- The Stereoselective Oxidation of para-Substituted Benzenes by a Cytochrome P450 Biocatalyst
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The serine 244 to aspartate (S244D) variant of the cytochrome P450 enzyme CYP199A4 was used to expand its substrate range beyond benzoic acids. Substrates, in which the carboxylate group of the benzoic acid moiety is replaced were oxidised with high activity by the S244D mutant (product formation rates >60 nmol.(nmol-CYP)?1.min?1) and with total turnover numbers of up to 20,000. Ethyl α-hydroxylation was more rapid than methyl oxidation, styrene epoxidation and S-oxidation. The S244D mutant catalysed the ethyl hydroxylation, epoxidation and sulfoxidation reactions with an excess of one stereoisomer (in some instances up to >98 %). The crystal structure of 4-methoxybenzoic acid-bound CYP199A4 S244D showed that the active site architecture and the substrate orientation were similar to that of the WT enzyme. Overall, this work demonstrates that CYP199A4 can catalyse the stereoselective hydroxylation, epoxidation or sulfoxidation of substituted benzene substrates under mild conditions resulting in more sustainable transformations using this heme monooxygenase enzyme.
- Chao, Rebecca R.,Lau, Ian C.-K.,Coleman, Tom,Churchman, Luke R.,Child, Stella A.,Lee, Joel H. Z.,Bruning, John B.,De Voss, James J.,Bell, Stephen G.
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p. 14765 - 14777
(2021/09/14)
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- Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max
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A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, αS = 93.7% and βR = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (kcatS/KmS = 2.50 mM?1 s?1) of purified GmEH3 for (S)-5a was slightly higher than that (kcatR/KmR = 1.52 mM?1 s?1) for (R)-5a, whereas the kcat/Km (5.16 mM?1 s?1) for (S)-7a was much higher than that (0.09 mM?1 s?1) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 °C for 1.5 h afforded (R)-5b with 90.2% eep and 95.4% yieldp, while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ees and 43.2% yields. Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.
- Zhang, Chen,Li, Chuang,Zhu, Xiu-xiu,Liu, You-yi,Zhao, Jun,Wu, Min-chen
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p. 2795 - 2803
(2020/09/01)
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- Manipulating regioselectivity of an epoxide hydrolase for single enzymatic synthesis of (: R)-1,2-diols from racemic epoxides
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Both the activity and regioselectivity of Phaseolus vulgaris epoxide hydrolase were remarkably improved via reshaping two substrate tunnels based on rational design. The elegant one-step enantioconvergent hydrolysis of seven rac-epoxides was achieved by single mutants, allowing green and efficient access to valuable (R)-1,2 diols with high eep (90.1-98.3%) and yields.
- Hu, Die,Zong, Xun-Cheng,Xue, Feng,Li, Chuang,Hu, Bo-Chun,Wu, Min-Chen
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supporting information
p. 2799 - 2802
(2020/03/13)
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- Reprogramming Epoxide Hydrolase to Improve Enantioconvergence in Hydrolysis of Styrene Oxide Scaffolds
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Enantioconvergent hydrolysis by epoxide hydrolase is a promising method for the synthesis of important vicinal diols. However, the poor regioselectivity of the naturally occurring enzymes results in low enantioconvergence in the enzymatic hydrolysis of styrene oxides. Herein, modulated residue No. 263 was redesigned based on structural information and a smart variant library was constructed by site-directed modification using an “optimized amino acid alphabet” to improve the regioselectivity of epoxide hydrolase from Vigna radiata (VrEH2). The regioselectivity coefficient (r) of variant M263Q for the R-isomer of meta-substituted styrene oxides was improved 40–63-fold, and variant M263V also exhibited higher regioselectivity towards the R-isomer of para-substituted styrene oxides compared with the wild type, which resulted in improved enantioconvergence in hydrolysis of styrene oxide scaffolds. Structural insight showed the crucial role of residue No. 263 in modulating the substrate binding conformation by altering the binding surroundings. Furthermore, increased differences in the attacking distance between nucleophilic residue Asp101 and the two carbon atoms of the epoxide ring provided evidence for improved regioselectivity. Several high-value vicinal diols were readily synthesized (>88% yield, 90%–98% ee) by enantioconvergent hydrolysis using the reprogrammed variants. These findings provide a successful strategy for enhancing the enantioconvergence of native epoxide hydrolases through key single-site mutation and more powerful enzyme tools for the enantioconvergent hydrolysis of styrene oxide scaffolds into single (R)-enantiomers of chiral vicinal diols. (Figure presented.).
- Li, Fu-Long,Qiu, Yan-Yan,Zheng, Yu-Cong,Chen, Fei-Fei,Kong, Xu–Dong,Xu, Jian-He,Yu, Hui-Lei
-
supporting information
p. 4699 - 4706
(2020/09/21)
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- Chiral Ion-Pair Organocatalyst-Promoted Efficient Enantio-selective Reduction of α-Hydroxy Ketones
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The enantioselective reduction of α-hydroxy ketones with catecholborane has been developed employing 5 mol% of an 1,1′-bi-2-naphthol (BINOL)-derived ion-pair organocatalyst. This methodology provides a straightforward access to the corresponding aromatic 1,2-diols in high yields (up to 90%) with excellent enantioselectivities (up to 97%). Furthermore, the α-amino ketones also could be reduced with moderate ee values under mild reaction condition. (Figure presented.).
