- Unmasking the Hidden Carbonyl Group Using Gold(I) Catalysts and Alcohol Dehydrogenases: Design of a Thermodynamically-Driven Cascade toward Optically Active Halohydrins
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A concurrent cascade combining the use of a gold(I) N-heterocyclic carbene (NHC) and an alcohol dehydrogenase (ADH) is disclosed for the synthesis of highly valuable enantiopure halohydrins in an aqueous medium and under mild reaction conditions. The meth
- Escot, Lorena,González-Granda, Sergio,Gotor-Fernández, Vicente,Lavandera, Iván
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p. 2552 - 2560
(2022/02/16)
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- Chiral salen - Ni (II) based spherical porous silica as platform for asymmetric transfer hydrogenation reaction and synthesis of potent drug intermediate montekulast
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Heterogeneous catalyst has an edge over homogeneous systems in terms of recyclability, activity, stability and recovery. Silica has evolved as a good support material in heterogeneous systems due to its stability and ability to get modified as per the end application. Herein, we report a novel chiral Ni-Schiff base derived catalyst and its immobilization into mesoporous silica which was synthesized by post-grafting process. The chiral catalyst demonstrated remarkably high catalytic activity, enantioselectivity (up to 99 % enantiomers excess) for heterogeneous asymmetric transfer hydrogenation of various ketones. The developed catalyst was characterized by Ultraviolet-visible spectroscopy (UV–vis), Fourier-Transform Infrared spectroscopy (FT-IR), X-ray Powder Diffraction (XRD), Brunauer-Emmett-Teller (BET isotherm), Scanning Electron Microscopy – Energy Dispersive X-ray Spectroscopy (SEM-EDX), High Resolution – Transmission Electron Microscopy (HR-TEM), Vibrating Sample Magnetometer (VSM), X-ray Photoelectron Spectroscopy (XPS) and elemental analysis. The catalyst could be recovered and reused for multiple consecutive runs without losing the enantioselectivity. The chiral catalyst was used in asymmetric transfer hydrogenation reaction for synthesizing enantiomerically pure drug intermediate Montekulast.
- Shukla, Meenakshi,Barick,Salunke,Chandra, Sudeshna
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- Chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols
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In this study, chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols was achieved with high selectivity. Irrespective of the electronic nature and the substitution patterns on the aromatic rings, a variety of substrates were suitable for this reaction. The branched acyl component was considered to be optimal for obtaining high s-values. The transition state of the reaction was proposed based on the absolute configuration of the obtained product.
- Sawada, Erika,Nakata, Kenya
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p. 371 - 373
(2021/03/16)
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- Supported ionic liquid-like phases as efficient solid ionic solvents for the immobilisation of alcohol dehydrogenases towards the development of stereoselective bioreductions
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Polymeric materials containing ionic liquid fragments, like those found in bulk ILs, are excellent solid media for the immobilisation of biocatalysts. Herein, the entrapment of the enzymatic system formed by alcohol dehydrogenase from Rhodococcus ruber (ADH-A) overexpressed in E. coli and its coenzyme has been studied. The activity, stability and reusability of these preparations have been investigated in the bioreduction of prochiral ketones finding excellent levels of conversion and selectivity. Interestingly, the immobilised enzyme remained active and exhibited excellent stability in aqueous solutions after several recycling uses. More importantly, these biopolymer materials retained most of their activity after consecutive reaction cycles, prolonged storage and under flow conditions.
- Altava, Belen,García-Verdugo, Eduardo,Gotor-Fernández, Vicente,Lavandera, Iván,Lozano, Pedro,Luis, Santiago V.,Porcar, Raul
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p. 5609 - 5617
(2021/08/16)
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- Asymmetric Catalytic Meerwein-Ponndorf-Verley Reduction of Ketones with Aluminum(III)-VANOL Catalysts
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We report herein an efficient aluminum-catalyzed asymmetric MPV reduction of ketones with broad substrate scope and excellent yields and enantiomeric inductions. A variety of aromatic (both electron-poor and electron-rich) and aliphatic ketones were converted to chiral alcohols in good yields with high enantioselectivities (26 examples, 70-98percent yield and 82-99percent ee). This method operates under mild conditions (-10 °C) and low catalyst loading (1-5 mol percent). Furthermore, this process is catalyzed by the earth-abundant main-group element aluminum and employs 2-propanol as the hydride source.
- Guan, Yong,Mohammadlou, Aliakbar,Staples, Richard,Sullivan, Ryan P.,Wulff, William D.,Yin, Xiaopeng,Zheng, Li
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p. 7188 - 7194
(2020/07/21)
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- Characterization of a robust glucose 1-dehydrogenase, SyGDH, and its application in NADPH regeneration for the asymmetric reduction of haloketone by a carbonyl reductase in organic solvent/buffer system
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To realize coenzyme regeneration in the reduction of haloketones, a codon-optimized gene Sygdh encoding glucose 1-dehydrogenase (SyGDH) was synthesized based on the putative GDH gene sequence (Ta0897) in Thermoplasma acidophilum genomic DNA, and expressed in E. coli BL21(DE3). Recombinant SyGDH was purified to homogeneity by affinity chromatography with the specific activity of 86.3 U/mg protein towards D-glucose at the optimum pH and temperature of 7.5 and 40 °C. It was highly stable in a pH range of 4.5–8.0 and at 60 °C or below, and resistant to various organic solvents. The Km and catalytic efficiency (kcat/Km) of SyGDH towards NADP+ were 0.67 mM and 104.0 mM?1 s?1, respectively, while those towards NAD+ were 157.9 mM and 0.64 mM?1 s?1, suggesting that it preferred NADP+ as coenzyme to NAD+. Additionally, using whole cells of E. coli/Sygdh-Sys1, coexpressing SyGDH and carbonyl reductase (SyS1), as the biocatalyst, the asymmetric reduction of 60 mM m-chlorophenacyl chloride coupled with the regeneration of NADPH in situ was conducted in DMSO/phosphate buffer (2:8, v/v) system, producing (R)-2-chloro-1-(3-chlorophenyl)ethanol with over 99.9% eep and 99.2% yield. Similarly, the reduction of 40 mM α-bromoacetophenone in n-hexane/buffer (6:4, v/v) biphasic system produced (S)-2-bromo-1-phenylethanol with over 99.9% eep and 98.3% yield.
