56715-23-2Relevant academic research and scientific papers
Stereoselective Hydrolysis of Epoxides by reVrEH3, a Novel Vigna radiata Epoxide Hydrolase with High Enantioselectivity or High and Complementary Regioselectivity
Hu, Die,Tang, Cunduo,Li, Chuang,Kan, Tingting,Shi, Xiaoling,Feng, Lei,Wu, Minchen
, p. 9861 - 9870 (2017/11/22)
To provide more options for the stereoselective hydrolysis of epoxides, an epoxide hydrolase (VrEH3) gene from Vigna radiata was cloned and expressed in Escherichia coli. Recombinant VrEH3 displayed the maximum activity at pH 7.0 and 45 °C and high stability at pH 4.5-7.5 and 55 °C. Notably, reVrEH3 exhibited high and complementary regioselectivity toward styrene oxides 1a-3a and high enantioselectivity (E = 48.7) toward o-cresyl glycidyl ether 9a. To elucidate these interesting phenomena, the interactions of the three-dimensional structure between VrEH3 and enantiomers of 1a and 9a were analyzed by molecular docking simulation. Using E. coli/vreh3 whole cells, gram-scale preparations of (R)-1b and (R)-9a were performed by enantioconvergent hydrolysis of 100 mM rac-1a and kinetic resolution of 200 mM rac-9a in the buffer-free water system at 25 °C. These afforded (R)-1b with >99% eep and 78.7% overall yield after recrystallization and (R)-9a with >99% ees, 38.7% overall yield, and 12.7 g/L/h space-time yield.
Asymmetric hydrolysis of styrene oxide by PvEH2, a novel Phaseolus vulgaris epoxide hydrolase with extremely high enantioselectivity and regioselectivity
Li, Chuang,Hu, Die,Zong, Xun-Cheng,Deng, Chao,Feng, Lei,Wu, Min-Chen,Li, Jian-Fang
, p. 57 - 61 (2017/09/08)
A novel EH from Phaseolus vulgaris, PvEH2, was discovered based on the computer-aided analysis, and its encoding gene was cloned and expressed in E. coli Rossetta (DE3). The substrate spectrum of recombinant (re) PvEH2 was assayed, among which the enantiomeric ratio of rePvEH2 towards racemic styrene oxide (rac-1a) was > 200, while its regioselectivity coefficients, αS and βR, towards (S)- and (R)-1a were 99.1 and 69.8%, respectively. The asymmetric hydrolysis of 20 mM rac-1a by rePvEH2-expressing whole cells was performed at 25 °C, retaining (R)-1a with > 99.5% ees and 49.4% yield and producing (R)-phenyl-1,2-ethanediol (1b) with 96.2% eep and 49.7% yield in 40 min.
A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors
Kong, Xu-Dong,Ma, Qian,Zhou, Jiahai,Zeng, Bu-Bing,Xu, Jian-He
supporting information, p. 6641 - 6644 (2014/07/08)
Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates. Hot pockets: Microtuning of the enzyme active pocket gives a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots, and enhanced activity toward bulky substrates was found.
Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(iii)-salen complexes: A practical strategy in the preparation of (S)-metoprolol, (S)-toliprolol and (S)-alprenolol: Computational rationale for enantioselectivity
Roy, Tamal,Barik, Sunirmal,Kumar, Manish,Kureshy, Rukhsana I.,Ganguly, Bishwajit,Khan, Noor-Ul H.,Abdi, Sayed H. R.,Bajaj, Hari C.
, p. 3899 - 3908 (2015/02/19)
A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.
An unusual (R)-selective epoxide hydrolase with high activity for facile preparation of enantiopure glycidyl ethers
Zhao, Jing,Chu, Yan-Yan,Li, Ai-Tao,Ju, Xin,Kong, Xu-Dong,Pan, Jiang,Tang, Yun,Xu, Jian-He
, p. 1510 - 1518 (2011/08/03)
A novel epoxide hydrolase (BMEH) with unusual (R)-enantioselectivity and very high activity was cloned from Bacillus megaterium ECU1001. Highest enantioselectivities (E>200) were achieved in the bioresolution of ortho-substituted phenyl glycidyl ethers and para-nitrostyrene oxide. Worthy of note is that the substrate structure remarkably affected the enantioselectivities of the enzyme, as a reversed (S)-enantiopreference was unexpectedly observed for the ortho-nitrophenyl glycidyl ether. As a proof-of-concept, five enantiopure epoxides (>99% ee) were obtained in high yields, and a gram-scale preparation of (S)-ortho-methylphenyl glycidyl ether was then successfully performed within a few hours, indicating that BMEH is an attractive biocatalyst for the efficient preparation of optically active epoxides. Copyright
Bacillus alcalophilus MTCC10234 catalyzed enantioselective kinetic resolution of aryl glycidyl ethers
Bala, Neeraj,Chimni, Swapandeep Singh,Saini, Harvinder Singh,Chadha, Bhupinder Singh
experimental part, p. 128 - 134 (2010/10/04)
The phenyl glycidyl ether derivatives have been kinetically resolved with the growing cells of Bacillus alcalophilus MTCC10234 yielding (S)-epoxides with up to >99% ee and (R)-diols with up to 89% ee. The enantiomeric ratio (E) of up to 67 has been obtained for biohydrolysis process. The effect of different substituents of phenyl glycidyl ether on the biocatalytic efficiency of B. alcalophilus MTCC10234 showed preference for methyl- and chloro-substituted aryl glycidyl ether derivatives whereas nitro-derivatives were transformed at a slower rate. 2,6-Dimethylphenyl glycidyl ether which contains a bulky aryl group having methyl group on both the ortho positions was resolved with an E=39.
