Asymmetric Biosynthesis Of Dihydroaryltetralin Lignans

Lignans possess complex structures and a broad range of biological activities. Manychemists were devoted to the synthesis of natural lignans, which generally involved chemicalor biomimetic strategy. Radical phenol coupling of two phenylpropanoid precursors is themost concise approach to the construction of lignan skeletons. In this thesis, the regioslectiveand steroselective biomimetic synthesis of several dihydroaryltetralin lignans were developedby using oxidative coupling reaction of phenylpropanoids as the key steps. The followingthree parts were included:Chapter1：Progress on the biomimetic synthesis of natural lignansThe recent development on the biomimetic synthesis of lignans was reviewed accordingto the structural classification of lignans. The different reaction conditions and relatedcoupling mechanisms were briefly introduced.Chapter2: Regio-and stereo-selective oxidative coupling reactions of phenylpropanoidsThe synthetic routes to the aryldihydronaphthalene lignans starting from differentphenylpropanoid precursors were firstly outlined. The tert-butyl protecting group wasintroduced in ferulic acid ester via the Friedel-Crafts reaction to improve the regioselectivityof the oxidative coupling reaction. And the introduction of chiral auxiliaries into the aboveprotected precursor through the condensation reaction would achieve the stereoselectivecontrol of the coupling process. Two diastereoisomeric aryldihydronaphthalene couplingproducts were obtained from the oxidative coupling reaction of protected phenylpropanoidscatalyze by FeCl3oxidant. Regio-and stereo-selective control of oxidative coupling ofphenylpropanoid was successfully achieved. Finally, the tert-butyl positional protectinggroups and amide chiral auxiliaries in the coupling products were removed by theretro-Friedel-Crafts reaction and the further hydrolysis to synthesize two chiral8-8-aryl-diFA.Chapter3: Total asymmetric biosynthesis of8-8-aryl-diFA.The biomimetic synthesis of aryl dihydronaphthalene lignans by using different oxidantswere reviewed. Ferulic acid derivatives protected with tert-butyl group was oxidized bypotassium ferricyanide to construct a basic lignan skeleton, which was followed by thedebutylation reaction to remove the protecting groups. Then the amide chiral auxiliaries wereintroduced to this intermidate and the further intramolecular cyclization promoted by Lewisacid formed aryl dihydronaphthalene lignan. Final hydrolysis would completed the synthesisof chiral8-8-aryl-diFA.