- Hu, Die,Wen, Zheng,Li, Chuang,Hu, Bochun,Zhang, Ting,Li, Jianfang,Wu, Minchen
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- Lipase mediated enzymatic kinetic resolution of phenylethyl halohydrins acetates: A case of study and rationalization
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Racemic phenylethyl halohydrins acetates containing several groups attached to the aromatic ring were resolved via hydrolysis reaction in the presence of lipase B from Candida antarctica (Novozym 435). In all cases, the kinetic resolution was highly selective (E > 200) leading to the corresponding (S)-β-halohydrin with ee > 99 %. However, the time required for an ideal 50 % conversion ranged from 15 min for 2,4-dichlorophenyl chlorohydrin acetate to 216 h for 2-chlorophenyl bromohydrin acetate. Six chlorohydrins and five bromohydrins were evaluated, the latter being less reactive. For the β-brominated substrates, steric hindrance on the aromatic ring played a crucial role, which was not observed for the β-chlorinated derivatives. To shed light on the different reaction rates, docking studies were carried out with all the substrates using MD simulations. The computational data obtained for the β-brominated substrates, based on the parameters analysed such as NAC (near attack conformation), distance between Ser-O and carbonyl-C and oxyanion site stabilization were in agreement with the experimental results. On the other hand, the data obtained for β-chlorinated substrates suggested that physical aspects such as high hydrophobicity or induced change in the conformation of the enzymatic active site are more relevant aspects when compared to steric hindrance effects.
- Fonseca, Thiago de Sousa,Vega, Kimberly Benedetti,da Silva, Marcos Reinaldo,de Oliveira, Maria da Concei??o Ferreira,de Lemos, Telma Leda Gomes,Contente, Martina Letizia,Molinari, Francesco,Cespugli, Marco,Fortuna, Sara,Gardossi, Lucia,de Mattos, Marcos Carlos
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- Asymmetric synthesis of α-bromohydrins by carrot root as biocatalyst and conversion to enantiopure β-hydroxytriazoles and styrene oxides using click chemistry and SN2 ring-closure
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In this study we have combined the bioreduction of α-bromoketones using carrot root as biocatalyst and click chemistry for the preparation of enantiopure β-hydroxytriazoles in excellent enantiomeric excesses and yields. Moreover, we have utilized chiral α-halohydrins for the synthesis of enantiopure styrene oxides in very good yields and enantiomeric excesses. Structural assignments of the products were based on their 1H and 13C NMR data and their optical rotations. The enantiomeric excess of the chiral products was obtained by HPLC analysis.
- Hosseinzadeh, Rahman,Mohadjerani, Maryam,Mesgar, Sakineh
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p. 583 - 591
(2019/02/17)
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- Asymmetric transfer hydrogenation of ketones using Ru(0) nanoparticles modified by Chiral Thiones
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The catalytic asymmetric transfer hydrogenation (ATH) of acetophenone in isopropanol by Ru(0) nanoparticles (NPs) obtained by the in-situ reduction of Ru (II) half-sandwich complexes of chiral 2-oxazolidinethiones and 2-thiozolidinethiones was examined and compared with the catalytic activity of Ru(0) NPs formed in-situ by the reduction of [Ru(p-cymene)(Cl)2]2 in presence of optically active ligands such as (S)-4-isobutylthiazolidine-2-thione, (S)-4-Isopropyl-2(?2-pyridinyl)-2-oxazoline, (8S, 9R)-(?)-cinchonidine, (S)-leucinol, (S)-phenylalaninol, and (S)-leucine. Three of the best catalytic systems were then examined for ATH of thirteen aromatic ketones with different electronic and steric properties. A maximum of 24% ee was obtained using NPs generated from the Ru (II) half-sandwich complex with (S)-4-isobutylthiazolidine-2-thione in the TH of acetophenone. The NPs were characterized by TEM and DLS measurements. Kinetic studies and poisoning experiments confirmed that the reaction is catalyzed by the chiral NPs formed in-situ. Complete characterization of the complexes, including the X-ray crystallographic characterization of two complexes, was also carried out.
- Din Reshi, Noor U.,Senthurpandi, Dineshchakravarthy,Samuelson, Ashoka G.
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- Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity
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The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.
- Shanati, Tarek,Lockie, Cameron,Beloti, Lilian,Grogan, Gideon,Ansorge-Schumacher, Marion B.
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p. 6202 - 6211
(2019/08/15)
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- Exploring the Biocatalytic Scope of a Novel Enantioselective Halohydrin Dehalogenase from an Alphaproteobacterium
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A gene encoding halohydrin dehalogenase from an alphaproteobacterium (AbHHDH) was identified, cloned and over-expressed in Escherichia coli. AbHHDH was able to catalyze the stereoselective dehalogenation of prochiral and racemic halohydrins. It showed the highest enantioselectivity in the dehalogenation of 20?mM (R,S)-2-bromo-1-phenylethanol, which yielded (S)-2-bromo-1-phenylethanol with 99% ee and 34.5% yield. Moreover, AbHHDH catalyzed the azidolysis of epoxides with low to moderate (S)-enantioselectivity. The highest enantioselectivity (E = 18.6) was observed when (R,S)-benzyl glycidyl ether was used as the substrate. A sequential kinetic resolution catalyzed by HHDH was employed for the synthesis of chiral 1-chloro-3-phenoxy-2-propanol. We prepared enantiopure (S)-isomer with a high enantiopurity of ee > 99% and a yield of 30.7% (E-value: 21.3) by kinetic resolution of 20?mM substrate. The (S)-isomer with 99% ee readily obtained from 40 to 150?mM (R,S)-1-chloro-3-phenoxy-2-propanol. Taken together, the results of this study demonstrate the applicability of this HHDH for the production of optically active compounds. [Figure not available: see fulltext.].
- Xue, Feng,Ya, Xiangju,Xiu, Yuansong,Tong, Qi,Wang, Yuqi,Zhu, Xinhai,Huang, He
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p. 629 - 637
(2019/01/25)
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- Cascade bio-hydroxylation and dehalogenation for one-pot enantioselective synthesis of optically active β-halohydrins from halohydrocarbons
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A stereoselective hydroxylation and enantioselective dehalogenation cascade reaction was developed for the synthesis of optically active β-haloalcohols from halohydrocarbons. This cascade system employed P450 and halohydrin dehalogenase as two compatible biocatalysts, allowing a straightforward, greener and efficient access to β-halohydrins with excellent enantioselectivities (98-99%).