- Zhang, Yiliang,He, Li,Shi, Lei
-
supporting information
p. 1926 - 1931
(2018/03/27)
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- Cis -Oxoruthenium complexes supported by chiral tetradentate amine (N4) ligands for hydrocarbon oxidations
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We report the first examples of ruthenium complexes cis-[(N4)RuIIICl2]+ and cis-[(N4)RuII(OH2)2]2+ supported by chiral tetradentate amine ligands (N4), together with a high-valent cis-dioxo complex cis-[(N4)RuVI(O)2]2+ supported by the chiral N4 ligand mcp (mcp = N,N′-dimethyl-N,N′-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine). The X-ray crystal structures of cis-[(mcp)RuIIICl2](ClO4) (1a), cis-[(Me2mcp)RuIIICl2]ClO4 (2a) and cis-[(pdp)RuIIICl2](ClO4) (3a) (Me2mcp = N,N′-dimethyl-N,N′-bis((6-methylpyridin-2-yl)methyl)cyclohexane-1,2-diamine, pdp = 1,1′-bis(pyridin-2-ylmethyl)-2,2′-bipyrrolidine)) show that the ligands coordinate to the ruthenium centre in a cis-α configuration. In aqueous solutions, proton-coupled electron-transfer redox couples were observed for cis-[(mcp)RuIII(O2CCF3)2]ClO4 (1b) and cis-[(pdp)RuIII(O3SCF3)2]CF3SO3 (3c′). Electrochemical analyses showed that the chemically/electrochemically generated cis-[(mcp)RuVI(O)2]2+ and cis-[(pdp)RuVI(O)2]2+ complexes are strong oxidants with E° = 1.11-1.13 V vs. SCE (at pH 1) and strong H-atom abstractors with DO-H = 90.1-90.8 kcal mol-1. The reaction of 1b or its (R,R)-mcp counterpart with excess (NH4)2[CeIV(NO3)6] (CAN) in aqueous medium afforded cis-[(mcp)RuVI(O)2](ClO4)2 (1e) or cis-[((R,R)-mcp)RuVI(O)2](ClO4)2 (1e?), respectively, a strong oxidant with E(RuVI/V) = 0.78 V (vs. Ag/AgNO3) in acetonitrile solution. Complex 1e oxidized various hydrocarbons, including cyclohexane, in acetonitrile at room temperature, affording alcohols and/or ketones in up to 66% yield. Stoichiometric oxidations of alkenes by 1e or 1e? in tBuOH/H2O (5:1 v/v) afforded diols and aldehydes in combined yields of up to 98%, with moderate enantioselectivity obtained for the reaction using 1e?. The cis-[(pdp)RuII(OH2)2]2+ (3c)-catalysed oxidation of saturated C-H bonds, including those of ethane and propane, with CAN as terminal oxidant was also demonstrated.
- Tse, Chun-Wai,Liu, Yungen,Wai-Shan Chow, Toby,Ma, Chaoqun,Yip, Wing-Ping,Chang, Xiao-Yong,Low, Kam-Hung,Huang, Jie-Sheng,Che, Chi-Ming
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p. 2803 - 2816
(2018/03/21)
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- Kinetic Resolution of 1,2-Diols via NHC-Catalyzed Site-Selective Esterification
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A kinetic resolution of 1,2-diols bearing both a secondary and a primary alcohol motif through an N-heterocyclic carbene-catalyzed oxidative acylation reaction has been developed. A site- and enantioselective esterification reaction is involved for this process. Both the monoacylated diols obtained and the remaining enantioenriched 1,2-diols are versatile building blocks for the preparation of functional molecules with proven biological activities.
- Liu, Bin,Yan, Jiekuan,Huang, Ruoyan,Wang, Weihong,Jin, Zhichao,Zanoni, Giuseppe,Zheng, Pengcheng,Yang, Song,Chi, Yonggui Robin
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supporting information
p. 3447 - 3450
(2018/06/26)
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- Stereoselective Hydrolysis of Epoxides by reVrEH3, a Novel Vigna radiata Epoxide Hydrolase with High Enantioselectivity or High and Complementary Regioselectivity
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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.
- Hu, Die,Tang, Cunduo,Li, Chuang,Kan, Tingting,Shi, Xiaoling,Feng, Lei,Wu, Minchen
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p. 9861 - 9870
(2017/11/22)
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- Highly selective anti-Prelog synthesis of optically active aryl alcohols by recombinant Escherichia coli expressing stereospecific alcohol dehydrogenase
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Biocatalytic asymmetric synthesis has been widely used for preparation of optically active chiral alcohols as the important intermediates and precursors of active pharmaceutical ingredients. However, the available whole-cell system involving anti-Prelog specific alcohol dehydrogenase is yet limited. A recombinant Escherichia coli system expressing anti-Prelog stereospecific alcohol dehydrogenase from Candida parapsilosis was established as a whole-cell system for catalyzing asymmetric reduction of aryl ketones to anti-Prelog configured alcohols. Using 2-hydroxyacetophenone as the substrate, reaction factors including pH, cell status, and substrate concentration had obvious impacts on the outcome of whole-cell biocatalysis, and xylose was found to be an available auxiliary substrate for intracellular cofactor regeneration, by which (S)-1-phenyl-1,2-ethanediol was achieved with an optical purity of 97%e.e. and yield of 89% under the substrate concentration of 5?g/L. Additionally, the feasibility of the recombinant cells toward different aryl ketones was investigated, and most of the corresponding chiral alcohol products were obtained with an optical purity over 95%e.e. Therefore, the whole-cell system involving recombinant stereospecific alcohol dehydrogenase was constructed as an efficient biocatalyst for highly enantioselective anti-Prelog synthesis of optically active aryl alcohols and would be promising in the pharmaceutical industry.
