摘要
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,^(13)C 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。
2-Aryl dihydrobenzo [ b ] furan skeleton was constructed from methyl ferulate through oxida- tive 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-dihydrobenzo [ b ] furan-5-yl ] arcylate （ 3 ） and （ E ） methyl 3- [ 2- （ 4-hydroxy-3 -methoxy-5 -methoxcarbonacetyl ） phen- yl-3-methoxcarbonyl-7-methoxy-2,3-dihydrobenzo [ b ] 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-methox- carbonyl-2,3-dihydrobenzo [ b ] furan-2- ） yl） phenyl-3-ox-propanoic acid （ 5 ）. Among them, 3 ~ 5 were new compounds. The structures were characterized by I H NMR, 13C NMR and MS （ESI）. Autodock vina was applied for molecular docking of compound 2 ~ 5 toward prototype foamy virus （PFV） inte- grase（IN） （PDB： 3L2V）, a highly homologous protein of HIV-1 IN. The results showed that the sta- ble 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.
出处
《合成化学》
CAS
CSCD
2017年第4期303-307,312,共6页
Chinese Journal of Synthetic Chemistry
基金
新疆维吾尔自治区高校科研计划重点项目(XJEDU2016I031)
新疆医科大学研究生创新创业项目(CXCY097)