- Cui, Hai-Bo,Xie, Ling-Zhi,Wan, Nan-Wei,He, Qing,Li, Zhi,Chen, Yong-Zheng
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supporting information
p. 4324 - 4328
(2019/08/21)
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- Iridium-Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins
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Iridium-catalyzed asymmetric hydrogenation of prochiral halogenated ketones was successfully developed to prepare various chiral halohydrins with high reactivities and excellent enantioselectivities under basic reaction condition (up to >99% conversion, 99% yield, >99% ee). Moreover, gram-scale experiment was performed well in the presence of just 0.005 mol% (S/C=20 000) Ir/f-amphox catalyst with 99% yield and >99% ee. (Figure presented.).
- Yin, Congcong,Wu, Weilong,Hu, Yang,Tan, Xuefeng,You, Cai,Liu, Yuanhua,Chen, Ziyi,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 2119 - 2124
(2018/04/30)
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- Molecular Basis for the High Activity and Enantioselectivity of the Carbonyl Reductase from Sporobolomyces salmonicolor toward α-Haloacetophenones
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In an effort to develop a practical method for the synthesis of optically pure 2,2,2-trifluoro-1-phenylethanol, we found that the carbonyl reductase (SSCR) from Sporobolomyces salmonicolor showed excellent activity and enantioselectivity toward the halogenated acetophenones. Especially, SSCR exhibited more than 1000 times higher activity toward α,α,α-trifluoroacetophenone than unsubstituted acetophenone, a strikingly different observation from the previously well-studied alcohol dehydrogenase (LBADH) from Lactobacillus brevis. Enzyme-substrate docking and site-directed mutagenesis studies revealed the molecular basis for the high enzyme activity and enantioselectivity of SSCR toward the α-halogenated acetophenones. The hydrogen bond of the Asn207 side chain with the substrate halogen atom and the XH/π interaction of the substrate phenyl group with the side chains of Ser222/Thr223 resulted in the formation of the highly reactive conformation of α-halogenated acetophenones in the active site of the enzyme. (S)-2,2,2-Trifluoro-1-phenylethanol was prepared in excellent isolated yield and enantiomeric excess from the reduction of α,α,α-trifluoroacetophenone with mutant T209A. These results suggest that tuning the interactions between the halogen atoms/phenyl group of the substrate and the amino acid residues of the enzyme would lead to valuable mutants for the practical synthesis of β-haloalcohols.
- Chen, Xi,Zhang, Hongliu,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
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p. 3525 - 3531
(2018/04/14)
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- Immobilized and free cells of geotrichum candidum for asymmetric reduction of ketones: Stability and recyclability
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Marine-derived fungus Geotrichum candidum AS 2.361 was previously reported by our group as an active strain for the enantioselective reduction of ketones. Although some other Geotrichum strains were also found from the terrestrial sources, information on their stability and reusability is scarce. Herein, the stabilities—in terms of pH tolerance, thermostability, and storage stability, and reusability—of G. candidum AS 2.361 were described for the asymmetric reduction of a series of aromatic ketones. Two differently immobilized cells (agar immobilization and calcium alginate immobilization) as well as free cells were prepared. For three substrates (1-(3-bromophenyl) ethan-1-one (1b), 1-(2-chlorophenyl) ethan-1-one (1d), and acetophenone (1g)) immobilized cells on agar showed a great improvement in the bioreduction activities compared to the free cells, increasing yields up to 97% with ee values of 99%. Cells immobilized on agar/calcium alginate could maintain more than 90% of the original activities within the assayed pH ranges of 3.5–11, while free cells were highly sensitive to alkaline and acidic conditions. Concerning thermostability, immobilized cells on agar kept 99% of their original activities after incubation at 60?C for 1 h, while almost no activity was detected for the free cells under the same condition. Immobilized cells were stable at 4?C for 80 days without any activity loss, while free cells started to decrease the activity after storage at 4?C for six days. The immobilized cells retained almost 99% activity after four reuse cycles, while free cells lost almost all the activities at on the third cycle.
- Liu, Hui,de Souza, Fayene Zeferino Ribeiro,Liu, Lan,Chen, Bi-Shuang
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- OsXCl(phosphine)2(diamine) and OsXCl(diphosphine)(diamine) (X = Cl, H) Complexes for Ketone Hydrogenation
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The osmium complex trans-[OsCl2(PPh3)2(en)] (2) was prepared by reaction of [OsCl2(PPh3)3] (1a) with ethylenediamine (en), whereas the diphosphine derivatives trans-[OsCl2(dppf)(NN)] (NN = en (3), bn (4; bn = 1,4-butanediamine)) and trans-[OsCl2(dpbp)(en)] (5) were obtained from 1a, dppf or dpbp, and the corresponding NN ligand in CH2Cl2 or toluene. An X-ray diffraction study has been provided for 3. The isolation of the chiral derivatives trans-[OsCl2(diphosphine)((R,R)-dpen)] (diphosphine = dppf (6), dpbp (7), (R,R)-skewphos (8)) was achieved by reacting 1a with the diphosphine and (R,R)-dpen in toluene. Treatment of the precursor [Os2Cl4(P(m-tolyl)3)5] (1b) with en afforded [OsCl2(P(m-tolyl)3)2(en)] (9), while reaction of 1b with dppb and N,N-dmen gave [OsCl2(dppb)(N,N-dmen)] (10). The chiral derivatives [OsCl2(diphosphine)(NN)] (11-21; diphosphine = (S)-MeObiphep, (R)-MeObiphep, (R)-xylMeObiphep, (R)-binap, (S)-xylbinap, (R)-xylbinap, (R,S)-Josiphos NN = en, (R,R)-dpen, (R)-daipen, (R,R)-dppn) were prepared from 1b and the corresponding diphosphine and NN ligands in toluene. The monohydride trans-[OsHCl(P(m-tolyl)3)2(en)] (22) was synthesized by reaction of 1b with H2 (1 atm) in the presence of NEt3, followed by addition of en in toluene. Similarly, trans-[OsHCl(dppf)(en)] (23) was synthesized from 1a, H2, and NEt3, followed by treatment with dppf and en. Complexes 2-5, 9, 10, 22, and 23 efficiently catalyzed the hydrogenation of acetophenone with H2 under low pressure (5 atm) at 60-70 °C in ethanol (1-2 mol % of NaOEt) with the ratio S/C = 5000-10000. The chiral derivatives 6-8 and 11-21 afforded the asymmetric hydrogenation of acetophenone with up to 90% ee by combining bulky xylyl-substituted MeObiphep or binap-type ligands with (R)-daipen or (R,R)-dpen ligands. Catalytic transfer hydrogenation of acetophenone was observed with 3, 6, and 7 (S/C = 2000) in 2-propanol and in the presence of NaOiPr (2 mol %) at 60-82 °C.
