synthesis. The oxidative couplingdimerization of phenolic phenylpropanoids are conventional methods to construct the basicskeletons of natural lignans. In this thesis, total biosynthesis of several types ofdihydroaryltetralin lignans were developed by using the oxidative coupling reaction of ferulicacid derivatives as the key steps. The following three parts were included:Chapter1：Structural classification and progress on the synthesis of lignans.Starting from the classification and biological activities of lignans, recent syntheticadvances of lignans are primarily introduced. Some new reactions, new reagents and newstrategies applied in the synthesis of lignans were also briefly described.Chapter2: Biomimetic synthesis of dihydroaryltetralin lignans.Some commonly synthetic routes of aryltetralin lignans were firstly introduced. In thisthesis, The regioselective oxidative coupling reaction of ferulic acid derivatives bearingposition protecting groups catalyzed by different metallic oxidants constructed the basic8-8-coupled lignan skeletons. Then diverse dihydroaryltetralin intermediates were preparedby a series of subsequent structural modification isomeric arrangements of coupling products.The final debutylation of them afforded several unnatural dihydroaryltetralin lignans andnatural (±)-8-8-aryl-diFA. All the related mechanisms of coupling reactions and isomerizationwere also discussed in detail, which will offer a beneficial references for the future syntheticinvestigation of this kind of lignans.Chapter3: Synthesis of natural lignanamide (±)-Canabisin DBased on the our regioselective biomimetic synthesis of dihydroaryltetralin lignans,natural lignanamide (±)-Canabisin D was synthesized by the condensation of(±)-8-8-aryl-diFA with tyramine hydrochloride in high yield. The synthesis of other naturaldihydroaryltetralin lignans through the similar structural transformation of (±)-8-8-aryl-diFAwere ongoing in our team.