Tsai S W, Tsai C S, Chang C S
Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Appl Biochem Biotechnol. 1999 Jun;80(3):205-19. doi: 10.1385/abab:80:3:205.
A lipase-catalyzed enantioselective transesterification process was developed for the synthesis of (S)-naproxen 2-N-morpholinoethyl ester prodrug from racemic 2,2,2-trifluoroethyl naproxen ester in organic solvents. By selecting isooctane and 37 degrees C as the best solvent and temperature, the apparent fits of the initial conversion rates for transesterification and hydrolysis side reaction suggest a ping-pong Bi-Bi enzymatic mechanism with the alcohol as a competitive enzyme inhibitor. Improvements in the initial conversion rate and the productivity for the desired (S)-ester product were obtained after comparing with the result of an enantioselective esterification process. Studies of water content in isooctane and alcohol containing various N,N-dialkylamino groups on the enzyme activity and enantioselectivity, as well as the recovery of (S)-ester product by using extraction, were also reported.
开发了一种脂肪酶催化的对映选择性酯交换过程，用于在有机溶剂中由外消旋萘普生2,2,2-三氟乙酯合成(S)-萘普生2-N-吗啉代乙酯前药。通过选择异辛烷和37℃作为最佳溶剂和温度，酯交换和水解副反应的初始转化率的表观拟合表明了一种以醇为竞争性酶抑制剂的乒乓双底物酶机制。与对映选择性酯化过程的结果相比，提高了所需(S)-酯产物的初始转化率和生产率。还报道了研究异辛烷和含有各种N,N-二烷基氨基的醇中的水含量对酶活性和对映选择性的影响，以及通过萃取回收(S)-酯产物。
