(S)-2-chlorophenylglycine methyl ester ((S)-1) is a key chiral building block of clopidogrel, which is a widely administered antiaggregatory and antithrombotic drug. Herein, Protease 6SD was covalently immobilized on multi-walled carbon nanotubes (MWCNT), and the as-prepared immobilizate P-6SD@NH₂-MWCNT was applied in the enantioselective resolution of (R,S)-1 to yield (S)-1. In order to overcome the poor solubility of (R,S)-1 in aqueous solution, a novel triphasic reaction system constituting P-6SD@NH₂-MWCNT, aqueous phase and methyl tert-butyl ether (MTBE) as the organic phase was constructed, which simultaneously improved the substrate solubility and the immobilizate recyclability. Under the optimized reaction conditions, P-6SD@NH₂-MWCNT catalyzed 10 mM (R,S)-1 for 2 h, yielding optically pure (S)-1 (>99.0 % ee_s) with 70.74 % conversion of the (R,S)-1. Moreover, P-6SD@NH₂-MWCNT can be reused for 15 batches, displaying an exquisite recycling performance. It is for the first time that enantiomerically pure (S)-1 was successfully synthesized by protease-catalyzed one-step resolution.

( S )-2-氯苯基甘氨酸甲酯 (( S )- 1 ) 是氯吡格雷的关键手性构件，氯吡格雷是一种广泛使用的抗凝集和抗血栓形成药物。在本文中，蛋白酶 6SD 共价固定在多壁碳纳米管 (MWCNT) 上，并将所制备的固定物 P-6SD@NH ₂ -MWCNT 应用于 ( R,S )- 1的对映选择性拆分以得到 ( S ) - 1。为了克服( R,S )- 1在水溶液中溶解度差的问题，一种由P-6SD@NH ₂ -MWCNT、水相和甲基叔丁基组成的新型三相反应体系构建了-丁基醚（MTBE）作为有机相，同时提高了底物的溶解性和固定物的可回收性。在优化的反应条件下，P-6SD@NH ₂ -MWCNT 催化 10 mM ( R,S )- 1 2 h，产生光学纯的 ( S )- 1 (> 99.0 % ee _s )，( R,S )- 1。此外，P-6SD@NH ₂ -MWCNT 可重复使用 15 批，显示出优良的回收性能。首次对映体纯 ( S ) -1 通过蛋白酶催化一步拆分成功合成。