酪氨酸酶催化反应及其应用研究-有机化学专业论文.docx

摘要苄氧基苯酚在酪氨酸酶和芳香胺作用下得到了相同的三取代胺的主产物3-1，4-苯 摘要 苄氧基苯酚在酪氨酸酶和芳香胺作用下得到了相同的三取代胺的主产物3-1，4-苯 基苯酚得到了两个吩嗪环主产物3-4和3—5。 3．采用固定化酶在有机溶剂中催化了对位取代苯酚和芳香胺的反应，得到相 同类型的三个胺取代产物4-1、4-2、4-3，取代基从醌环上脱落。基于该反应机理， 设计了酪氨酸酶的三个前药模型化合物并进行了体外模型实验，即以酪氨酸酶的 底物苯酚和邻氨基苯酚作为药物布洛芬和5一氟脲嘧啶的载体，经酪氨酸酶和亲核 试剂的作用，实现药物的释放。结果表明，前药模型化合物4．5和4-8可以释放药 物，化合物4．12还在研究中。 4．对合成的化合物进行了乙酰胆碱酯酶的抑制活性测定，结果表明：3-4 (IC50=103．7 ttM)和3—5(IC50=20．6 IaM)具有较好的抑制活性：根据化合物3-4和 3—5对乙酰胆碱酯酶的抑制动力学行为表明它们是竞争型抑制剂。 5．在无溶剂下，研究了Ⅱ一糜蛋白酶催化N．保护的氨基酸葡萄糖酯的合成， 结果表明，底物比、加酶量、加水量、pH值和反应时间对反应有影响，其中加水 量影响较大，反应产物正在研究中。 本论文主要化合物附图如下 。，7丫丫o＼。 XN／≮／≮N，7 驭 Ar=oq)CH3-c014 联||| 双‰ 3．1 。 驭：砹 ：取0仑J一弼叫‰ 4—2：A卢。‘ClC6H4 4-5 3-5 ‘l。Ar=C‘HE Ar=o-0C|『3吨6H4 mb趣一毋《。bp O 口 卜NH c．％～iU净o 、 螂 4-12 II 中山大学博士学位论文 中山大学博士学位论文 徐迪019101024 Abstract Topic：Wyrosinase catalytic reactions and applications Author：Xu Di Supervisor：Prof．Gu Lian—Quan，Prof．Ma Lin Majoring：Organic chemistry The market for biological catalysis is continuously growing，especially in the pharnlaceutical，environment and food industries．But the use of enzymes in aqueous reaction media limited their applications in the scope of industrial．The snccess of such application has led to interest in new media such as organic solvent，supercritical fluids， reverse micelle and solvent·free．In this article，some recent developments in enzymatic catalysis in non-aqueous media will be reviewed and enzymatic solvent·-free synthesis will also be described， It is well known that tyrosinase is the key enzyme of melanin biosynthesis，which catalyzes two distinct reactions involving molecular oxygen：the hydroxylation of monophenols to o—diphenols and the oxidation of both to o—quinones．which are electrophilic and known with undergoing a variety of noncnzymatic reactions such as oxidation—MichaeI addition reaction with amino or thiol groups， In this article，oil the basis of oxidation—Michael addition reaction catalyzed by tyrosinase，the oxidation reactions of hydroxypyridines，three prodrug models of tyrosinase and the reactions in solvent—flee sys