- Li, Ming,Nie, Yao,Mu, Xiao Qing,Zhang, Rongzhen,Xu, Yan
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p. 429 - 433
(2016/08/11)
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- Structurally Defined Molecular Hypervalent Iodine Catalysts for Intermolecular Enantioselective Reactions
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Molecular structures of the most prominent chiral non-racemic hypervalent iodine(III) reagents to date have been elucidated for the first time. The formation of a chirally induced supramolecular scaffold based on a selective hydrogen-bonding arrangement provides an explanation for the consistently high asymmetric induction with these reagents. As an exploratory example, their scope as chiral catalysts was extended to the enantioselective dioxygenation of alkenes. A series of terminal styrenes are converted into the corresponding vicinal diacetoxylation products under mild conditions and provide the proof of principle for a truly intermolecular asymmetric alkene oxidation under iodine(I/III) catalysis.
- Haubenreisser, Stefan,W?ste, Thorsten H.,Martnez, Claudio,Ishihara, Kazuaki,Muiz, Kilian
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supporting information
p. 413 - 417
(2016/01/25)
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- Production Of Enantiopure alpha-Hydroxy Carboxylic Acids From Alkenes By Cascade Biocatalysis
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The invention provides compositions comprising an alkene epoxidase and a selective epoxide hydrolase, such as a recombinant microorganism comprising a first heterologous nucleic acid encoding an alkene epoxidase and a second heterologous nucleic acid encoding a selective epoxide hydrolase. Exemplary alkene epoxidases include StyAB, while exemplary selective epoxide hydrolases include epoxide hydrolases from Sphingomonas, Solanum tuberosum, or Aspergillus. The invention also provides non-toxic methods of making enantiomerically pure vicinal diols or enantiomerically pure alpha-hydroxy carboxylic acids using these compositions and microorganisms.
- -
-
Paragraph 0065-0067
(2016/05/02)
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- Enantioselective Vicinal Diacetoxylation of Alkenes under Chiral Iodine(III) Catalysis
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A procedure for the intermolecular enantioselective dioxygenation of alkenes under iodine(III) catalysis has been developed. This protocol employs Selectfluor as the terminal oxidant together with a defined C 2-symmetric aryl iodide as the organocatalyst. This enantioselective reaction proceeds under mild conditions and converts a series of terminal and internal styrenes into the corresponding vicinal diacetoxylation products with up to 96% ee.
- W?ste, Thorsten H.,Mu?iz, Kilian
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p. 816 - 827
(2016/03/15)
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- Enantioselective trans-dihydroxylation of aryl olefins by cascade biocatalysis with recombinant escherichia coli coexpressing monooxygenase and epoxide hydrolase
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Cascade biocatalysis via intracellular epoxidation and hydrolysis was developed as a green and efficient method for enantioselective dihydroxylation of aryl olefins to prepare chiral vicinal diols in high ee and high yield. Escherichia coli (SSP1) coexpressing styrene monooxygenase (SMO) and epoxide hydrolase SpEH was developed as a simple and efficient biocatalyst for S-enantioselective dihydroxylation of terminal aryl olefins 1a-15a to give (S)-vicinal diols 1c-15c in high ee (97.5-98.6% for 10 diols; 92.2-93.9% for 3 diols) and high yield (91-99% for 6 diols; 86-88% for 2 diols; 67% for 3 diols). Combining SMO and epoxide hydrolase StEH showing complementary regioselectivity to SpEH as a biocatalyst for the cascade biocatalysis gave rise to R-enantioselective dihydroxylation of aryl olefins, being the first example of this kind of reversing the overall enantioselectivity of cascade biocatalysis. E. coli (SST1) coexpressing SMO and StEH was also engineered as a green and efficient biocatalyst for R-dihydroxylation of terminal aryl olefins 1a-15a to give (R)-vicinal diols 1c-15c in high ee (94.2-98.2% for 7 diols; 84.2-89.9% for 6 diols) and high yield (90-99% for 6 diols; 85-89% for 5 diols; 65% for 1 diol). E. coli (SSP1) and E. coli (SST1) catalyzed the trans-dihydroxylation of trans-aryl olefin 16a and cis-aryl olefin 17a with excellent and complementary stereoselectivity, giving each of the four stereoisomers of 1-phenyl-1,2- propanediol 16c in high ee and de, respectively. Both strains catalyzed the trans-dihydroxylation of aryl cyclic olefins 18a and 19a to afford the same trans-cyclic diols (1R,2R)-18c and (1R,2R)-19c, respectively, in excellent ee and de. This type of cascade biocatalysis provides a tool that is complementary to Sharpless dihydroxylation, accepting cis-alkene and offering enantioselective trans-dihydroxylation.
- Wu, Shuke,Chen, Yongzheng,Xu, Yi,Li, Aitao,Xu, Qisong,Glieder, Anton,Li, Zhi
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p. 409 - 420
(2014/03/21)
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- Transition-metal-free and chemoselective NaOtBu-O 2-mediated oxidative cleavage reactions of vic-1,2-diols to carboxylic acids and mechanistic insight into the reaction pathways
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A method for efficient oxidative cleavage of vic-1,2-diols using a NaO tBu-O2 system resulted in the formation of carboxylic acids in high yields. The present protocol is an eco-friendly alternative to a conventional transition-metal-based method. This new strategy allows large-scale production with nonchromatographic purification while also suppressing competitive reaction pathway such as benzilic acid rearrangement.
- Kim, Sun Min,Kim, Dong Wan,Yang, Jung Woon
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supporting information
p. 2876 - 2879
(2014/06/23)
-
- Regio- and enantio-selective oxidation of diols by Candida parapsilosis ATCC 7330
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Selectivity between primary and secondary alcohols was observed in oxidation using whole cells of Candida parapsilosis ATCC 7330, where the secondary alcohol was preferentially oxidized. In racemic sec alcohols, the 'R' enantiomer was selectively oxidized to the corresponding keto alcohol (yield = 18-54%) leaving the 'S' diol (yield = 31-69% and enantiomeric excess from 14% to >99%). A biphasic system consisting of isooctane-water (48 : 2 v/v) was used as a medium for biotransformation at 25 °C. This is the first report of the regio- and enantio-selective oxidation of diols using C. parapsilosis ATCC 7330.
