新型苯并二氢呋喃合二酮酸类化合物的合成及其与整合酶分子对接研究

以阿魏酸甲酯为原料，通过氧化偶联构建2-芳基苯并二氢呋喃骨架，再经傅克酰基化和酯缩合反应依次制得(E)-3-［2-(4-羟基-3-甲氧基-5-乙酰基)苯基-3-甲氧羰基-7-甲氧基-2,3-二氢苯［b］并呋喃-5-基］丙烯酸甲酯（3）和(E)-3-［2-(4-羟基-3-甲氧基-5-甲氧羰基乙酰基)苯基-3-甲氧羰基-7-甲氧基-2,3二氢苯并［b］呋喃-5-基］丙烯酸甲酯（4）； 4经水解反应合成3-【2-羟基-3-甲氧基-5-｛5-［2-（甲氧基羰基）乙烯基］-7-甲氧基-3-甲氧羰基-2,3-二氢苯并［b］呋喃-2-｝基】苯基-3-氧丙酸（5），化合物3~5未见文献报道，其结构经¹H NMR， ¹³C NMR和MS(ESI)表征。采用分子对接软件Autodock vina对化合物2~5与HIV-1整合酶核心部位高度同源的PFV IN（PDB: 3L2V）进行对接，计算结果显示该类化合物能与整合酶形成稳定的复合物，具有1,3-二酮基团的化合物3， 4和5能与整合酶中金属离子产生螯合作用，其中化合物5的结合作用最强。

Synthesis of Novel Dihydrobenzofuran Compounds andMolecular Docking of Them with Diketoacid

2-Aryl dihydrobenzob]furan skeleton was constructed from methyl ferulate through oxidative coupling reaction.Friedel-Crafts acetylation and ester condensation were applied to synthesize (E)methyl 3-2-(4-hydroxy-3-methoxy-5-acetyl)phenyl-3-methoxcarbonyl-7-methoxy-2,3-dihydrobenzob]furan-5-yl] arcylate(3) and (E)methyl 3-2-(4-hydroxy-3-methoxy-5-methoxcarbonacetyl)phenyl-3-methoxcarbonyl-7-methoxy-2,3-dihydrobenzob]furan-5-yl]acrylate(4).The compound 4 was hydrolyzed to afford 3-(2-hydroxy-3-methoxy-5-(5-(2-(methoxcarbonyl)vinyl)-7-methoxy-3-methoxcarbonyl-2,3-dihydrobenzob]furan-2-)yl)phenyl-3-ox-propanoic acid(5).Among them, 3~5 were new compounds.The structures were characterized by 1H NMR, 13C NMR and MS(ESI).Autodock vina was applied for molecular docking of compound 2~5 toward prototype foamy virus(PFV) integrase(IN)(PDB: 3L2V), a highly homologous protein of HIV-1 IN.The results showed that the stable complexes could be formed between these compounds and IN.In particular, compound 3~5 with 1,3-diketo moiety can chelate with metal ions in the IN, and affinity of compound 5 is strongest.