脂肪酶催化二次动力学拆分制备高光学纯度(S)-萘普生

Lipase-catalyzed Double Kinetic Resolution for the Preparation of High Enantiopurity(S)-Naproxen

设计了一种利用立体选择性相反的两种脂肪酶催化二次动力学拆分,由外消旋萘普生甲酯制备高光学纯度(S)-萘普生的方法。理论曲线预测,与简单的酶促动力学拆分反应相比,二次动力学拆分可以明显提高高光学纯度产物的产率.根据几种脂肪酶在微水/异辛烷双液相反应体系中不对称水解萘普生甲酯的立体选择性和对映体比率(E),首先选用R选择性的固定化南极假丝酵母脂肪酶(Novozym 435)对外消旋萘普生甲酯进行第一次拆分,然后选用S选择性的柱状假丝酵母脂肪酶(CRL)对S过量的剩余底物萘普生甲酯在同样的反应体系中进行第二次拆分.该二次拆分反应对映体过量值为96.8%的(S)-萘普生产率达19.9%.

A R-preference lipase and a S-preference lipase catalyzed double kinetic resolution strategy for preparation of high enantiopurity( S)-Naproxen from racemic Naproxen methyl ester has been designed. The theoretical plots predict that the yield of high enantiopure product was increased obviously by carrying out the double kinetic resolution reaction instead of a single-resolution reaction. According to the strereopreference and enantiomeric ratio( E) of lipases for asymmetric hydrolysis of Naproxen methyl ester in microaqueous-isooctane biphase system,the( S)-Naproxen methyl ester was enriched using immobilized Candida antarctica lipase( Novozym 435) catalyzed hydrolysis and then was hydrolyzed selectively to( S)-Naproxen by Candida rugosa lipase( CRL) in microaqueous-isooctane biphase system. In this way,a yield of 19. 9 % was obtained for( S)-Naproxen with high enantiopurity of 96. 8%.