2007 年 6 月 Journal of Chemical Engineering of Chinese Universities June 2007 文章编号:1003-9015 (2007)03-0481-07含离子液体介质中脂肪酶高效催化对羟基苯甘氨酸甲酯不对称氨解吴虹, 娄文勇, 宗敏华(华南理工大学轻工与食品学院, 广东广州 510640)摘要:利用离子液体C6MIm·BF4 (20%,v/v)/叔丁醇混合介质中脂肪酶Novozym 435催化对羟基苯甘氨酸甲酯不对称氨解反应,高效地制备了对映体纯D-对羟基苯甘氨酸酰胺。
该反应的最适氨源为氨基甲酸铵,其较佳浓度为120~160mmol⋅L−1;最适水活度、反应温度、pH值、对羟基苯甘氨酸甲酯浓度分别为0.55~0.75、35~40℃、7.5~8.0和40 mmol⋅L−1。
在上述条件下,反应初速度和对映体选择比分别为5.88 mmol⋅L−1⋅h−1和83 (E值),反应6 h,产率为47.6%,产物e.e.值为92.9%。
与有机溶剂叔丁醇相比,脂肪酶Novozym 435在C6MIm·BF4 (20%,v/v)/叔丁醇混合溶剂中的操作稳定性显著提高,反应7批次后,仍能维持90%以上的催化活性,而在叔丁醇反应介质中,仅能维持41%的催化活性。
关键词:脂肪酶;不对称氨解;对羟基苯甘氨酸甲酯;离子液体中图分类号:TQ925.6;TQ225.41 文献标识码:AAsymmetric Ammonolysis of D,L-p-hydroxyphenylglycine Methyl Ester Catalyzed by Lipase in an Ionic-Liquid-Containing SystemWU Hong, LOU Wen-yong, ZONG Min-hua(College of Light Industry and Food Sciences, South China University of Technology,Guangzhou 510640, China)Abstract: Using lipase Novozym 435 as mediator and the ionic liquid (IL), C6MIm·BF4 (20%, v/v)/ terrt-butanol co-solvent mixture, as reaction medium, the enantiomerically pure D-p-hydroxyphenylglycine amide was prepared via asymmetric ammonolysis of D,L-p-hydroxyphenylglycine methyl ester (D,L-HPGME). Ammonium carbamate was found to be the best ammonia donor for the reaction and its favorable concentration is 120~160 mmol⋅L−1. The optimal water activity, reaction temperature, pH value and concentration of D,L-HPGME are 0.55~0.75, 35~40℃, 7.5~8.0and 40 mmol⋅L−1, respectively. Under above mentioned conditions, the initial reaction rate and enantiomeric ratio (E) of the reaction are 5.88 mmol⋅L−1⋅h−1 and 83. After reaction time of 6 h, the yield and the product e.e. are 47.6% and 92.9%, respectively. Comparing with using terrt-butanol as reaction medium, using C6MIm·BF4 (20%, v/v)/ tert-butanol co-solvent mixture as reaction medium, the operating stability of Novozym 435 increases remarkably and its enzymatic activity retains above 90% of its original value after being repeatedly used for 7 batches, while with tert-butanol as medium, only 41% original activity of Novozym 435 can be retained.Key words: lipase; asymmetric ammonolysis; D,L-p-hydroxyphenylglycine methyl ester; ionic liquid1前言D-对羟基苯甘氨酸及其衍生物是合成阿莫西林、头孢羟氨苄、头孢哌酮、头孢罗奇、头孢羟胺唑等β-内酰胺抗生素药物必不可少的侧链。