Lipase-catalyzed hydrolytic resolution of (R,S)-naproxen amides in water-saturated organic solvents

• Main Authors: Ying Ju Chen, 陳盈如
• Other Authors: Shau Wai Tsai
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/68297044531068612450

碩士 === 長庚大學 === 生化與生醫工程研究所 === 95 === The aim of this study is to use (R,S)-naproxen imidazoyl amide, (R,S)-naproxen 2-methylimidazoyl amide, and (R,S)-naproxen 1,2,4-triazoyl amide as the substrates to perform lipase-catalyzed hydrolytic resolution in water-saturated organic solvents. The results suggest that lipases from different origins have no enantioselectivity (E~1) for (R,S)-naproxen imidazoyl amide. Furthermore, the non-enantioselectivity for the amide remains unchanged by using medium engineering approaches including changes of organic solvents, temperatures, and addition of various additives. According to previous reports, (R,S)-naproxen 2,2,2-trifluoroethyl ester and (R,S)-naproxen 2,2,2-trifluoroethyl thioester as the substrates for carrying out lipase-catalyzed hydrolysis resolution have quite high enantioselectivity (E > 100). However, it is not valid for (R,S)-naproxen imidazoyl amide. Therefore, we try to employ (R,S)-naproxen 1,2,4-triazoyl amide or (R,S)-naproxen 2-methylimidazoyl amide having a similar structure to (R,S)-naproxen imidazoyl amide as the substrate to compare the enzymatic behaviors. The kinetic analysis indicates that replacement of the leaving group of (R,S)-naproxen ester and thioester with imidazole, 1,2,4-triazole or 2-methylimidazole moiety has profound effects on the kinetic constants of the hydrolytic reactions.