Studies On The Synthesis Of Bioactive Stilbenes And New Stilbene Glycoconjugates

Stilbene compounds are a class of natural products widely found in nature. Thesecompounds have taken extensive attention due to their outstanding biologicalactivities and pharmacological properties such as anti-inflammatory, antioxidation,platelet antiaggregation, heart protection and anticarcinogenic effects. Because ofnew drag targets have updated constantly, the compounds of medicinal chemistryprogress quickly to form new areas of the stilbene compounds, a class of promisingcompounds. However, their content in plants is low and difficult to extract. Previousresearch has proved that the synthrtic stilbenes have identical physiological actionwith that obtained from the natural source. Nowadays, most of synthetic methods havethe high cost of raw materials, harsh reaction conditions, complicayed operation andother shortcomings. In order to meet the biological activity of research and drugdevelopment needs, search for a facile and highly stereoselective synthetic method forpreparation of stilbenes, this thesis aims at the studies on total synthesis and structuralmodification of stilbene compounds and their new type of glycoconjugate.1. Four stilbene derivatives1-4were synthesized in reaction steps includingmethylation, NaBH₄-I₂reduction, bromization, Arbuzov rearrangement, MOMOhydroxyl protection and Wittig-Horner reaction respectively using3,4,5-trihydroxy-benzoic acid （gallic acid） as the starting material. Target compounds are made up ofthe aromatic A ring by the3,4,5-dimethoxy group as substituent, aromatic B ring bythe methoxy and hydroxy as substituent.2. Studies show that Mannich base of pterostilbene have good prevention andtreatment effect on cancer, cardiovascular disease, inflammation and other diseases,which biological activity obviously more than resveratrol and pterostilbene. Four newpterostilbene Mannich base derivatives5-8were synthesized in Mannich reactionusing pterostilbene and pterostilbene derivatives, secondary amine, formaldehyde asthe material.3.1,2,3-Triazole-linked stilbene glycoconjugates20-35, which have been notreported in literatures until now, were synthesized by using stilbene2,4for materialby click chemistry reaction for the firse time. Acetyl glucose azide, acetyl galactoseazide, acetyl maltose azide, acetyl lactose azide as glycosyl azide, using Cu（I） ascatalyst, the1,3-dipolar cycloaddition reaction was taken with stilbene terminalalkynes under the mild reaction conditions of dichloromethane/water system. Thedeacelation reaction was carried out in methanol/sodium methoxide system. This synthesis method were better than other methods with the mild reaction conditions,simple post-processing, high stereoselectivity, and the relatively higher productionrate. The glycoconjugates can enhance the target activity of drug, water-solublility,biocompatibility, and make its have better biological activity.4. This thesis synthesized twenty-six stilbene derivatives, pterostilbeneMannich base derivatives, stilbene glycoconjugates. Among the twenty-two are newcompounds. The structures of the synthesized compounds have been confirmed by1HNMR, MS and IR.