- Barbato, Cinzia,Baldino, Salvatore,Ballico, Maurizio,Figliolia, Rosario,Magnolia, Santo,Siega, Katia,Herdtweck, Eberhardt,Strazzolini, Paolo,Chelucci, Giorgio,Baratta, Walter
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- Selective Asymmetric Transfer Hydrogenation of α-Substituted Acetophenones with Bifunctional Oxo-Tethered Ruthenium(II) Catalysts
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A practical method for the asymmetric transfer hydrogenation of α-substituted ketones was developed utilizing oxo-tethered N-sulfonyldiamine-ruthenium complexes. Reduction by HCO2H and HCO2K in a mixed solvent of EtOAc/H2O allowed for the selective synthesis of halohydrins from 2-bromoacetophenone (98%) and 2-chloroacetophenone (>99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO2H and Et3N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of α-sulfonated ketones without eroding the leaving group. (Figure presented.).
- Yuki, Yamato,Touge, Taichiro,Nara, Hideki,Matsumura, Kazuhiko,Fujiwhara, Mitsuhiko,Kayaki, Yoshihito,Ikariya, Takao
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supporting information
p. 568 - 574
(2017/12/13)
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- Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of enantiopure aromatic alcohols
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Enzymatic synthesis of enantiopure aromatic secondary alcohols (including substituted, hetero-aromatic and bicyclic structures) was carried out using halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This enzyme showed an unprecedented substrate scope and absolute enatioselectivity. The cofactor NADPH was used catalytically and regenerated in situ by the biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the conversion of aromatic ketones was markedly influenced by the steric and electronic factors as well as the solubility of ketones in the reaction medium. Furthermore, carbonyl stretching band frequencies ν (CO) have been measured for different ketones to understand the effect of electron withdrawing or donating properties of the ketone substituents on the reaction rate catalyzed by HvADH2. Good correlation was observed between ν (CO) of methyl aryl-ketones and the reaction rate catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.
- Alsafadi, Diya,Alsalman, Safaa,Paradisi, Francesca
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p. 9169 - 9175
(2017/11/15)
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- Catalytic asymmetric Meerwein-Ponndorf-Verley reduction of glyoxylates induced by a chiral N,N′-dioxide/Y(OTf)3 complex
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An asymmetric Meerwein-Ponndorf-Verley (MPV) reduction of glyoxylates was for the first time accomplished via an N,N′-dioxide/Y(OTf)3 complex with aluminium alkoxide and molecular sieves (MSs) as crucial additives. A variety of optically active α-hydroxyesters were obtained with excellent results. A possible reaction mechanism was proposed based on the experiments.
- Wu, Wangbin,Zou, Sijia,Lin, Lili,Ji, Jie,Zhang, Yuheng,Ma, Baiwei,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 3232 - 3235
(2017/03/20)
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- Immobilization of Amano lipase from Pseudomonas fluorescens on silk fibroin spheres: an alternative protocol for the enantioselective synthesis of halohydrins
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The search for a new, efficient, cheaper and sustainable matrix for lipase immobilization is a growing area in biotechnology. Amano lipase from Pseudomonas fluorescens was immobilized on silk fibroin spheres and used in the enzymatic kinetic resolution of halohydrins, to obtain optically active epoxides (up to 99% ee), important precursors in the synthesis of derivative antifungal azoles. This paper reinforces the versatility of silk fibroin as a support for heterogeneous catalysts.
- Ferreira, Irlon M.,Yoshioka, Sergio A.,Comasseto, Jo?o V.,Porto, André L. M.
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p. 12650 - 12658
(2017/03/11)
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- One-pot synthesis of optically pure β-hydroxy sulfones: Via a heterogeneous ruthenium/diamine-promoted nucleophilic substitution-asymmetric transfer hydrogenation tandem process
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A mesoporous silica-based ruthenium/diamine-functionalized heterogeneous catalyst is prepared through the co-condensation of chiral 4-((trimethoxysilyl)ethyl)phenylsulfonyl-1,2-diphenylethylene-diamine and tetraethoxysilane, followed by complexation with a ruthenium/diamine complex. Its solid-state carbon cross-polarization/magic angle spinning NMR spectrum demonstrates well-defined single-site ruthenium/diamine species, whereas the scanning and transmission electron microscopy images confirm the highly distributed ruthenium active centers on uniformly mesostructured nanoparticles. This heterogenous catalyst displays high catalytic and enantioselective performance in the nucleophilic substitution-asymmetric transfer hydrogenation one-pot enantioselective tandem reactions of α-bromoketones and sodium sulfonates, resulting in various chiral β-hydroxy sulfones with up to 99% enantioselectivity. Furthermore, the recycled heterogeneous catalyst can be reused repeatedly for at least six times, providing a practical approach for the one-pot preparation of chiral β-hydroxy sulfones in an environmentally friendly medium.
- Wang, Jinyu,Wu, Liang,Hu, Xiaoying,Liu, Rui,Jin, Ronghua,Liu, Guohua
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p. 4444 - 4450
(2017/10/13)
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- Integration of multiple active sites on large-pore mesoporous silica for enantioselective tandem reactions
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Facile construction of a multifunctional heterogeneous catalyst through the assembly of Au/carbene and chiral ruthenium/diamine dual complexes in large-pore mesoporous silica was developed. This enables an efficient one-pot hydration-asymmetric transfer hydrogenation enantioselective tandem reaction of haloalkynes, affording chiral halohydrins with up to 99% enantioselectivity. Combined multifunctionalities, such as substrate-promoted silanol-functionality, BF4? anion-bonding gold/carbene and covalent-bonding chiral ruthenium/diamine active centers, contributed cooperatively to the catalytic performance.
