文献类型：期刊文献

中文题名：非达司他中间体的酶法拆分

英文题名：Optical Resolution of Intermediate of Fidarestat by Lipase

作者：任宇红[1];黄磊[1];张德荣[1];魏东芝[1]

机构：[1]华东理工大学生物反应器工程国家重点实验室,上海200237

年份：2008

卷号：25

期号：4

起止页码：329

中文期刊名：精细化工

外文期刊名：Fine Chemicals

收录：CSTPCD;;Scopus;北大核心:【北大核心2004】；CSCD:【CSCD2011_2012】；

语种：中文

中文关键词：脂肪酶;拆分;酶促水解;非达司他中间体;生物工程

外文关键词：lipase ; optical resolution ; enzyme urging hydrolysis ; intermediate of fidarestat ; biological engineering

摘要：(2S)-6-氟-3,4-二氢-4-氧代-2H-1-苯并吡喃-2-羧酸是合成非达司他(一种口服醛糖还原酶抑制剂)关键中间体。该研究使用脂肪酶Novozym 435,对(±)-6-氟-3,4-二氢-4-氧代-2H-1-苯并吡喃-2-羧酸甲酯进行拆分,并对拆分反应条件进行了优化,确定了拆分的最适反应条件:乙腈-水溶液为溶剂,V(水)∶V(乙腈)=1∶4,m(酶)∶m(底物)=1∶10,在pH=7.0,温度40℃,时间为6 h条件下,得到的(2S)-6-氟-3,4-二氢-4-氧代-2H-1-苯并吡喃-2-羧酸的总收率为32.5%,对映体过量值为92.1%,为非达司他的制备提供了一条可行途径。
（2S） -6-Fluoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid is the key intermediate of fidarestat（ a kind of peroral aldose reductase inhibitory）. Novozym 435 was screened as the catalyst, meanwhile,Novozyme 435 can effectively resolute （ ＋ ）-6-fluoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2- carboxylic acid methyl esters. Under the optimal conditions that acetonitrile-water was used as the solvent, V（ water）/V （ acetonitrile ） = 0. 25, m （ lipase）/m （ butyrate ） = 0. 1, pH = 7.0, the reaction temperature was around 40 ℃, and the reaction time was about 6. 0 h, the enantiomeric excess of （2S）-6- fluoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid could reach 92.1 % and the yield was about 32. 5%. This work provides a feasible approach to the enzymatic production of fidarestat.