- Sivakumari, Thakkellapati,Chadha, Anju
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p. 60526 - 60533
(2015/02/19)
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- Highly enantioselective deracemization of 1-phenyl-1,2-ethanediol and its derivatives by stereoinversion using Candida albicans in a one-pot process
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A very simple methodology was developed to transform racemic 1-(4-substitutedphenyl)-1,2-ethanediols using resting cells of Candida albicans CCT 0776 through a one-pot two-step process in which the (R)-stereoisomer was completely oxidized to the corresponding substituted-α-hydroxyacetophenones, which were completely reduced to produce (S)-1-(4-substitutedphenyl)-1,2-ethanediols in good isolated yield (60-85%) and with high enantiomeric excess (99% ee). The overall process corresponded to an enantioselective deracemization by stereoinversion of the (R)-enantiomer. The process was not achieved for other similar 1,2-diols using the same reaction conditions, which indicates a structural restriction of substrates by the active pocket of the enzymes of C. albicans involved in the stereoinversion process.
- Cazetta, Tarcila,Moran, Paulo J.S.,Rodrigues, J. Augusto R.
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p. 178 - 183
(2014/12/11)
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- Directed evolution of metagenome-derived epoxide hydrolase for improved enantioselectivity and enantioconvergence
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We performed a directed evolution study with a metagenome-derived epoxide hydrolase (EH), termed Kau2. Homology models of Kau2 were built; we selected one of them and used it as a guide for saturation mutagenesis experiments targeted at specific residues within the large substrate binding pocket. During the molecular evolution process, we found several enzyme variants with higher enantioselectivity or enhanced enantioconvergence toward para-Chlorostyrene oxide. Improved enantioselectivities by up to a factor of 5, reaching an E-value of up to 130 with the R-enantiomer as the residual epoxide, were achieved by replacing amino acid pairs at the positions 110 and 113, or 290 and 291, which are positions located in the vicinity of two presumed binding sites for the epoxide enantiomers. The (R)-para-Chlorophenylethane-1,2-diol product exhibited a high enantiomeric excess (ee) of 97% at 50% conversion of the racemic epoxide for the most enantioselective variant. Further, five amino acid substitutions were sufficient to substantially increase the degree of enantioconvergence and to lower the E-value to 17 for the final evolved EH variant, enabling the production of the R-diol with an ee-value of 93% at 28 °C in a complete conversion of the racemic epoxide. Higher eep-values of up to 97% were determined in enantioconvergent reactions using lower temperatures. The EH activities of whole cells were found to be within the range of 74-125% of the wild-type activity for all investigated variants. We show in this report that the metagenome-derived Kau2 EH is amenable to the redesign of its enantioselectivity and regioselectivity properties by directed evolution using a homology model as a guide. The generated enzyme variants should be useful for the production of the chiral building blocks (R)-para-Chlorostyrene oxide and (R)-para-Chlorophenylethane-1,2-diol.
- Kotik, Michael,Zhao, Wei,Iacazio, Gilles,Archelas, Alain
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- Asymmetric diboration of terminal alkenes with a rhodium catalyst and subsequent oxidation: Enantioselective synthesis of optically active 1,2-diols
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Pin it down: A highly enantioselective diboration of terminal alkenes with chiral 1 and bis(pinacolato)diboron (B2pin2) was realized. Subsequent oxidation of the diboron adducts with sodium peroxoborate readily gave the corresponding optically active 1,2-diols in high yields and high enantioselectivities. Copyright
- Toribatake, Kenji,Nishiyama, Hisao
-
supporting information
p. 11011 - 11015
(2013/10/22)
-
- Biocatalytic reduction of prochiral aromatic ketones to optically pure alcohols by a coupled enzyme system for cofactor regeneration
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A simple, highly efficient, and economical biphasic cell-free system was developed for biocatalytic reduction of prochiral aromatic ketones to furnish enantiopure alcohols. This system is characterized by using endogenous enzymes of the cell-free extract to form enzyme-coupled NADPH recycling system. Besides, it offered much higher productivity than whole cells and greatly simplified the preparation process of biocatalysts in comparison with isolated enzymes. Various prochiral aromatic ketones, especially α-substituted acetophenone derivatives, were reduced to chiral alcohols with excellent enantiomeric excess (ee) and moderate to good yield by this cell-free system.
- Yan, Zhen,Nie, Yao,Xu, Yan,Liu, Xiang,Xiao, Rong
-
supporting information; experimental part
p. 999 - 1002
(2011/03/21)
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- Novel anti-Prelog stereospecific carbonyl reductases from Candida parapsilosis for asymmetric reduction of prochiral ketones
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The application of biocatalysis to the synthesis of chiral molecules is one of the greenest technologies for the replacement of chemical routes due to its environmentally benign reaction conditions and unparalleled chemo-, regio- and stereoselectivities. We have been interested in searching for carbonyl reductase enzymes and assessing their substrate specificity and stereoselectivity. We now report a gene cluster identified in Candida parapsilosis that consists of four open reading frames including three putative stereospecific carbonyl reductases (scr1, scr2, and scr3) and an alcohol dehydrogenase (cpadh). These newly identified three stereospecific carbonyl reductases (SCRs) showed high catalytic activities for producing (S)-1-phenyl-1,2-ethanediol from 2-hydroxyacetophenone with NADPH as the coenzyme. Together with CPADH, all four enzymes from this cluster are carbonyl reductases with novel anti-Prelog stereoselectivity. SCR1 and SCR3 exhibited distinct specificities to acetophenone derivatives and chloro-substituted 2-hydroxyacetophenones, and especially very high activities towards ethyl 4-chloro-3-oxobutyrate, a β-ketoester with important pharmaceutical potential. Our study also showed that genomic mining is a powerful tool for the discovery of new enzymes.