- Xia, Xuelin,Meng, Jingjing,Wu, Hanxin,Cheng, Tanyu,Liu, Guohua
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supporting information
p. 1638 - 1641
(2017/02/10)
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- Transfer hydrogenation reactions catalyzed by chiral half-sandwich Ruthenium complexes derived from Proline
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Chiral ruthenium half-sandwich complexes were prepared using a chelating diamine made from proline with a phenyl, ethyl, or benzyl group, instead of hydrogen on one of the coordinating arms. Three of these complexes were obtained as single diastereoisomers and their configuration identified by X-ray crystallography. The complexes are recyclable catalysts for the reduction of ketones to chiral alcohols in water. A ruthenium hydride species is identified as the active species by NMR spectroscopy and isotopic labelling experiments. Maximum enantio-selectivity was attained when a phenyl group was directly attached to the primary amine on the diamine ligand derived from proline. [Figure not available: see fulltext.]
- Pandia Kumar, Arun Kumar,Samuelson, Ashoka G
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p. 1405 - 1415
(2016/09/19)
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- Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water
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A practical and convenient method for the efficient and regio- and stereoselective ring-opening of enantiopure monosubstituted epoxides by sodium azide under hydrolytic conditions is reported. The ring-opening of enantiopure styryl and pyridyl (S)-epoxides by N3- in hot water takes place preferentially at the internal position with complete inversion of configuration to produce (R)-2-azido ethanols with up to 99% enantio- and regioselectivity, while the (S)-adamantyl oxirane provides mainly the (S)-1-adamantyl-2-azido ethanol in excellent yield. In general, 1,2-amino ethanols were obtained in high yield and excellent enantiopurity by the reduction of the chiral 1,2-azido ethanols with PPh3 in water/THF, and then converted into the Boc or acetamide derivatives.
- Wang, Hai-Yang,Huang, Kun,De Jesús, Melvin,Espinosa, Sandraliz,Pi?ero-Santiago, Luis E.,Barnes, Charles L.,Ortiz-Marciales, Margarita
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- An imidazolium-modified chiral rhodium/diamine-functionalized periodic mesoporous organosilica for asymmetric transfer hydrogenation of α-haloketones and benzils in aqueous medium
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The use of a hydrophobic, imidazolium-functionalized periodic mesoporous organosilica for immobilization of chiral organometallic complexes as a heterogeneous catalyst is highly desirable as this catalyst can greatly promote an aqueous organic transformation due to its hydrophobic function and phase-transfer feature in an aqueous medium. Herein, by utilizing a three-component co-condensation strategy, we conveniently incorporate 1,2-bis(triethoxysilyl)ethane, (R,R)-4-((trimethoxysilyl)ethyl)phenylsulfonyl-1,2-diphenylethylene-diamine and 1,3-bis(3-(triethoxysilyl)propyl)-1H-imidazol-3-ium iodide within its silicate network, which is coordinated with (Cp?RhCl2)2, leading to an imidazolium-modified chiral rhodium/diamine-functionalized periodic mesoporous organosilica. A solid-state carbon spectrum discloses its well-defined chiral rhodium/diamine active species, and its X-ray diffraction; nitrogen adsorption-desorption measurement and transmission electron microscopy images reveal its ordered dimensional-hexagonal mesostructure. As a bifunctional heterogeneous catalyst, this periodic mesoporous organosilica significantly boosts asymmetric transfer hydrogenation of α-haloketones and benzils in water, where the hydrophobic periodic mesoporous organosilica, phase-transfer-featured imidazolium-functionality, and the confined chiral organorhodium catalytic nature are responsible for its catalytic performance. Furthermore, the catalyst can be recovered and recycled seven times without the loss of its catalytic activity, making it an attractive heterogeneous catalyst for asymmetric transfer hydrogenation in an environmentally friendly manner.
- Zhou, Feng,Hu, Xiaoying,Gao, Ming,Cheng, Tanyu,Liu, Guohua
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p. 5651 - 5657
(2016/10/21)
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- A preparation method of the compound hydroxy bromine
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The present invention discloses a hydroxyl bromine compound preparation method comprising the following steps: in the presence of a catalyst, a compound shown as the formula I and N-brombenzamide are reacted in a liquid mixture of an organic solvent and water to obtain a compound shown as the formula II, wherein R1 are hydrogen or C1-C3 alkyl group; R2 are hydrogen or C1-C3 alkyl group; and R3 are hydrogen or C1-C4 alkyl group. A styrene type substrate and the N-brombenzamide are used as raw materials for effectively synthesizing a series of hydroxyl bromine compounds in the effect of (DHQD) 2PHAL. The raw materials are simple and easy to get, the nucleophile water is non-toxic and harmless, reaction conditions are mild, operation is simple, the method is atomic economic, enantiomer excess can reach up to 88%, the yield can reach up to 94%, the compounds has regioselectivity completely different from that of epoxy ring opening products, meanwhile the introduced C-Br bond and C-O bond both can be further transformed, and the method has great value.
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Paragraph 0024; 0045-0047
(2018/02/04)
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- Preparation of enantiomerically enriched aromatic β-hydroxynitriles and halohydrins by ketone reduction with recombinant ketoreductase KRED1-Pglu
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A NADPH-dependent benzil reductase (KRED1-Pglu) was used as recombinant enzyme for catalysing the reduction of different functionalised ketones. The reactions were carried out in the presence of a catalytic amount of NADP+and an enzyme-coupled transformation (oxidation of glucose catalysed by glucose dehydrogenase), for regenerating the cofactor and thus driving the reaction to completion. KRED1-Pglu showed remarkable versatility, being able to reduce different β-ketonitriles and α-haloketones at different pHs; notably, depending on the nature of the substrate, KRED1-Pglu can be used for efficient and clean enzymatic reduction, avoiding side-reactions due to the pH of the medium. The reduction generally occurred with high enantioselectivity, allowing the preparation of enantiomerically enriched β-hydroxynitriles and halohydrins in high yields; the stereochemical outcome of the reduction followed in all the cases the so-called Prelog's rule.
