Synthesis Of DDB Analogues

The fruits of Schizandra Chinese have been used as a tonic and astringent drugin traditional Chinese medicine. Its constituents, lignans are antihepatotoxic (liverinjury), anticonvulsive and exhibit antitumor, anti-HIV, and antifungal activities.Most of these lignans have the structural feature of dibenzocyclooctandiene.Dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate(-DDB) and bicyclol exhibit significant antiheptotoxic activity and effectively lowersthe serum-transaminase level. The biphenyl unit of these natural products is crucialfor their pharmacological activities.For the purpose of finding new antihepatotoxic drugs, DDB analogues weresynthesized from the starting material of gallic acid. In this thesis, the synthesis ofDDB analogues was studied by 3 routes: (1) By intra-molecular coupling reactions.(2) By intermolecular Ullmann coupling reactions. (3) By Suzuki unsymmetricalcoupling reactions. In route (1),the reactions were catalyzed by Cu or Pd cannotgive biphenyl product. In route (2), 7 new β-DDB derivatives were synthesized bythis new method. The shortcoming of the reported method by which cannot produceβ-DDB derivatives was overcome by this route. In route (3), biphenyl products weresynthesized by Suzuki reactions. The optimum reaction conditions weren[Pd(OAc)2]/n(bromide)=3%, n(4-methoxyphenylboronic acid)/n(bromide)=2:1 ,K2CO3 as base, acetone-water [V(acetone):V(water)=1:1] as solvent at 70℃ for5h.10 new DDB analogues were prepared in this thesis. All of these newcompounds have biphenyl unit. Their Structures were confirmed by 1NMR spectra.