- Nie, Yao,Xiao, Rong,Xu, Yan,Montelione, Gaetano T.
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experimental part
p. 4070 - 4078
(2011/07/08)
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- One-pot synthesis of enantiomerically pure 1, 2-diols: Asymmetric reduction of aromatic α-oxoaldehydes catalysed by Candida parapsilosis ATCC 7330
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A facile and simple one-pot method was developed to produce a series of optically active (S)-1-phenyl-1,2-ethanediols with good yields (up to 70%) and high enantiomeric excess (>99%) via asymmetric reduction of various substituted aromatic α-oxoaldehydes using Candida parapsilosis ATCC 7330.
- Mahajabeen, Pula,Chadha, Anju
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experimental part
p. 2156 - 2160
(2012/05/04)
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- Access to enantiopure aromatic epoxides and diols using epoxide hydrolases derived from total biofilter DNA
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Metagenomic DNA is a rich source of genes encoding novel epoxide hydrolases (EHs). We retrieved two genes encoding functional EHs from total DNA isolated from biofilter-derived biomass, using PCR with EH-specific degenerate primers followed by genome-walking PCR. The degenerate primers were based on two EH-specific consensus sequences: HGWP and GHDWG. The resulting recombinant EHs, Kau2 and Kau8, were expressed in Escherichia coli, and their enantioselectivity and regioselectivity were determined using 13 different epoxide substrates. The EH Kau2 had broad substrate specificity and preferentially hydrolyzed epoxides with S-configuration. It showed high enantioselectivity towards aromatic epoxides such as styrene oxide, p-nitrostyrene oxide, and trans-1-phenyl-1,2-epoxypropane. In addition, Kau2 showed enantioconvergent hydrolysis activity. The EH Kau8 also showed broad substrate specificity and preferentially hydrolyzed epoxides with R-configuration. High enantioselectivity was observed for p-nitrostyrene oxide, and the hydrolysis activity of Kau8 was less enantioconvergent than that of Kau2. To determine the usefulness of Kau2 for synthetic applications, preparative-scale biohydrolysis reactions were performed. Specifically, two kinetic resolutions were carried out with 80 g/L of racemic trans-1-phenyl-1,2-epoxypropane, affording both (1R,2R)-epoxide and the corresponding (1R,2S)-diol in high enantiomeric excess (>99%) and good yield (>45%). In addition, a process based on enantioconvergent hydrolysis by the EH Kau2 was established for racemic cis-1-phenyl-1,2-epoxypropane at a concentration of 13 g/L, resulting in the formation of the corresponding (1R,2R)-diol with a 97% yield and an enantiomeric excess exceeding 98%.
- Kotik, Michael,Stepanek, Vaclav,Grulich, Michal,Kyslik, Pavel,Archelas, Alain
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experimental part
p. 41 - 48
(2010/12/19)
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- Free and immobilized Aspergillus niger epoxide hydrolase-catalyzed hydrolytic kinetic resolution of racemic p-chlorostyrene oxide in a neat organic solvent medium
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An enantio- and regioselective hydrolytic kinetic resolution (HKR) of racemic p-chlorostyrene oxide (rac-pCSO) was achieved by epoxide hydrolase (EH) from recombinant Aspergillus niger in a selected neat organic solvent medium. The solid free EH was reuse
- Karboune, Salwa,Archelas, Alain,Baratti, Jacques C.
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experimental part
p. 210 - 216
(2011/12/05)
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- Asymmetric dihydroxylation of aryl olefins by sequential enantioselective epoxidation and regioselective hydrolysis with tandem biocatalysts
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Chiral aryl vicinal diols were obtained in high ee and yield by asymmetric dihydroxylation of aryl olefins with tandem biocatalysts: one contains an enantioselective styrene monooxygenase, and the other contains a regioselective epoxide hydrolase.
- Xu, Yi,Jia, Xin,Panke, Sven,Li, Zhi
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supporting information; experimental part
p. 1481 - 1483
(2009/09/06)
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- S-Methylidene agents: preparation of chiral non-racemic heterocycles
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Reaction of sulfur ylide with aldehyde, imine, and ketone functionality affords the desired three-membered heterocycle in excellent yield. The sulfur ylide is generated in situ upon decarboxylation of carboxymethylsulfonium betaine functionality. Of the seven carboxymethylsulfonium betaine derivatives surveyed, the highest level of conversion of π-acceptor to heterocycle was obtained with the one having S-methyl and S-phenyl functionality bound to a thioacetate derivative. Methylene aziridinations and epoxidations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion, and scope. While moderate levels of diastereocontrol were observed in the aziridination of imine functionality, the four oxiranes resolved using Jacobsen's Co(II)-salen complex were obtained in both high yield and enantioselectivity. The isolated chiral non-racemic oxiranes constitute the formal synthesis of chelonin B and combretastatin starting from 3-bromo-4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde, respectively.
- Forbes, David C.,Bettigeri, Sampada V.,Patrawala, Samit A.,Pischek, Susanna C.,Standen, Michael C.
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supporting information; experimental part
p. 70 - 76
(2009/04/06)
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- Enantioconvergent hydrolysis of styrene epoxides by newly discovered epoxide hydrolases in mung bean
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Two novel epoxide hydrolases were discovered in mung bean (Phaseolus radiatus L.) for the first time, either of which can catalyze enantioconvergent hydrolysis of styrene epoxides. Their regioselectivity coefficients are more than 90% for the p-nitrostyrene oxide. Furthermore, the crude mung bean powder was also shown to be a cheap and practical biocatalyst, allowing a one-step asymmetric synthesis of chiral (R)-diols from racemic epoxides, in up to >99% ee and 68.7% overall yield (after recrystallization).
