Regioselective Biomimetic Synthesis Of Oligostilbenes

The chemical synthesis of oligostilbenes were briefly reviewed in this thesis and theoxidative coupling reactions of5-tert-butyl-isorhapontigenin catalyzed by different enzymeswere intensively studied. Natural isorhapontigenin dimer (±)-Gnetulin was firstly synthesizedthrough a series of functional groups transformation of the8-8-coupling products.Additionally, the oxidative coupling reactions of3,5-di-tert-butyl resveratrol under variousenzymatic conditions were also preliminarily investigated. This thesis was divided into thefollowing three parts.1. Chemoselective synthesis of oligostilbenesThe developments on the chemoselective synthesis of oligostilbenes in recent years werebriefly reviewed. The asymmetric synthetic approaches to resveratrol oligomers wereespecially introduced and some innovative and unique synthetic strategies were presented.2. Biomimetic synthesis of several isorhapontigenin oligmersPhosphine ylide23was prepared through five-step reaction starting from benzoic acidmethyl ester19. The basic stilbene skeleton was constructed in Wittig reaction by the reactionof Phosphine ylide with two kinds of tert-butyl substituted benzaldehyde.We studied the coupling reactions of precursor13in the different oxidative conditions,and obtained8-8-coupled intermediates17,33or34, respectively. By modifying thesecoupling dimeric structures with several Lewis acids, we prepared the key intermediate18and increased the yield of18by optimizing the reaction conditions. Finally, natural Gnetulin(9) and unnatural isorhapontigenin dimers36were firstly synthesized in a one-pot reaction.3. Biomimetic synthesis of resveratrol oligomersWe studied the oxidative coupling of coupling precursor1in different conditions byintroducing two tert-butyl groups to resveratrol. The stable structure quinine methide2as asingle product in varied yields was formed either by changing the solvent conditions orenzyme catalyst. Then compound12was afforded by subjecting quinine methide2to aceticacid. Finally, we try to reach the key structures13by the elimination reaction of12underacidic condition, which still led to the stable skeleton2. The followed experiments are stillongoing in our group.In brief, in this paper we studied the enzyme-promoted oxidative coupling of two kindsof coupling precursors under different solvent conditions. The introduction of tert-butylgroups in the coupling precursors obviously improved the regioselectivity of couplingreaction. Finally, we successfully prepared two dimeric isorhapontigenin, Gnetulin (9) and36.The our progress on the regioselective biosynthesis of oligostilbenes is beneficial experiencesfor the future synthesis of this family of natural oligomers.