Resolution of rac‐ketoprofen esters by enzymatic reactions in organic media
Resolution of rac‐ketoprofen esters by enzymatic reactions in organic media
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DOI：
10.1002/chir.530050508
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发表时间：
1993
期刊：
影响因子：
2
通讯作者：
A. Palomer;M. Cabré;J. Ginesta;D. Mauleón;G. Carganico
中科院分区：
文献类型：
--
作者：
A. Palomer;M. Cabré;J. Ginesta;D. Mauleón;G. Carganico
在有机介质中研究了racc -酮洛芬酯与不同的亲核试剂如醇、胺和水的酶催化反应。优化的参数包括酶、活性底物和溶剂。在本研究中使用的酶中，首选底物是rac-酮洛芬的三氟乙酯（rac-2），其(R)-对映体优先反应。选择的酶是米氏毛霉脂肪酶M-AP-10，以二异丙醚为溶剂效果最好。对于75-150 g底物的分解，我们扩大了三种不同的方法：与1-丁醇酯交换（(S)-酮洛芬收率90%，ee 88%），与2-（2-吡啶基）乙醇酯交换（收率94%，ee 92%），以及在湿有机溶剂中水解（收率93%，ee 97%）。尽管这三种方法获得的化学和光学收率相当，但使用2-（2-吡啶基）乙醇和水解可以更容易地提取和分离所需的(+)-(S)-酮洛芬。©1993 Wiley-Liss, Inc
Enzyme-catalyzed reactions in organic media of rac-ketoprofen esters with different nucleophiles such as alcohols, amines, and water have been studied. Among the parameters optimized are the enzyme, the activated substrate, and the solvent. With the enzymes used in this study the preferred substrate was the trifluoroethyl ester of rac-ketoprofen (rac-2), whose (R)-enantiomer reacted preferentially. The enzyme of choice was the lipase M-AP-10 from Mucor miehei and best results were obtained with diisopropyl ether as solvent. Three different methods have been scaled-up for the resolution of 75–150 g of substrate: transesterification with 1-butanol (90% yield of (S)-ketoprofen, 88% ee), transesterification with 2-(2-pyridyl)ethanol (94% yield, 92% ee), and hydrolysis in wet organic solvent (93% yield, 97% ee). Despite the comparable chemical and optical yields obtained with these three methods, the use of 2-(2-pyridyl)ethanol and the hydrolysis allowed a much easier work-up and isolation of the desired (+)-(S)-ketoprofen. © 1993 Wiley-Liss, Inc.