- Xu, Wei,Xu, Jian-He,Pan, Jiang,Gu, Qing,Wu, Xin-Yan
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p. 1737 - 1740
(2007/10/03)
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- Self-assembled nanoreactors as highly active catalysts in the hydrolytic kinetic resolution (HKR) of epoxides in water
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CoIII(salen) complexes have been immobilized on amphiphilic block copolymers, which self-assemble in water to give micellar aggregates with a hydrophobic Co(salen) core and a water-soluble shell (see picture). These aggregates were used to catalyze the hydrolytic kinetic resolution (HKR) of racemic aromatic epoxides over four consecutive cycles and gave the epoxides in up to 99 % ee. H2salen = N,N′-bis(salicylidene)ethylenediamine. (Chemical Equation Presented).
- Rossbach, Benjamin M.,Leopold, Kerstin,Weberskirch, Ralf
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p. 1309 - 1312
(2007/10/03)
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- Enantioselective reaction of α-lithiated thiazolidines as new chiral formyl anion equivalents
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The reaction of lithiated N-Boc-thiazolidine and N-Boc-benzothiazolidine with benzophenone in the presence of (-)-sparteine afforded the products with up to 97% ee and 93% ee, respectively. The reaction with various aromatic and aliphatic aldehydes also afforded the products with high enantioselectivity and moderate diastereoselectivity. Each diastereomer could be converted to optically active diols. Consequently, lithiated N-Boc-thiazolidine and N-Boc-benzothiazolidine serve as chiral formyl anion equivalents. The reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.
- Wang, Libo,Nakamura, Shuichi,Ito, Yuji,Toru, Takeshi
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p. 3059 - 3072
(2007/10/03)
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- FLUORO-METHANESULFONYL-SUBSTITUTED CYCLOALKANOINDOLES AND THEIR USE AS PROSTAGLANDIN D2 ANTAGONISTS
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Novel cycloalkanoindole derivatives of formula (I) are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.
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- Enantioselective reduction of α-keto esters to 1,2-diols using the NaBH4/Me3SiCl system catalyzed by polymer-supported chiral sulfonamide
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In the presence of 25mol% of a polymer-supported chiral sulfonamide, a variety of α-keto esters can be reduced into the corresponding 1,2-diols in good yields and high enantioselectivities using the NaBH4/Me 3SiCl reducing system.
- Wang, Guang-Yin,Hu, Jian-Bing,Zhao, Gang
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p. 807 - 810
(2007/10/03)
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- Enzymatic transformations. Part 58: Enantioconvergent biohydrolysis of styrene oxide derivatives catalysed by the Solanum tuberosum epoxide hydrolase
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The biohydrolysis of four racemic styrene oxide derivatives has been explored, using the (recombinant) Solanum tuberosum epoxide hydrolase. Interestingly, this enzyme showed a marked tendency to operate a so-called enantioconvergent process, thus affording the corresponding (R)-diol in a nearly quantitative yield and good to excellent ee. We have demonstrated that this is due to the fact that the (S)-enantiomer of these epoxides was preferably attacked at the (benzylic) more substituted carbon atom, whereas the (R)-epoxide was attacked at the (terminal) less substituted carbon atom. The thus obtained meta- and para-chlorostyrene diol derivatives are important building blocks in the synthesis of various biologically active molecules. A nine cycles repeated batch reactor was performed starting from racemic meta-chlorostyrene oxide and afforded a 100% analytical yield (88% preparative) of the corresponding diol, obtained with ees as high as 97%.
- Monterde, Maria I.,Lombard, Murielle,Archelas, Alain,Cronin, Annette,Arand, Michael,Furstoss, Roland
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p. 2801 - 2805
(2007/10/03)
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- Enantioselective hydrolysis of various substituted styrene oxides with Aspergillus Niger CGMCC 0496
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Enantioselective biohydrolysis of various substituted styrene oxides using whole fungus cells of Aspergillus niger CGMCC 0496 are described. The results show not only para- but also some ortho- substituted styrene oxides can achieve high enantioselectivity during the hydrolysis.
- Jin, Hao,Li, Zu-Yi,Dong, Xiao-Wei
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p. 408 - 414
(2007/10/03)
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- Chemoenzymatic synthesis of enantiomerically pure terminal 1,2-diols
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A new practical method for the enzymatic synthesis of 1,2-diols has been developed by employing a lipase catalyzed one-pot transesterification protocol. A series of substituted α-acetoxyphenylethanones 3a-g have been reduced to the corresponding alcohols under mild conditions employing sodium borohydride and moist neutral alumina, and further subjected for lipase catalyzed irreversible transesterification in the same pot to give mono- and diacetate diols (R)-4 and (S)-5, which on hydrolysis afforded terminal 1,2-diols, (R)- and (S)-6 in high enantiomeric excess.
- Kamal, Ahmed,Sandbhor, Mahendra,Ahmed, Kaleem,Adil,Shaik, Ahmad Ali
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p. 3861 - 3866
(2007/10/03)
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- Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen)CoIII complexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols
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The hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by chiral (salen)CoIII complex 1·OAc affords both recovered unreacted epoxide and 1,2-diol product in highly enantioenriched form. As such, the HKR provides general access to useful, highly enantioenriched chiral building blocks that are otherwise difficult to access, from inexpensive racemic materials. The reaction has several appealing features from a practical standpoint, including the use of H2O as a reactant and low loadings (0.2-2.0 mol %) of a recyclable, commercially available catalyst. In addition, the HKR displays extraordinary scope, as a wide assortment of sterically and electronically varied epoxides can be resolved to ≥ 99% ee. The corresponding 1,2-diols were produced in good-to-high enantiomeric excess using 0.45 equiv of H2O. Useful and general protocols are provided for the isolation of highly enantioenriched epoxides and diols, as well as for catalyst recovery and recycling. Selectivity factors (krel) were determined for the HKR reactions by measuring the product ee at ca. 20% conversion. In nearly all cases, krel values for the HKR exceed 50, and in several cases are well in excess of 200.
