Synthesis Of Diphenyl Derivates

The fruits of Schizandra Chinese have been used as a tonic and astringent drug in traditional Chinese medicine. Its constituents, lignans are antihepatotoxic (liver injury), 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 (α-DDB) and bicyclol exhibit significant antiheptotoxic activities and effectively lower the serum-transaminase level. The biphenyl unit of these natural products is crucial for their pharmacological activities.In this thesis, the synthesis routes ofα-DDB andβ-DDB were optimized. During the synthesis ofα-DDB, the key intermediate ofα-DDB, methyl 2-bromo -3, 4- dimethylenedioxy-5-methoxybenzoate, was synthesized in higher yield by bromination of methyl 3,4-dihydroxy-5-methoxybenzoate with NBS before cyclizing with CH2I2 in DMF. During the synthesis ofβ-DDB, the key intermediate ofβ-DDB, methyl 2-bromo-3,4-dimethylenedioxy-5-methoxybenzoate, was synthesized in higher yield by three steps: cyclization with CH2I2 of methyl gallate, bromination with NBS, and then methylation. The optimized routes have some merits, such as higher yield, mild condition and easy workup.Theγ-DDB analogue was synthesized by a new method—"lactone concept": the biaryl coupling was performed intramolecularly in the presence of PdCl₂(PPh₃)₂, after prefixation of two aromatic moieties as ester type compound by esterification. Two new asymmetric biaryl lactones compounds were synthesized by the same method. Opening one of lactone afforded an asymmetric biphenyl derivative. All of the final compounds had biphenyl unit. Their structures were confirmed by 1H NMR spectra.