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Chemoenzymatic synthesis of (R)- and (S)-propranolol using an engineered epoxide hydrolase with a high turnover number
Alternative Title使用基因工程改造的环氧水解酶可以搞转换数来实现(R)、(S)型普洛萘尔的化学酶法合成
Kong XD(孔旭东)1; Yu HL(郁惠蕾)1; Yang S(杨晟)1; Zhou JH(周佳海)1; Ceng BB(曾步兵)1; Xu JH(许建和)1
2015
Source PublicationJ. Mol. Catal. B-Enzym.
Volume122Pages:275-281
AbstractSimultaneous synthesis of the R- and S-enantiomers of biologically active propranolol, a typical p-blocker, was achieved in high optical purity via an epoxide hydrolase-catalyzed resolution of racemic alpha-naphthyl glycidyl ether (rac-1). A preparative resolution of 100 g/L rac-1 was accomplished with high enantio-selectivity (E=92) using a variant of Bacillus megaterium epoxide hydrolase (BmEHF(128T)). A biphasic system (isopropyl ether/isooctane/aqueous) was used, in which the product 3-(1'-naphthyloxy)-propane-1,2-dial (2) precipitated instantly, facilitating its separation and increasing the enantiopurity of (R)-2 (>99.5% ee). This enzymatic resolution had a total turnover number of 70,000, affording enantiopure epoxide (S)-1 (>99% ee) and 1,2-diol (R)-2 (>99% ee) in 45.3% and 42.4% yields, respectively. (R)-2 and (S)-1 were subsequently converted to (R)- and (S)-propranolol (3) (>99% cc) in overall yields of 31.4% and 44.8%. To the best of our knowledge, this is the best case for enzymatic resolution of rac-1 using an epoxide hydrolase, giving high space-time yields [136 g L-1 days(-1) for (S)-1 and 139 g L-1 days(-1) for (R)-2] under mild reaction conditions. It provides a new and eco-friendly route that complements other methods using organometallic catalysts. (C) 2015 Elsevier B.V. All rights reserved.
Subtype论文
Subject Area生命有机化学
DOI10.1016/j.molcatb.2015.10.005
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000366078800034
Citation statistics
Cited Times:5[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/39543
Collection生命有机化学国家重点实验室
Corresponding AuthorXu JH(许建和)
Affiliation1.华东理工大学
2.中科院上海有机化学研究所, 生命有机化学国家重点实验室
3.中科院上海生命科学研究院植物生理生态研究所
Recommended Citation
GB/T 7714
Kong XD,Yu HL,Yang S,et al. Chemoenzymatic synthesis of (R)- and (S)-propranolol using an engineered epoxide hydrolase with a high turnover number[J]. J. Mol. Catal. B-Enzym.,2015,122:275-281.
APA 孔旭东,郁惠蕾,杨晟,周佳海,曾步兵,&许建和.(2015).Chemoenzymatic synthesis of (R)- and (S)-propranolol using an engineered epoxide hydrolase with a high turnover number.J. Mol. Catal. B-Enzym.,122,275-281.
MLA 孔旭东,et al."Chemoenzymatic synthesis of (R)- and (S)-propranolol using an engineered epoxide hydrolase with a high turnover number".J. Mol. Catal. B-Enzym. 122(2015):275-281.
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