Journal
JOURNAL OF BIOTECHNOLOGY
Volume 325, Issue -, Pages 294-302Publisher
ELSEVIER
DOI: 10.1016/j.jbiotec.2020.10.007
Keywords
(S)-2-chlorophenylglycine methyl ester; Enantioselective bioresolution; Protease; Immobilization; Triphasic system
Categories
Funding
- Natural Science Foundation of China [21878274, 21476209]
- Natural Science Foundation of Zhejiang Province [LQ18C010005]
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In this study, Protease 6SD was immobilized on multi-walled carbon nanotubes to achieve enantioselective resolution of (R,S)-1 to yield optically pure (S)-1, improving substrate solubility and catalyst recyclability.
(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.Y
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