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[1]马燕,杨震炯,丁雁,等.Novozym 435催化酮洛芬酯化拆分研究[J].南京工业大学学报(自然科学版),2015,37(06):54-60.[doi:10.3969/j.issn.1671-7627.2015.06.011]
 MA Yan,YANG Zhenjiong,DING Yan,et al.Kinetic resoulution of ketoprofen using Novozym 435[J].Journal of NANJING TECH UNIVERSITY(NATURAL SCIENCE EDITION),2015,37(06):54-60.[doi:10.3969/j.issn.1671-7627.2015.06.011]
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Novozym 435催化酮洛芬酯化拆分研究()
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《南京工业大学学报(自然科学版)》[ISSN:1671-7627/CN:32-1670/N]

卷:
37
期数:
2015年06期
页码:
54-60
栏目:
出版日期:
2015-11-20

文章信息/Info

Title:
Kinetic resoulution of ketoprofen using Novozym 435
文章编号:
1671-7627(2015)06-0054-07
作者:
马燕1杨震炯2丁雁1黄和1胡燚1
1.南京工业大学 生物与制药工程学院 材料化学工程国家重点实验室,江苏 南京 210009; 2.永康市质量监督检测中心,浙江 永康 321300
Author(s):
MA Yan1YANG Zhenjiong2DING Yan1HUANG He1HU Yi1
1.State Key Laboratory of Materials-Oriented Chemical Engineering,College of Biotechnology and Pharmaceutical Engineering,Nanjing Tech University,Nanjing 210009,China; 2.Quality Supervision and Inspection Center of Yongkang,Yongkang 321300,China
关键词:
酮洛芬 Novozym 435 化学修饰 添加剂
Keywords:
ketprofen Novozym 435 chemical modification additive
分类号:
TQ033
DOI:
10.3969/j.issn.1671-7627.2015.06.011
文献标志码:
A
摘要:
通过工艺优化确定Novozym 435催化酮洛芬酯化拆分的适宜条件为:酰基受体正丙醇与反应介质异辛烷体积比为1:9、酮洛芬质量浓度20 mg/mL、反应温度30 ℃、转速200 r/min,24 h后反应的转化率和产物对映体过量值(eep)分别为58.0%和78.2%。研究表明:丁二酸酐和顺丁烯二酸酐修饰的Novozym 435对正丙醇的耐受性获得显著提升,正丙醇在反应体系中与异辛烷的体积比可分别达到3:7和2:8,同时底物酮洛芬浓度可分别提高到40和80 mg/mL。而且,添加剂的加入能进一步改善酶的催化性能,反应20 h后,丁二酸酐修饰的Novozym 435在以β-环糊精为添加剂时,转化率及eep值为48.6%和81.2%; 经顺丁烯二酸酐修饰的Novozym 435在以PEG为添加剂时的转化率和eep值为48.9%和80.1%。
Abstract:
The optimal conditions of the esterification of ketoprofen by Novozym 435 were deterimined as follows:n-propanol as the acyl acceptor,isooctane as the reaction medium and the ratio of 1:9,the concentration of ketoprofen of 20 mg/mL,temperature of 30 ℃,and rotate speed of 200 r/min.After reaction of 24 h,the conversion ratio and the eep value were 58.0% and 78.2%,respectively.Results showed that n-propanol tolerance of Novozym 435 modified by succinic anhydride and maleic anhydride could be improved,the volume ratios of n-propanol to isooctane increased to 3:7 and 2:8,respectively. Besides,the concentrations of ketoprofen reached up to 40 and 80 mg/mL.Moreover,the additives could further improve the catalytic properties of lipase.The conversion ratio and the eep value of Novozym 435 modified by succinic anhydride were 48.6% and 81.2% using β-cyclodextrin as the additive; the conversion and eep value of Novozym 435 modified by maleic anhydride were 48.9% and 80.1% when using PEG as the additive.

参考文献/References:

[1] Zhang Y-Y,Liu J-H.Kinetic study of enantioselective hydrolysis of(R,S)-ketoprofen ethyl ester using immobilized T.laibacchii lipase [J].Biochemical Engineering Journal,2011,54(1):40-46.
[2] Kantor T G.Ketoprofen:a review of its pharmacologic and clinical properties [J].Pharmacotherapy:The Journal of Human Pharmacology and Drug Therapy,1986,6(3):93-102.
[3] Díaz-reval M A I,Ventura-martínez R,D Ciga-campos M,et al.Evidence for a central mechanism of action of S-(+)-ketoprofen [J].European journal of pharmacology,2004,483(2):241-248.
[4] Ossipov M,Jerussi T,Ren K,et al.Differential effects of spinal(R)-ketoprofen and(S)-ketoprofen against signs of neuropathic pain and tonic nociception:evidence for a novel mechanism of action of(R)-ketoprofen against tactile allodynia [J].Pain,2000,87(2):193-199.
[5] Gotor-Fernández,Brieva R,Gotor V.Lipases:useful biocatalysts for the preparation of pharmaceuticals [J].Journal of Molecular Catalysis B:Enzymatic,2006,40(3):111-120.
[6] Patel R N.Biocatalysis:synthesis of key intermediates for development of pharmaceuticals [J].Acs Catalysis,2011,1(9):1056-1074.
[7] Fischer T,Pietruszka J.Key building blocks via enzyme-mediated synthesis [J].Topics in Current Chemistry.2010,297:1-43.
[8] Park J H,Choi W J,Chul Huh E,et al.Production of optically active ketoprofen by direct enzymatic esterification [J].Journal of Bioscience and Bioengineering,1999,87(4):545-547.
[9] D’Antona N,Lombardi P,Nicolosi G,et al.Large scale preparation of enantiopure S-ketoprofen by biocatalysed kinetic resolution [J].Process Biochemistry,2002,38(3):373-377.
[10] Ong A,Kamaruddin A,Bhatia S,et al.Performance of free Candida antarctica lipase B in the enantioselective esterification
   of(R)-ketoprofen [J].Enzyme and Microbial Technology,2006,39(4):924-929.
[11] Rodrigues R C,Berenguer Murcia Á,Fernandez Lafuente R.Coupling chemical modification and immobilization to improve the catalytic performance of enzymes [J].Advanced Synthesis & Catalysis,2011,353(13):2216-2238.
[12] Yin C,Zhang C,Gao M.Enzyme-catalyzed synthesis of vitamin E succinate using a chemically modified Novozym-435 [J].Chinese Journal of Chemical Engineering,2011,19(1):135-139.
[13] Ghanem A,Schurig V.Peracetylated β-cyclodextrin as additive in enzymatic reactions:enhanced reaction rate and enantiomeric ratio in lipase-catalyzed transesterifications in organic solvents [J].Tetrahedron:Asymmetry,2001,12(19):2761-2766.
[14] 熊亚红,苏健鸿,刘小平.修饰脂肪酶催化水解反应的动力学和热力学研究 [J].分子催化,2010,24(5):435-442.
[15] Chen C S,Fujimoto Y,Girdaukas G,et al.Quantitative analyses of biochemical kinetic resolutions of enantiomers [J].Journal of the American Chemical Society,1982,104(25):7294-7299.
[16] Martins J F,de Sampaio T C,de Carvalho I B,et al.Lipase catalyzed esterification of glycidol in nonaqueous solvents:solvent effects on enzymatic activity [J].Biotechnology and Bioengineering,1994,44(1):119-124.
[17] Romano A,Gandolfi R,Molinari F,et al.Esterification of phenylacetic and 2-phenylpropionic acids by mycelium-bound carboxylesterases [J].Enzyme and Microbial Technology,2005,36(4):432-438.
[18] Lee D,Choi Y K,Kim M J.Enhancing the enantioselectivity of lipase in transesterification by substrate matching:an enzyme memory based approach [J].Organic Letters,2000,2(16):2553-2555.
[19] Kovac A,Scheib H,Pleiss J,et al.Molecular basis of lipase stereoselectivity [J].European Journal of Lipid Science and Technology,2000,102(1):61-77.
[20] Shintre M S,Ghadge R S,Sawant S B.Kinetics of esterification of lauric acid with fatty alcohols by lipase:effect of fatty alcohol [J].Journal of Chemical Technology and Biotechnology,2002,77(10):1114-1121.
[21] 唐良华.脂肪酶的生产及其在布洛芬手性拆分中的应用基础研究 [D].杭州:浙江大学,2007.
[22] Dong H P,Wang Y J,Zheng Y G.Enantioselective hydrolysis of diethyl 3-hydroxyglutarate to ethyl(S)-3-hydroxyglutarate by immobilized Candida antarctica lipase B [J].Journal of Molecular Catalysis B:Enzymatic,2010,66(1):90-94.
[23] Phillips R S.Temperature modulation of the stereochemistry of enzymatic catalysis:prospects for exploitation [J].Trends in Biotechnology,1996,14(1):13-16.
[24] Xiong J,Wu J,Xu G,et al.Kinetic study of lipase catalyzed asymmetric transesterification of mandelonitrile in solvent-free system [J].Chemical Engineering Journal,2008,138(1):258-263.
  
[25] Jiang X,Hu Y,Jiang L,et al.Synthesis of vitamin E succinate from Candida rugosa lipase in organic medium [J].Chemical Research in Chinese Universities,2013,29(2):223-226.
[26] Díaz-Rodríguez A,Davis B G.Chemical modification in the creation of novel biocatalysts [J].Current Opinion in Chemical Biology,2011,15(2):211-219.
[27] Szab A,Kotorm N M,Laczk I,et al.Improved stability and catalytic
   activity of chemically modified papain in aqueous organic solvents [J].Process Biochemistry,2009,44(2):199-204.
[28] Uyqnik A,Sen N,Yilmza M.Improvement of catalytic activity of lipase from Candida rugosa via sol-gel encapsulation in the presence of calix(aza)crown [J].Bioresource Technology,2011,102(6):4313-4318.

备注/Memo

备注/Memo:
收稿日期:2014-05-22
基金项目:国家杰出青年科学基金(21225626); 国家高技术研究发展计划(863计划)(2011AA02A209); 江苏高校优势学科建设工程
作者简介:马燕(1989—),女,江苏南通人,硕士,主要研究方向为生物催化; 胡燚(联系人),副教授,E-mail:huyi@njtech.edu.cn.
引用本文:马燕,杨震炯,丁雁,等.Novozym 435催化酮洛芬酯化拆分研究[J].南京工业大学学报:自然科学版,2015,37(6):54-60..
更新日期/Last Update: 2015-11-20