- Contente, Martina L.,Serra, Immacolata,Molinari, Francesco,Gandolfi, Raffaella,Pinto, Andrea,Romano, Diego
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p. 3974 - 3979
(2016/07/06)
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- Chiral polyethers derived from BINOL and ECH as highly enantioselective and efficient catalysts for the borane reduction of prochiral ketones
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Two novel polyethers derived from BINOL were synthesized and used to induce the enantioselective borane reduction of prochiral ketones. The polyethers gave the expected secondary alcohols with up to 98% yields and over 99% ee values. The recovered polyethers could be reused for many times to induce the enantioselective reduction of prochiral ketones without losing their enantioselective induction ability.
- Zhang, An-Lin,Yu, Zeng-Da,Yang, Li-Wen,Yang, Nian-Fa,Peng, Dan
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p. 407 - 412
(2015/01/30)
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- One-Pot cascade hydration-asymmetric transfer hydrogenation as a practical strategy to construct chiral β-adrenergic receptor blockers
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The facile construction of biologically active β-adrenergic receptor agonists/blockers and analogues is a great fundamental and practical challenge in medical chemistry. Herein, we report a hydration-asymmetric transfer hydrogenation cascade to realize the one-pot enantioselective transformation of aromatic haloalkynes into chiral aromatic halohydrins, which can be converted readily into chiral β-adrenergicreceptor blockers. Such a one-pot cascade process involves the Au-catalyzed hydration of aryl-substituted haloalkynes to aryl-substituted α-halomethyl ketones and the Ru-catalyzed asymmetric transfer hydrogenation of aryl-substituted α-halomethyl ketones to aryl-substituted 2-haloethanols. The significant benefits of this procedure are that it provides chiral aromatic halohydrins in high yields, with excellent enantioselectivities, and a wide variety of functional groups are tolerated under mild conditions. The study described herein offers a useful approach to construct chiral β-adrenergic blockers, which is an attractive practical organic transformation that is performed in a one-pot manner.
- Ye, Qunqun,Cheng, Tanyu,Zhao, Yuxi,Zhao, Junwei,Jin, Ronghua,Liu, Guohua
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p. 1801 - 1805
(2015/06/23)
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- Catalytic Asymmetric Bromination of Unfunctionalized Olefins with H2O as a Nucleophile
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The dimeric cinchona alkaloid (DHQD)2PHAL is used to catalyze an effective asymmetric bromohydroxylation of unfunctionalized olefins with H2O as nucleophile an N-bromobenzamide as a bromine source. A variety of optically active bromohydrins are formed with up to 88%ee. PHAL's positive: An effective asymmetric bromohydroxylation of unfunctionalized olefins with H2O as nucleophile catalyzed by the dimeric cinchona alkaloid (DHQD)2PHAL (see scheme) is described. Optically active bromohydrins are obtained with up to 88%ee.
- Zhang, Xun,Li, Jing,Tian, Hua,Shi, Yian
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p. 11658 - 11663
(2015/08/18)
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- Chiral terpene auxiliaries III: Spiroborate esters from (1R,2S,3R,5R)-3-amino-apopinan-2-ol as highly effective catalysts for asymmetric reduction of ketones with borane
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New spiroborate esters, derived from terpene amino alcohols, (S)-prolinol, and 2-aminoethanol, were employed as catalysts in the borane reduction of acetophenone and other aryl alkyl and halogenated ketones. The corresponding alcohols were obtained in high yields and with enantioselectivities up to 98% ee. The influence of the amino alcohol and the diol moieties of spiroborate on the reaction selectivity was examined. The catalyst load, the nature of the solvent, the borane source, and the reaction conditions were also investigated.
- ?wiklińska, Marta,Krzemiński, Marek P.,Tafelska-Kaczmarek, Agnieszka
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p. 1453 - 1458
(2015/12/09)
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- Steric vs. electronic effects in the Lactobacillus brevis ADH-catalyzed bioreduction of ketones
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Lactobacillus brevis ADH (LBADH) is an alcohol dehydrogenase that is commonly employed to reduce alkyl or aryl ketones usually bearing a methyl, an ethyl or a chloromethyl as a small ketone substituent to the corresponding (R)-alcohols. Herein we have tested a series of 24 acetophenone derivatives differing in their size and electronic properties for their reduction employing LBADH. After plotting the relative activity against the measured substrate volumes we observed that apart from the substrate size other effects must be responsible for the activity obtained. Compared to acetophenone (100% relative activity), other small substrates such as propiophenone, α,α, α-trifluoroacetophenone, α-hydroxyacetophenone, and benzoylacetonitrile had relative activities lower than 30%, while medium-sized ketones such as α-bromo-, α,α-dichloro-, and α,α-dibromoacetophenone presented relative activities between 70% and 550%. Moreover, the comparison between the enzymatic activity and the obtained final conversions using an excess or just 2.5 equiv. of the hydrogen donor 2-propanol, denoted again deviations between them. These data supported that these hydrogen transfer (HT) transformations are mainly thermodynamically controlled. For instance, bulky α-halogenated derivatives could be quantitatively reduced by LBADH even employing 2.5 equiv. of 2-propanol independently of their kinetic values. Finally, we found good correlations between the IR absorption band of the carbonyl groups and the degrees of conversion obtained in these HT processes, making this simple method a convenient tool to predict the success of these transformations. The Royal Society of Chemistry.
- Rodriguez, Cristina,Borzecka, Wioleta,Sattler, Johann H.,Kroutil, Wolfgang,Lavandera, Ivan,Gotor, Vicente
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supporting information
p. 673 - 681
(2014/01/06)
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- Diastereoselective lithiation of n-silyl-protected (S)-tetrahydro-1H- pyrrolo[1,2-c]imidazol-3(2H)-one
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An L-proline-derived imidazolone protected with an N-triethylsilyl (N-TES) group undergoes diastereoselective lithiation-electrophile quench to give C5-substituted products with syn stereochemistry. Unlike the previous N-t-Bu analogues, the N-TES derivatives may be easily N-desilylated to give secondary ureas that serve as precursors to N-phenyl chiral bicyclic guanidines.
