The Studies On The Synthetic Methods Of Bioactive Benzofuran Neolignan And 8-5' Neolignan Compounds

Benzofuran neolignans and 8-5' neolignans are widespread in nature, exhibiting a broad range of biological activities and are potent ingredients of many medicine plants. Benzofuran neolignans include 2-phenyl benzofuran neolignans and its dihydro, tetrahydro, hexhydro derivatives. In order to meet the needs for selecting the substances with biological activities and developing new drugs, this thesis aims at the studies on the synthesis of dihydrobenzofuran neolignan compounds, benzofuran neolignan compounds and 8-5' neolignan componds.1,Starting from vaniline and malonic acid, dihydrobenzofuran compound (13) was synthesized via Knoevenagel reaction, esterification reaction and Ag2O-cataly -zed biomimetic oxidative coupling reaction in three steps. (1) ~ (3) were obtained through methylation, DDQ dehydrogenation and LiAlH4 reduction form compound (13). Three dihydrobenzofuran compounds (4) ~ (6) were obtained through modification of compound (13). Compound (5) was synthesized via the right amount of lithium aluminium hydride reductive reaction of compound (13). Compound (13) reacted with 4-bromo-2-methyl-2-butene to give O-prenylated dihydrobenzofuran compound (6). Meanwhile, Starting from p-hydroxybenzaldehyde under the same condition we got compound (17), followed by reacted with 4-bromo-2-methyl-2- butene to produce O-prenylated dihydrobenzofuran (7). The key step was the biomimetic oxidative coupling reaction, whose mechanism was discussed in this chapter.Seven dihydrobenzofuran and benzofuran compounds (1) ~ (7) were synthesiz- ed. Among them, novel compounds (2),(3),(5),(6),(7) had not yet been reported. All of these synthesized compounds have been confirmed by MS, IR, 1H NMR and13C NMR.2,Dihydrobenzofuran compound (13) reacted with different base to give three different ring-opening compounds (9) ~ (11). Compound (12) was synthesized via dihydrobenzofuran compound (17) under potassium carbonate in THF. Compound (18) was synthesized via dihydrobenzofuran compound (13) which reacted with 4-bromo-2-methyl-2-butane. Compounds (8) ~ (12) and (18) belong to 8-5' neolignan compounds. The mechanism of formation of ring-opening of dihydrobenzofuran compound was discussed at last. Novel compounds (9) ~ (12) and (18) had not yet been reported. All of these synthesized compounds have been confirmed by MS, IR, 1H NMR and 13C NMR.3,The bioactivity screening test of some compounds were developed. The results of showed that compound (2) was determained to have moderate drug toxicity based on human breast cancer cells MDA-MB-231 and glia cancer cell U251. Using HCPT and VINCRISTIN as positive control, IC50 values 1.18μg/ml,0.81μg/ml respectively at the concentration of 10μg/ml. At the concentration of 61μg/ml, compound (8) and (11) showed inhibitory activities against PPI(I type serine / threonine specific protein phosphatase), their IC50 value 60.45μg/ml and 55.65μg/ml respectively. The bioactivity screening test of other compounds wree still in carrying on.