A systematic analysis of the variables that control a highly stereoselective resolution of racemic non-steroidal antiinflammatory drugs using immobilized lipase from Candida cylindracea
A systematic analysis of the variables that control a highly stereoselective resolution of racemic non-steroidal antiinflammatory drugs using immobilized lipase from Candida cylindracea
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DOI：
10.1016/1381-1169(95)00021-6
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发表时间：
1995-05
影响因子：
--
通讯作者：
J. Moreno;JoséV. Sinisterra
中科院分区：
文献类型：
--
作者：
J. Moreno;JoséV. Sinisterra
研究了一种酶法生产S（+）2-芳基丙酸的方法。该方法包括由共价固定化Candida cylindracea脂肪酶催化的外消旋乙酯的立体选择性水解。反应的性能和产率作为关键反应参数如温度、底物浓度、pH、离子强度和搅拌速度的函数进行评价。搅拌速度的增加，底物浓度的降低和pH = 7.0有利于酯的水解。研究了酯的烷基链和醇残基对反应的影响。乙酯和丁酯是进行水解的最令人感兴趣的酯。使用固定化衍生物可以实现外消旋体的高对映选择性水解（产生S（+）异构体; ee ≥ 95%）。几种固定化衍生物产生的S（+）2-芳基丙酸的不同产率与底物的结构参数有关，这是通过分子力学研究的，并支持物的亲水性和亲脂性的底物之间的关系。活性位点的模型提出了有关使用的底物和反应产率。固定化的衍生物在三个循环中重复使用，并显示出80%的残留活性后，336小时的操作时间。
An enzymatic method for the production of S( + ) 2-arylpropionic acids has been developed. The process consists of the stereoselective hydrolysis of the racemic ethyl esters catalyzed by covalent immobilized Candida cylindracea lipase. The performance and yield of the reaction were evaluated as a function of the critical reaction parameters such as temperature, substrate concentration, pH, ionic strength and stirring speed. An increase in the stirring speed, a diminution of the substrate concentration and pH = 7.0 favors the hydrolysis of esters. The influence of the alkyl chain and the alcoholic residue of the ester have been studied. The ethyl and butyl esters are the most interesting esters for carrying out hydrolysis. High enantioselective hydrolysis of the racemates (yielding S( + ) isomer; ee ≥ 95%) can be achieved using the immobilized derivatives. The different yields of S( + ) 2-arylpropionic acids produced with the several immobilized derivatives are related to structural parameters of the substrate, which were studied by molecular mechanics, and to the relation between the hydrophilicity of the supports and the lipophilicity of the substrates. A model of the active site is proposed in relation to substrates used and reaction yields. The immobilized derivatives were re-used in three cycles and showed an 80% residual activity after 336 h of operating time.