- Metallinos, Costa,Sadraei, Seyed Iraj,Zhukovskaya, Nadezda
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p. 347 - 362
(2014/01/17)
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- β-Hydroxyamide-based ligands and their use in the enantioselective borane reduction of prochiral ketones
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Hydroxyamide-based ligands have occupied a considerable place in asymmetric synthesis. Here we report the synthesis of seven β-hydroxyamide-based ligands from the reaction of 2-hydroxynicotinic acid with chiral amino alcohols and test their effect on the enantioselective reduction of aromatic prochiral ketones with borane in tetrahydofuran (THF). They produce the corresponding secondary alcohols with up to 76% enantiomeric excess (ee) and good to excellent yields (86-99%). Chirality 26:21-26, 2013. 2013 Wiley Periodicals, Inc.
- Azizoglu, Murat,Erdogan, Asli,Arslan, Nevin,Turgut, Yilmaz
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- Synthesis of Di-, Tri-, and tetrasubstituted oxetanes by rhodium-catalyzed O-H insertion and C-C bond-forming cyclization
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Oxetanes offer exciting potential as structural motifs and intermediates in drug discovery and materials science. Here an efficient strategy for the synthesis of oxetane rings incorporating pendant functional groups is described. A wide variety of oxetane 2,2-dicarboxylates were accessed in high yields, including functionalized 3-/4-aryl-and alkyl-substituted oxetanes and fused oxetane bicycles. Enantioenriched alcohols provided enantioenriched oxetanes with complete retention of configuration. The oxetane products were further derivatized, while the ring was maintained intact, thus highlighting their potential as building blocks for medicinal chemistry.
- Davis, Owen A.,Bull, James A.
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supporting information
p. 14230 - 14234
(2015/02/19)
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- Catalytic asymmetric intermolecular bromoesterification of unfunctionalized olefins
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An asymmetric intermolecular bromoesterification of unfunctionalized olefins catalyzed by (DHQD)2PHAL is described. Optically active bromoesters can be obtained with up to 92% ee.
- Li, Lijun,Su, Cunxiang,Liu, Xiaoqin,Tian, Hua,Shi, Yian
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p. 3728 - 3731
(2014/08/05)
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- Mesoporous silica KIT-6 supported superparamagnetic CuFe2O 4 nanoparticles for catalytic asymmetric hydrosilylation of ketones in air
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A diverse range of prochiral ketones were reduced in air with high yields and good-to-excellent enantioselectivities (up to 97% ee) in the presence of a heterogeneous catalyst system, which was in situ formed from catalytic amounts of superparamagnetic CuFe2O4 nanoparticles supported on mesoporous silica KIT-6 and non-racemic dipyridylphosphine ligand, the stoichiometric hydride donor polymethylhydrosiloxane (PMHS) as well as certain amounts of additives. The magnetically separable catalysts could be efficiently reused 4 times without apparent loss of both the activity and enantioselectivity. the Partner Organisations 2014.
- Li, Min,Li, Bin,Xia, Hong-Feng,Ye, Danru,Wu, Jing,Shi, Yifeng
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p. 2680 - 2688
(2014/05/06)
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- Facile access to chiral alcohols with pharmaceutical relevance using a ketoreductase newly mined from Pichia guilliermondii
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Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones offers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y-324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2-bromoacetophenone (93.5% ee). Semi-preparative reduction of six ketones was achieved with high enantioselectivity (>99% ee) and isolation yields (>80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers. Copyright
- Xu, Guochao,Yu, Huilei,Xu, Jianhe
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p. 349 - 354
(2013/08/22)
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- β-Hydroxyamide derivatives of salicylic acid as organocatalysts for enantioselective reductions of prochiral ketones
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In order to find the most effective catalyst for the enantioselective reduction of a prochiral ketone, a series of novel β-hydroxyamide derivatives of salicylic acid and chiral amino alcohols were synthesized. Different substituted prochiral ketones have been reduced in high yield (up to 99%) and the corresponding secondary alcohols are formed with good enantiomeric excess (up to 86%). The mechanism of this type of catalyst can be explained by considering the reaction mechanism for the CBS catalyst.
- Turgut, Yilmaz,Azizoglu, Murat,Erdogan, Asli,Arslan, Nevin,Hosgoren, Halil
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p. 853 - 859
(2013/08/23)
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- Surfactant-accelerated asymmetric transfer hydrogenation with recyclable water-soluble catalyst in aqueous media
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Water-soluble ligands (R,R)-2 were successfully prepared, in which the bis-meta-sulphonated ligand was definitely detected as the major product. The corresponding transition-metal complexes containing the ligands displayed excellent catalytic performance in asymmetric transfer hydrogenation (ATH) of aromatic ketones. Especially, the aromatic ketones with a bromine group in the α position could be smoothly reduced to the expected alcohol, keeping the bromine group intact with excellent enantioselectivities (up to 96% ee). The catalyst could be reused at least 21 times without erosion of the enantioselectivity in high conversion. Moreover, it was found that cationic surfactant and proper pH values were necessary for the maintenance of high reactivity.
- Li, Jiahong,Li, Xuefeng,Ma, Yaping,Wu, Jiashou,Wang, Fei,Xiang, Jing,Zhu, Jin,Wang, Qiwei,Deng, Jingen
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p. 1825 - 1834
(2013/03/14)
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- Synthesis of optically active α-bromohydrins via reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase
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Enantiomerically pure (S)-α-bromohydrins were prepared by the reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase from Candida magnolia with high yield and excellent enantiomeric excess when methyl tert-butyl ether was employed as the co-solvent, while avoiding the formation of by-products. This provides a new approach to access these chiral α-bromohydrins which are of pharmaceutical importance.
- Ren, Jie,Dong, Wenyue,Yu, Benqing,Wu, Qiaqing,Zhu, Dunming
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experimental part
p. 497 - 500
(2012/07/28)
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- On the preparation and determination of configurational stability of chiral thio- and bromo[D1]methyllithiums
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Thio- and bromo[D1]methyllithiums (ee 99%) were generated from the respective stannanes by tin-lithium exchange at temperatures ranging from 0 to -95 °C. Thio[D1]methyllithiums 6 were found to be microscopically configurationally labile on the time scale of the thiophosphate-α-mercaptophosphonate rearrangement even at -95 °C. Thio[D1]methyllithiums 13a and 13b underwent a thia-[2,3]-Wittig rearrangement down to -95 °C and 13b only down to -50 °C. The former were microscopically configurationally stable below -95 °C, and the latter racemized completely at -50 °C. Chiral bromo[D1]methyllithiums are chemically unstable at -78 °C but microscopically configurationally stable at the time scale of their addition to benzaldehyde and acetophenone.
