通过高效脂肪酶与酸碱催化偶联实现外消旋布洛芬的循环拆分

Cyclic resolution of racemic ibuprofen via coupled efficient lipase and acid-base catalysis.

作者信息

Liu Ying, Wang Fang, Tan Tianwei

机构信息

School of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.

出版信息

Chirality. 2009 Mar;21(3):349-53. doi: 10.1002/chir.20578.

DOI:10.1002/chir.20578

PMID:18571801

Abstract

Extracellular lipase LIP prepared in our lab from the yeast Yarrowia lipolytica was used for the resolution of racemic ibuprofen. The (S)-enantiomer was preferred by lipase LIP, and the unreacted (R)-enantiomer was extracted and racemized in basic solvent-water medium to be re-resolved. Solvent, content of solvent, base concentration, and temperature have a strong effect on racemization. The (S)-ester was separated and hydrolyzed to (S)-ibuprofen in acidic dimethyl sulfoxide-water mixture containing 70% dimethyl sulfoxide. The high purity (S)-ibuprofen (ee = 0.98) was obtained using lipase LIP to catalyze hydrolysis of (S)-ester in 0.1 M phosphate buffer (pH = 8).

摘要

我们实验室从解脂耶氏酵母中制备的胞外脂肪酶LIP用于拆分外消旋布洛芬。脂肪酶LIP更倾向于作用(S)-对映体，未反应的(R)-对映体被萃取出来，并在碱性溶剂-水介质中进行外消旋化，以便再次拆分。溶剂、溶剂含量、碱浓度和温度对外消旋化有很大影响。(S)-酯在含70%二甲亚砜的酸性二甲亚砜-水混合物中被分离并水解为(S)-布洛芬。使用脂肪酶LIP在0.1 M磷酸盐缓冲液（pH = 8）中催化(S)-酯的水解，得到了高纯度的(S)-布洛芬（对映体过量值ee = 0.98）。