Studies On The Synthesis Of Bioactive Benzofuran Neolignans And New Glycoconjugates

The benzofurans exhibit widely significant biological activities because of theirunique structure. Limited natural sources can not meet the needs for selectingsubstances with biological activities and developing new drugs. And total synthetic orsemi-synthetic method is an effective way to generate benzofurans. Sometimes,benzofuran molecule itself is not always the best medicinal ingredients. We could getmore useful benzofuran structural analogues on the basis of the structure modificationand transformation of lead compounds. In this thesis, the synthesis of benzofuranneolignans and new glycoconjugates were carried out.1、The natural dihydrobenzofuran neolignans1(licarin A) was synthesized fromisoeugenol through biomimetic oxidative coupling. Compound2(2-(3-methoxy-4-hydroxyphenyl)-3-methoxy carbonyl-5-methoxy carbonyl vinyl-7-methoxy–benzofuran) was synthesized from vanillin through Knoevenagel reaction,esterification, biomimetic oxidative coupling, acetylized and DDQ dehydrogenatereaction.2、Starting from glucose, galactose, maltose and lactose, a series of azideacetylated sugar were synthesised, such as azide acetyl glucose, azide acetyl galactose,azide acetyl maltose and azide acetyl lactose, through acetylized bromide and azidereaction. Compound1or2was treated with propargyl bromide solution andanhydrous potassium carbonate in anhydrous acetone, to effect nucleophilicsubstitution reaction and produced terminal alkyne compound19or28. The Cu(I)catalyzed azide-alkyne1,3-dipolar cycloaddition to form a stable1,4-disubstituted-1,2,3-triazole. Then, a series of new type of benzofuran neolignans glycoconjugateswere achieved via deacetylation with sodium methoxide in anhydrous methanol. Thisclick reaction has good efficiency, high purity and high yield.3、The synthesized compounds were evaluated for biological activity against fourhuman cancer cell lines by the standard MTT method. According to the bioactiveresearch, compound10has an inhibitory effect on human gastric cancer cellline(BGC-823); Compound14has an inhibitory effect on human gastric cancer cellline (BGC-823) and human glioma cells (U251); Compound17has selective toxicityto human gastric cancer cell line (BGC-823) and leukemia cells (HL-60).4、Among the fourteen synthesised benzofurans, three are natural product(1、6、12). And another one newly8-5’ neolignans(13) and twelve newly benzofuran neolignans glycoconjugates were synthesised(20-27、29-32). Their structures wereconfirmed by~1H NMR, IR and MS techniques.