- Wieczorek, Anna,Hammerschmidt, Friedrich
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p. 10021 - 10034
(2013/01/15)
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- Efficient synthesis of a chiral precursor for angiotensin-converting enzyme (ace) inhibitors in high space-time yield by a new reductase without external cofactors
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A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L-1·d -1) was 27 times higher than the highest record.
- Shen, Nai-Dong,Ni, Yan,Ma, Hong-Min,Wang, Li-Juan,Li, Chun-Xiu,Zheng, Gao-Wei,Zhang, Jie,Xu, Jian-He
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supporting information; experimental part
p. 1982 - 1985
(2012/06/01)
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- Efficient synthesis of (R)-2-chloro-1-(3-chlorophenyl)ethanol by permeabilized whole cells of candida ontarioensis
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(R)-2-Chloro-1-(3-chlorophenyl)ethanol is a key pharmaceutical intermediate in the synthesis of β3-adrenoceptor receptor (β;3-AR) agonists. The asymmetric reduction of 2-chloro-1-(3-chlorophenyl)ethanone to (R)-2-chloro-1-(3-chlorophenyl)ethanol catalyzed by resting cells of Candida ontarioensis was studied. At a substrate concentration of 10 g/L, the microbial cells showed excellent catalytic activity under the optimum reaction conditions, giving the product in 99.9% ee and 99.0% yield. After cetyltrimethylammonium bromide-pretreatment, the activity of permeabilized Candida ontarioensis cells was increased by more than 2-fold and the product could be produced over the significantly shortened reaction period of 24 h in 99.9% ee and 97.5%yield at a substrate concentration of 30 g/L. This work provides a practical approach for the efficient preparation of the important chiral intermediate (R)-2-chloro-1-(3-chlorophenyl) ethanol.
- Ni, Ye,Zhang, Beihua,Sun, Zhihao
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scheme or table
p. 681 - 687
(2012/08/08)
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- Asymmetric synthesis of β-adrenergic blockers through multistep one-pot transformations involving in situ chiral organocatalyst formation
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Two birds one stone: A new atom-economical one-pot approach to enantioselective chiral drug synthesis, involving in situ multistep organocatalyst formation and the application of the reaction for multistep sequential synthesis of β-adrenergic blockers is disclosed (see scheme).
- Wei, Shengwei,Messerer, Regina,Tsogoeva, Svetlana B.
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supporting information; scheme or table
p. 14380 - 14384
(2012/02/01)
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- A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane
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A novel C3-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity. Copyright
- Wu, Xiang-Fei,Min, Chang,Nyamzundui, Enkhtsetseg,Zhou, Hai-Bing,Dong, Chune
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experimental part
p. 1640 - 1643
(2011/12/22)
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- Chiral epoxides via borane reduction of 2-haloketones catalyzed by spiroborate ester: Application to the synthesis of optically pure 1,2-hydroxy ethers and 1,2-azido alcohols
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An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield. 2011 American Chemical Society.
- Huang, Kun,Wang, Haiyang,Stepanenko, Viatcheslav,De Jesus, Melvin,Torruellas, Carilyn,Correa, Wildeliz,Ortiz-Marciales, Margarita
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supporting information; experimental part
p. 1883 - 1886
(2011/06/20)
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- Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: Highly enantioselective synthesis of valuable alcohols
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In the presence of PhSiH3 as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)2·H 2O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9 % enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10 000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98 % ee) and exceedingly high turn-over rates (up to 50 000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.
- Yu, Feng,Zhou, Ji-Ning,Zhang, Xi-Chang,Sui, Yao-Zong,Wu, Fei-Fei,Xie, Lin-Jie,S. C. Chan, Albert,Wu, Jing
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supporting information; scheme or table
p. 14234 - 14240
(2012/01/12)
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- NOVEL TRICYCLIC CHIRAL COMPOUNDS AND THEIR USE IN ASYMMETRIC CATALYSIS
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The present invention relates to a compound of general Formula (XX), its formation and its use in asymmetric catalysis. In Formula (XX) R and R31 are independently —COOR3, —R4COOR3, —R4CHO, —R4COR3, —R4CONR5R6, —R4COX, —R4OP(═O)(OH)2, —R4P(═O)(OH)2), —R4C(O)C(R3)CR5R6 and —R4CO2COR3. In addition, R31 may also be hydrogen. R3, R5 and R6 are independently hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group or an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si. R4 an aliphatic bridge with a main chain having 1 to about 20 carbon atoms, an alicyclic bridge, an aromatic bridge, an arylaliphatic bridge or an arylalicyclic bridge, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and X is halogen. In Formula (XX) R30 is —C(OH)R1R2 or —COOR14, wherein R1, R2 and R14 are independently hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group or an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si.
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Page/Page column 26; Sheet 11
(2011/11/12)
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- Efficient reduction of ethyl 2-oxo-4-phenylbutyrate at 620 ?l -1 by a bacterial reductase with broad substrate spectrum
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A β-ketoacyl-ACP reductase (FabG) gene from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli and the encoded protein was purified to homogeneity. The recombinant reductase could reduce a broad spectrum of prochiral ketones including aromatic ketones and keto esters and showed the highest activity in the asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). Using E. coli cells coexpressing both FabG and glucose dehydrogenase (GDH) genes, as much as 620 ?L-1 of OPBE was almost stoichiometrically converted to ethyl (S)-2-hydroxy-4-phenylbutyrate [(S)-HPBE] with excellent (>99%) enantiomeric excess. More importantly, the process could be performed smoothly without external addition of an expensive cofactor as usually done and could be scaled up very easily. All these positive features demonstrate the applicability of this reductase for the large-scale production of optically active α-hydroxy acids/esters.
- Ni, Yan,Li, Chun-Xiu,Zhang, Jie,Shen, Nai-Dong,Bornscheuer, Uwe T.,Xu, Jian-He
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supporting information; experimental part
p. 1213 - 1217
(2011/07/09)
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