- Schaus, Scott E.,Brandes, Bridget D.,Larrow, Jay F.,Tokunaga, Makoto,Hansen, Karl B.,Gould, Alexandra E.,Furrow, Michael E.,Jacobsen, Eric N.
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p. 1307 - 1315
(2007/10/03)
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- Asymmetric synthesis of 1-aryl-1,2-ethanediols from arylacetylenes by palladium-catalyzed asymmetric hydrosilylation as a key step
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Double hydrosilylation of arylacetylenes with trichlorosilane catalyzed first by platinum and second by a chiral monophosphine-palladium complex generated the corresponding 1,2-bis(silyl)-1-arylethanes, the oxidation of which with hydrogen peroxide gave 1-aryl-1,2-diols of high enantiomeric purity (94-98% ee) in high yields. Copyright
- Shimada, Toyoshi,Mukaide, Kotaro,Shinohara, Akihiro,Han, Jin Wook,Hayashi, Tamio
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p. 1584 - 1585
(2007/10/03)
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- Biocatalytic Potential of the Epoxide Hydrolase from Agrobacterium radiobacter AD1 and a Mutant with Enhanced Enantioselectivity
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Optically pure epoxides are useful synthons for a variety of biologically active compounds. The epoxide hydrolase obtained from Agrobacterium radiobacter AD1 hydrolyses racemic aryl epoxides with moderate and aliphatic epoxides with low enantioselectivity
- Lutje Spelberg, Jeffrey H.,Rink, Rick,Archelas, Alain,Furstoss, Roland,Janssen, Dick B.
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p. 980 - 985
(2007/10/03)
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- Microbiological transformations. Part 45: A green chemistry preparative scale synthesis of enantiopure building blocks of Eliprodil: Elaboration of a high substrate concentration epoxide hydrolase-catalyzed hydrolytic kinetic resolution process
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The enantioselective hydrolysis of racemic para-chlorostyrene oxide 2 following a typical 'green chemistry' procedure based on the use of two different Epoxide Hydrolases is described. This allows the preparation of both enantiomers of 2 in very high enantiomeric purity. Furthermore, using a 'one-pot' sequential bi-enzymatic strategy enabling to overcome the 50% yield limitation intrinsic to any resolution process, rac-2 could be transformed into nearly enantiopure (R)-3 with an overall yield as high as 93%. The methodology developed was based on the use of a biphasic reactor at high substrate concentration, which is highly desirable for any potential industrial process. The obtained chirons are valuable building blocks for the synthesis of various biologically active targets, like (R)-Eliprodil.
- Manoj,Archelas,Baratti,Furstoss
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p. 695 - 701
(2007/10/03)
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- Microbial asymmetric reduction of α-hydroxyketones in the anti-Prelog selectivity
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Yamadazyma farinosa IFO 10896 was found to reduce α-hydroxyketones bearing a phenyl ring to give optically active diols with anti-Prelog selectivity. The distance between the carbonyl group and the phenyl ring was shown to have an interesting effect on the reactivity and selectivity of the enzyme system.
- Tsujigami, Toshikuni,Sugai, Takeshi,Ohta, Hiromichi
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p. 2543 - 2549
(2007/10/03)
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- Stereoselective synthesis of styrene oxides via a Mitsunobu cyclodehydration.
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[reaction: see text] The Mitsunobu cyclodehydration of chiral phenethane-1,2-diols (4), readily accessed from the styrene derivative (5), has been demonstrated to provide the corresponding styrene oxides (2) with high levels of stereoretention (up to 99%). Optimized reaction conditions are described, from which the combination of tricyclohexylphosphine (Chx(3)P) and diisopropylazodicarboxylate (DIAD) in THF and R = EWG provides the best results.
- Weissman,Rossen,Reider
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p. 2513 - 2515
(2007/10/03)
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- Microbial transformation of 2-hydroxy and 2-acetoxy ketones with Geotrichum sp.
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Biotransformation of a series of o-, m- and p-substituted α-hydroxy- and α-acetoxyphenylethanones 1a-h and 9a-g with Geotrichum sp. led to the corresponding 1,2-diols 2 and/or monoacetates 10 in moderate to excellent enantiomeric excesses. α-Hydroxy- and α-acetoxyphenylethanones and their m- and p-derivatives gave preponderantly the S-configuration products while in the case of the o-derivatives R-alcohol was provided as the major enantiomer. The results of stereoselectivity were discussed. (C) 2000 Elsevier Science Ltd.
- Wei, Zhi-Liang,Lin, Guo-Qiang,Li, Zu-Yi
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p. 1129 - 1137
(2007/10/03)
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- Osmium-Catalyzed Dihydroxylation of Olefins Using Dioxygen or Air as the Terminal Oxidant
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The osmium-catalyzed dihydroxylation of various olefins using molecular oxygen or air as the stoichiometric oxidant is reported. Aromatic olefins yield the corresponding diols in good to excellent chemoselectivities under optimized pH conditions (pH = 10.4-12.0). Air can be used under moderate pressures (3-9 bar) instead of dioxygen as the reoxidant. By increasing the oxygen content of the solution, it is possible to achieve highly efficient conversion at low catalyst amount (catalyst/substrate = 1:4000). Tri- and tetrasubstituted olefins are oxidized at pH > 11 to give the corresponding 1,2-diols in good to very good yields without requiring the addition of sulfonamides or other hydrolysis agents. Studies of the dihydroxylation of functionalized olefins demonstrate that the reaction conditions tolerate a variety of functional groups. In the presence of dihydroquinine or dihydroquinidine derivatives (Sharpless ligands), asymmetric dihydroxylations occur with lower enantioselectivities than tose of the classical K3[Fe(CN)6] reoxidation system.
