抗病毒药物阿比朵尔的6位结构修饰-应用化学专业毕业论文.docxVIP

抗病毒药物阿比朵尔的6位结构修饰Modification 抗病毒药物阿比朵尔的6位结构修饰 Modification of Antiviral Arbid01 on 6．Position Abstract 6-bromo-4一((dimethylamino)methyl)一5一hydroxy一1一methyl一2-((phenylthio)methyl)-1H-in dole一3-carboxylic acid ethyl ester hydrochloride，also named arbidol，is an important non—nucleoside class of antiviral drug．Referring to the literature method，ethyl acetoacetate and benzoquinone were chosed as an starting material to synthesize arbidol via amination, Nenitzescu cylization,O-acylation reaction,bromination and Suzuki coupling reaction．In this study，6-position of Arbidol was structural modified and the synthetic conditions were optimized． The synthetic conditions were optimized such as the O．acylation reaction．bromination reaction,and Suzuki coupling reaction．The Suzuki coupling reaction between intermediate 4 and arylboronic acids was investigated．The results showed that the Suzuki coupling reaction occured on the benzyl bromide preferentially． Fifteen new target compounds(6a-60)were obtained，which has the best antiviral compound 5 as the starting material，and introduced different kinds of aryl groups to its 6-position by the Suzuki coupling reaction．Their structures were characterized by 1H NMR， 13C NMR and HRMS．The substrate scope was investigated with-CH3，．OCH3 as electron-donating functional group and-F，-C1 as electron-withdrawing group．While when there is—OH，-COCH3，-Br group in the structure，it is difficult to get the target molecule． Key Words：Arbidol；Suzuki Coupling Reaction；Anti-influenza Virus Activity； arylboronic acids —I】 万方数据 大连理工大学硕士学位论文目 大连理工大学硕士学位论文 目 录 摘 要 I Abstract ．II 引 言 1 1 文献综述 ．2 1．1流感病毒 ．．2 1．1．1流感病毒概述 ．2 1．1．2流感的预防 ．．3 1．1．3流感的治疗 一3 1．2新型抗流感病毒药物阿比朵尔 6 1．2．1 阿比朵尔的研究进展 ．6 1．2．2阿比朵尔的合成路线 ．6 1．2．3阿比朵尔的临床研究 ．9 1．3 Suzuki偶联反应 lO 1．3．1 Suzuki偶联反应机理 10 1．3．2影响Suzuki偶联反应的因素 ．12 1．3．3苄基卤的Suzuki偶联反应 ．16 1．4阿比朵尔的结构修饰 一l 6 1．5立题依据 l 8 2 6．取代芳基．5．乙酰氧基．2．(2．甲氧基苄基)．1．甲基．1厚吲哚．3一羧酸乙酯(6a一60) 的合成 ．19 2．1实验仪器、试剂及溶剂的纯化 ．19 2．1．1 实验仪器 19 2．1．2实验试剂 20 2．1．3溶剂的纯