Directed evolution of an enantioselective epoxide hydrolase: Uncovering the source of enantioselectivity at each evolutionary stage
Reetz, Manfred T.,Bocola, Marco,Wang, Li-Wen,Sanchis, Joaquin,Cronin, Annette,et al.
supporting information; experimental part, p. 7334 - 7343 (2009/10/17)
Directed evolution of enzymes as enantioselective catalysts in organic chemistry is an alternative to traditional asymmetric catalysis using chiral transition-metal complexes or organocatalysts, the different approaches often being complementary. Moreover, directed evolution studies allow us to learn more about how enzymes perform mechanistically. The present study concerns a previously evolved highly enantioselective mutant of the epoxide hydrolase from Aspergillus niger in the hydrolytic kinetic resolution of racemic glycidyl phenyl ether. Kinetic data, molecular dynamics calculations, molecular modeling, inhibition experiments, and X-raystructural work for the wild-type (WT) enzyme and the best mutant revea l the basis of the large increase in enantioselectivity (E = 4.6 versus E = 115). The overall structures of the WT and the mutant are essentially identical, but dramatic differences are observed in the active site asrevealed by the X-ray structures. All of the experimental and computati onal results support a model in which productive positioning of the preferred (S)-glycidyl phenyl ether, but not the (R)-enantiomer, forms the basis of enhanced enantioselectivity. Predictions regarding substrate scope and enantioselectivity of the best mutant are shown to be possible.
Hydrolytic kinetic resolution of terminal epoxides catalyzed by novel bimetallic chiral Co (salen) complexes
Kawthekar, Rahul B.,Kim, Geon-Joong
, p. 1236 - 1248 (2008/09/18)
Novel bimetallic chiral Co (salen) complexes bearing transition-metal salts have been synthesized. The easily prepared complexes exhibited very high catalytic reactivity and enantioselectivity in hydrolytic kinetic resolution (HKR) of racemic terminal epoxides and consequently provided enantiomerically enriched epoxides (up to 99% ee). Copyright Taylor & Francis Group, LLC.
Synthesis of optically pure terminal epoxide and 1,2-diol via hydrolytic kinetic resolution catalyzed by new heterometallic salen complexes
Thakur, Santosh Singh,Chen, Shu-Wei,Li, Wenji,Shin, Chang-Kyo,Koo, Yoon-Mo,Kim, Geon-Joong
, p. 2371 - 2383 (2007/10/03)
The inactive chiral (salen)Co complex is easily activated by InCl 3 and TlCl3 Lewis acids by forming heterometallic salen complexes. These complexes show very high catalytic activity for the synthesis of enantiomerically enriched terminal epoxides (>99% ee) and 1,2-diols simultaneously via hydrolytic kinetic resolution. Strong synergistic effects of different Lewis acids, Co-In and Co-Tl, were exhibited in the catalytic process. The system described is very simple and efficient. Copyright Taylor & Francis Group, LLC.
A new dinuclear chiral salen complexes for asymmetric ring opening and closing reactions: Synthesis of valuable chiral intermediates
Thakur, Santosh Singh,Chen, Shu-Wei,Li, Wenji,Shin, Chang-Kyo,Kim, Seong-Jin,Koo, Yoon-Mo,Kim, Geon-Joong
, p. 1862 - 1872 (2007/10/03)
A new dinuclear chiral Co(salen) complexes bearing group 13 metals have been synthesized and characterized. The easily prepared complexes exhibited very high catalytic reactivity and enantioselectivity for the asymmetric ring opening of epoxides with H2O, chloride ions and carboxylic acids and consequently provide enantiomerically enriched terminal epoxides (>99% ee). It also catalyzes the asymmetric cyclization of ring opened product, to prepare optically pure terminal epoxides in one step. The homogeneous dinuclear chiral Co(salen) have been covalently immobilized on MCM-41. The potential benefits of heterogenization include facilitation of catalyst separation and recyclability requiring very simple techniques. The system described is very efficient.