- Doebler, Christian,Mehltretter, Gerald M.,Sundermeier, Uta,Beller, Matthias
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p. 10289 - 10289
(2007/10/03)
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- A practical method for synthesis of terminal 1,2-diols in high enantiomeric excess via oxazaborolidine-catalyzed asymmetric reduction
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Asymmetric borane reduction of α-hydroxy ketones protected with a tetrahydropyranyl (THP) group catalyzed by Corey's CBS reagent using N- phenylamine-borane complexes as the hydride source provided the corresponding terminal 1,2-diols with a very high enantiomeric excess.
- Cho, Byung Tae,Chun, Yu Sung
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p. 1843 - 1846
(2007/10/03)
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- Microbiological Transformations. 38. Clues to the Involvement of a General Acid Activation during Hydrolysis of Para-Substituted Styrene Oxides by a Soluble Epoxide Hydrolase from Syncephalastrum racemosum
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In the course of this work, we have determined the regioselectivity as well as the rate of biohydrolysis of various para-substituted styrene oxide derivatives catalyzed by a new epoxide hydrolase activity found in the soluble cell extract of the fungus Syncephalastrum racemosum. We have observed that this regioselectivity switched progressively from the benzylic Cα carbon atom to the terminal Cβ carbon atom depending upon the electronic character of the para substituent. Hammett plotting of the ratio of water incorporation at both the benzylic and terminal carbon atoms, i.e., log α/β versus σ, gave linear relationships for the two (R)- and (S)-epoxide enantiomers with slopes pα/β = -2.07 and -1.35, respectively. Apparent kinetic constants Km and Vmax were determined for the biohydrolysis of the enantiomers of R absolute configuration, which were the better substrates. Hammett correlation was investigated for Vmax/Km for the reaction on both the Cα and Cβ carbon atoms. Log αVmax/Km vs σ gave a linear relationship with a slope pαvmax/Km = -1.8, suggesting that, in the case of these enzyme/substrate couples, the rate-determining step is the oxirane ring cleavage. These results give, for the first time, interesting clues to the fact that a general acid activation of the epoxide is very probably involved in a concerted process together with its nucleophilic attack.
- Moussou,Archelas,Baratti,Furstoss
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p. 3532 - 3537
(2007/10/03)
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- Microbiological transformations. 33. Fungal epoxide hydrolases applied to the synthesis of enantiopure para-substituted styrene oxides. A mechanistic approach
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The biohydrolysis of differently para-substituted styrene oxide derivatives was studied, using whole cells of the fungi Aspergillus niger or Beauveria sulfurescens. These microorganisms proved to be equipped with epoxide hydrolases which are able to achieve these hydrolyses with high enantioselectivity. This allowed the preparation of the optically active epoxides and of the corresponding vicinal diols which were obtained with good to excellent enantiomeric purity. These two microorganisms proved to be enantiocomplementary. A mechanistic study, carried out using a crude lyophilized enzymatic extract from A. niger, indicated via Hammet coefficient plotting that this hydrolysis is very probably due to a general base-catalyzed process.
- Pedragosa-Moreau,Morisseau,Zylber,Archelas,Baratti,Furstoss
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p. 7402 - 7407
(2007/10/03)
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- Nucleophilic reactions between cyclic 1,2-sulfites and chloride ions
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When cyclic 1,2-sulfites are ring opened by chloride ion, the chlorohydrins are formed with low regio- and stereo-selectivity. The mechanisms involved in the process were investigated by measuring the stereochemical outcome of the reactions. The results showed that reversible inversion pathways (SN2 reactions) and a retention pathway (SN2i reaction) gave rise to the loss in ee in both the chlorohydrins and in the cyclic 1,2-sulfites. Acta Chemica Scandinavica 1996.
- Nymann, Kirsten,Jensen, Linda,Svendsen, John S.
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p. 832 - 841
(2007/10/03)
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- New Diol Metabolites Derived by Biooxidation of Chlorostyrenes with Pseudomonas putida: Determination of Absolute Stereochemistry and Enantiomeric Excess by Convergent Syntheses
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The three isomers of chlorostyrenes were subjected to whole cell biooxidation by means of a mutant strain of Pseudomonas putida 39D.The metabolites were isolated and their absolute stereochemistry determined by conversion to known standards derived from 1-ethenyl-2,3-dihydroxycyclohexa-4,6-diene whose absolute configuration has been previously established.The extent of ring vs side chain oxidation of the chlorostyrene isomers was evaluated and the enantiomeric excess determined for all compounds.
- Hudlicky, Tomas,Boros, Eric E.,Boros, Christie H.
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p. 1365 - 1386
(2007/10/02)
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- Enzymatic Resolution of 1,2-Diols: Comparison between Hydrolysis and Transesterification Reactions
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A new practical procedure for the enzymatic resolution of 1,2-diols 1a-e has been developed by lipase-catalysed regio- and enantio-selective esterification using anhydrides as acylating agents in organic solvents.
- Bosetti, Aldo,Bianchi, Daniele,Cesti, Pietro,Golini, Paolo,Spezia, Sandro
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p. 2395 - 2398
(2007/10/02)
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