Studies On Synthesis Of Bioactive Benzofunan Neolignans As Well As Its Vinyl Ether And Glucosidases Derivatives

Dihydrobenzofuran and benzofuran neolignans are widespread in nature, with important biological activity and are potent ingredients of medicinal plants. In order to meet the needs for selecting the substances with biological activities and developing new drugs, this thesis aims at the studies on synthesis, structural modification and biological activity screening of dihydrobenzofuran neolignan compounds and benzofuran neolignan compounds.First, aiming at constructing dihydrobenzofuran skeleton, the synthetic routes were devised; through the following reaction process six benzofuran neolignans compounds have been synthesized. Starting from Vanillin and malonic acid, via Knoevenagel reaction, esterification reaction, Ag2O-catalyzed biomimetic oxidative coupling reaction in three steps, the compounds (10) containing a dihydro- benzofuran skeleton was synthesized. Compound (11) and (12) were synthesized from compound (10) via methylized reaction and DDQ dehydrogenate reaction in two steps. Synthesis of compound (12) not only achieved transformation successfully from dihydrobenzofuran neolignans to benzofuran neolignans, but also offered a new method to synthesize benzofuran construction. On the basis of compounds (12) to further refine the product of the target compounds (1) ~ (6) have been synthesized through the further modification of the compound (12). Compounds (1) and (2) were synthesized via deacetyl reaction of compounds (12); Compound (3) and (4) were synthesized via reduction of compounds (12) with lithium aluminium hydride; Compounds (13) were synthesized via reduction of compounds (12) with H2/Pd-C, further reduction of compound (13) with lithium aluminium hydride yielded compound (5) and (6). The key steps involved the Ag2O-catalyzed biomimetic oxidative coupling of the methyl ferulate form the dihydrobenzofuran skeleton and the DDQ dehydrogenate of the dihydrobenzofuran neolignans form the benzofuran neolignans among the entire synthetic route. Compounds (2), (3), (4) and (5) have been not reported in literatures until now. All of the synthesized compounds have been confirmed by 1H NMR, MS and IR.Second, the synthetic benzofuran neolignans as substrate, of which 4'-OH were replaced by a series of other functional group. First, Benzofuran neolignans were treated with prenyl bromide or trans, trans-farnesyl bromide and anhydrous potassium carbonate in anhydrous acetone at ambient temperature, five benzofurans neolignans-O-prenyl and -O-farnesyl compounds (19) ~ (23) were synthesized. Second,Designed a simple and effective synthetic path to benzofuran neolignans glycosides,which based on researching the synthesis of glycosides. a series of benzofuran neolignans glycosides have been synthesized from glucose by a series synthetic steps including acetylation,bromization,glycosidation,deacetylation reaction. The synthetic procedure of glycosidation was modified by using anhydrous potassium carbonate in anhydrous acetone at room temperature, and the deacetylation using a weak base (ammonia) for hydrolysis reagent, this method has advantages of mild reaction conditions, easy separation of products and high stereospecificticy and yield was also relatively high. In this paper the benzofuran neolignans acetyl-glucosides and glycosides (24) ~ (30) were synthesized. These compounds (19) ~ (30) have been not reported in literatures until now. All of the synthesized compounds have been confirmed by 1H NMR, MS and IR.Third, using suforhodamine B protein staining method, the compounds (10), (11) and (14) ~ (18) were evaluated for potential anticancer cell activity to the BGC-823 (human gastric cancer cell line), U251 (human glia cell tumor) and B16 (mouse melanoma cell lines). The rest illustrated that compounds (10), (11), (14) and (15) showed some activity against BGC-823 cells; compound (10) showed some activity against U251 cells; compounds (16), (17) and (18) showed some activity against B16 cells.