水饱和离子液体中脂肪酶催化萘普生甲酯对映选择性水解  

Enantioselective Hydrolysis of Naproxen Methyl Ester by Lipase in a Water-Saturated Ionic Liquid

作　　者：辛嘉英[1] 赵永杰[2] 石彦国[1] 夏春谷[2] 李树本[2] 

机构地区：[1]哈尔滨商业大学食品与药物工程学院,黑龙江哈尔滨150076 [2]中国科学院兰州化学物理研究所羰基合成与选择氧化国家重点实验室,甘肃兰州730000

出　　处：《催化学报》2005年第2期118-122,共5页

基　　金：国家自然科学基金重点项目 (2 993 3 0 40 ) ;国家重点基础研究发展规划项目 (G19990 2 2 40 6) .

摘　　要：对比研究了水饱和异辛烷和水饱和离子液体 1 正丁基 3甲基咪唑六氟磷酸盐 ([bmim]PF6)中脂肪酶催化萘普生甲酯不对称水解反应 .结果表明 ,由于离子液体 [bmim]PF6同时具有极性和疏水性 ,因而成为萘普生甲酯不对称水解反应的理想介质 .与水饱和异辛烷相比 ,水饱和离子液体不仅明显降低了水解反应的平衡常数 (K) ,增大了对映体比率 (E) ,从而有效提高了水解反应的平衡转化率 (ceq)和产物的对映体过量值 (eep) ,而且由于离子液体对另一产物甲醇的溶解度高 ,还明显地提高了脂肪酶的操作稳定性 .(S)-(+)-2-(6-methoxy-2-naphthyl) propionic acid ( Naproxen) is a nonsteroidal antiinflammatory drug widely used for human connective tissue diseases. The physiological activity of S-form Naproxen is 28-fold that of R-form. In this paper, the lipase-catalyzed selective hydrolysis of Naproxen methyl ester in water-saturated isooctane and water-saturated ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] PF6) was comparatively studied with special attention to the significant differences between the two reaction media in terms of enantiomeric ratio (E) and equilibrium constant (K). It is shown that the polarity and hydrophobicity of [bmim]PF6 made it a more unearthly reaction medium for the hydrolysis of Naproxen methyl ester. Compared with the result of hydrolysis in water-saturated isooctane, the K value for the hydrolysis in water-saturated [bmim]PF6 decreased from 12 to 0.7 and the E value increased from 88 to 356. As a consequence, a higher enantiomeric excess of remaining substrate and enantiomeric excess of product were obtained at a particular conversion, and the enantioselectivity was improved strikingly. The results indicate that [bmim]PF6 is particularly useful as a medium for the enzymatic hydrolysis of Naproxen methyl ester that is difficult to achieve desired conversion and enantiomeric excess in conventional water-saturated organic solvents. The lipase-catalyzed reaction was repeated four times with the recycling of enzyme. The good stability of lipase in [bmim]PF6 was attributed to the higher solubility of methanol in [bmim]PF6 than in isooctane.

关 键 词：离子液体 脂肪酶 萘普生甲酯 对映选择性水解 萘普生 

分 类 号：TQ463[化学工程—制药化工]