嗜热酯酶对槲皮素的高度区域选择性酰基化反应研究  

Study on Highly Regioselective Acylation Reaction of Quercetin by Thermophilic Esterase

作　　者：马雨婷 王子川 杨梓博 路佳荫 于香雨 姜丽艳[1] MA Yuting;WANG Zichuan;YANG Zibo;LU Jiayin;YU Xiangyu;JIANG Liyan(College of life Science,Jilin University,Changchun 130012,China)

机构地区：[1]吉林大学生命科学学院,吉林长春130012

出　　处：《合成化学》2025年第2期119-125,共7页Chinese Journal of Synthetic Chemistry

基　　金：吉林省自然科学基金资助项目(20230101155JC)。

摘　　要：槲皮素是一种具有显著药理作用和治疗潜力的类黄酮,然而因其较差的生物利用度而使其开发应用受到严重阻碍。脂肪酶能够催化类黄酮发生酰基化反应来改善亲脂性,提高生物活性。采用源自古生菌Archaeoglo-bus fulgidus嗜热酯酶(AFEST)突变体AF-S48I对槲皮素进行酰基化研究,系统考察了在非水相有机介质中嗜热酯酶AF-S48I催化槲皮素酰基化反应的酶活及区域选择性的影响因素。结果表明:酰基供体、反应溶剂、水活度及反应温度对槲皮素的酰基化反应具有不同程度的影响,在槲皮素(0.1 mmol)、乙酸乙烯酯(3.5 mmol)、乙腈20 mL、水活度0.60的最佳催化条件下,60℃反应8 h,AF-S48I酶活性最高(155±3μmol·g^(–1)·h^(–1)),产物转化率可达95%±2%,而且对槲皮素的C—4'位置具有高度区域选择性(>98%)。Quercetin is a flavonoid compound with significant pharmacological effects and therapeutic potential,but its development and application have been seriously hindered due to their poor bioavailability.Lipase can catalyze the acylation of flavonoids to improve their lipophilicity and enhance their biological activity.In this work,enzymatic conversion of quercetin has been performed by thermophilic esterase mutant(AF-S48I)from the archaeon Archaeoglobus fulgidus(AFEST).The factors affecting the enzyme activity and regioselectivity of the acylation of quercetin by AF-S48I in organic media were systematically investigated.As a result,solvent,acyl donor,water activity and reaction temperature can influence the reaction in different degrees.Under the optimum catalytic conditions of quercetin(0.1 mmol),vinyl acetate(3.5 mmol),acetonitrile(20 mL)and water activity of 0.60,60℃for 8 h,the activity of AF-S48I was the highest at 155±3μmol·g^(–1)·h^(–1),the conversion of the product was up to 95%±2%,and the AF-S48I exhibited specificity towards the C-4'position of quercetin(>98%).

关 键 词：槲皮素 嗜热酯酶 高度区域选择性 酰基化反应 酶活 

分 类 号：O629.8[理学—有机化学]