- Enantioselective catalytic synthesis of ethyl mandelate derivatives using Rh(I)-NHC catalysts and organoboron reagents
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Herein we describe for the first time the enantioselective catalytic arylation of ethyl glyoxalate using phenylboron reagents and chiral rhodium(I)-NHC catalysts. KOtBu was the base of choice, along with tert-amyl alcohol as the solvent. A novel chiral bis-imidazolium salt was synthesized and evaluated for the first time in this catalytic transformation. Although moderate enantioselectivities (up to 34% ee) were obtained for the phenylation reaction, despite the excellent yields, very low enantioselectivities were obtained using other arylboronic acids with a variety of chiral rhodium(I)-NHC catalysts.
- Marques, Carolina S.,Burke, Anthony J.
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- Chiral organometallic NADH mimics: Highly stereoselective reductions of ethyl benzoylformate with a 1,4-dihydronicotinoyl fragment attached to the homochiral auxiliary 5-C5H5)Fe(CO)(PPh3)> and possessing a homochiral β-hydroxy-carboxamide at C-5.
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A series of homochiral organometallic NADH mimics incorporating the chiral auxiliary 5-C5H5)Fe(CO)(PPh3)> at the C-3 carbonyl and a chiral carboxamide at C-5 of a 1,4-dihydronicotinoyl fragment have been prepared.These complexes were shown to stereoselectively reduce ethyl benzoylformate to either (R)- or (S)-ethyl mandelate by a combination of steric and chelation control.For example, complex (R,R)-12 bearing a carboxamide derived from (R)-(+)-methylbenzylamine afforded (R)-ethyl mandelate in 89percent enantiomeric excess.Utilisation of complexes (R,S)-19a and (R,R,S)-22a bearing chiral β-hydroxy-carboxamides derived from valinol and norephedrine respectively gave the (R)-ethyl mandelate in greater than 97percent enantiomeric excess.
- Burgess, Vicky A.,Davies, Stephen G.,Skerlj, Renato T.,Whittaker, Mark
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- Chiral-at-Iron Catalyst: Expanding the Chemical Space for Asymmetric Earth-Abundant Metal Catalysis
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A new class of chiral iron catalysts is introduced that contains exclusively achiral ligands with the overall chirality being the result of a stereogenic iron center. Specifically, iron(II) is cis-coordinated to two N-(2-pyridyl)-substituted N-heterocycli
- Hong, Yubiao,Jarrige, Lucie,Harms, Klaus,Meggers, Eric
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- Stereoselective reductions with macrocyclic NADH models
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Macrocyclic NADH models with two (C2 symmetry) or four (D2 symmetry) nicotinamide units comprised in a ring have been prepared and found to reduce activated carbonyl compounds in good yields and high enantiomeric excess. The roles of magnesium ions as a cocatalyst and the temperature have also been investigated. The smaller, C2-symmetric macrocycle gave 96% ee upon reduction of ethyl benzoylformate whereas the best result with the larger D2-symmetric model was 81% ee for the reduction of methyl benzoylformate. (C) 2000 Elsevier Science Ltd.
- Gran, Ulrik,Wennerstroem, Olof,Westman, Gunnar
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- Copper encapsulated alkaloids composite: An effective heterogeneous catalyst for electrocatalytic asymmetric hydrogenation
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A novel heterogeneous catalyst, alkaloid@Cu was prepared by the entrapment of commercially purchased alkaloids within non-noble metallic copper nanoparticles. This composite was compacted into a coin and directly used as cathode for electrocatalytic asymmetric hydrogenation of aromatic ketones. Using water as hydrogen source, optically active alcohols with 71% ee value and 93% yield were obtained under very mild conditions.
- Yang, Heng-Pan,Fen, Qiu,Wang, Huan,Lu, Jia-Xing
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- Steric and electronic effects in the enantioselective hydrogenation of activated ketones on platinum: Directing effect of ester group
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Steric effects in the Pt-catalyzed asymmetric hydrogenation of nine different α-ketoesters were studied by variation of the bulkiness at the keto and ester side of the substrates, and by using cinchonidine (CD), its 6′-methoxy derivative quinine, and o-ph
- Diezi, Simon,Reimann, Sven,Bonalumi,Mallat, Tamas,Baiker, Alfons
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- Stereocontrolled reduction of α- and β-keto esters with micro green algae, Chlorella strains
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The stereocontrolled reduction of α- and β-keto esters using micro green algae was accomplished by a combination of the cultivation method and the introduction of an additive. The reduction of ethyl pyruvate and ethyl benzoylformate by the photoautotrophically cultivated Chlorella sorokiniana gave the corresponding alcohol in high e.e. (>99% e.e. (S) and >99% e.e. (R), respectively). In the presence of glucose as an additive, the reduction of ethyl 3-methyl-2-oxobutanoate by the heterotrophically cultivated C. sorokiniana afforded the corresponding (R)-alcohol. On the other hand, the reduction in the presence of ethyl propionate gave the (S)-alcohol. Ethyl 2-methyl-3-oxobutanoate was reduced in the presence of glycerol by the photoautotrophically cultivated C. sorokiniana or the heterotrophically cultivated C. sorokiniana to the corresponding syn-(2R,3S)-hydroxy ester with high diastereo- and enantiomeric excess (e.e.). Some additives altered the stereochemical course in the reduction of α- and β-keto esters.
- Ishihara, Kohji,Yamaguchi, Hitomi,Adachi, Noriko,Hamada, Hiroki,Nakajima, Nobuyoshi
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- Enzymatic enantioselective reduction of α-ketoesters by a thermostable 7α-hydroxysteroid dehydrogenase from Bacteroides fragilis
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A thermostable 7α-hydroxysteroid dehydrogenase (7-HSDH) from Bacteroides fragilis ATCC 25285 was cloned and over-expressed in E. coli, and its substrate specificity and stereoselectivity toward reduction of various ketones were examined. This alcohol dehydrogenase was active toward a series of aromatic and bulky aliphatic α-ketoesters. The substituents at the phenyl ring of aromatic α-ketoesters greatly affected the activity, but their effects on enantioselectivity were minimal. The synthetic application of this enzyme was then demonstrated through the preparation of a few α-hydroxy carboxylic acid esters of pharmaceutical interest.
- Zhu, Dunming,Stearns, Jennifer Elisabeth,Ramirez, Monica,Hua, Ling
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- Enantioselective synthesis of ethyl (S)-2-hydroxy-4-phenylbutyrate by recombinant diketoreductase
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Recombinant diketoreductase showed excellent stereoselectivity in the double reduction of β,δ-diketo esters. To investigate the substrate specificity and to broaden the applications of this new biocatalyst, a number of ketone substrates were used to evaluate the substrate spectrum and enantioselectivity of this enzyme in the present study. Among the ketone substrates tested, only this enzyme displayed high efficiency and excellent enantioselectivity in the reduction of ethyl 2-oxo-4-phenylbutyrate to ethyl (S)-2-hydroxy-4-phenylbutyrate. After optimizing the reaction conditions, the bio-reduction of ethyl 2-oxo-4-phenylbutyrate at a substrate concentration of 0.8 M (164.8 g/L) was achieved by the recombinant diketoreductase in an aqueous-toluene biphasic system coupled with formate dehydrogenase for the regeneration of cofactor, resulting in an overall hydroxyl product yield of 88.7% (99.5% ee). This new enzymatic transformation may offer a practical method for the preparation of this important chiral building block.
- Wu, Xuri,Wang, Yuchen,Ju, Jianming,Chen, Chen,Liu, Nan,Chen, Yijun
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- A homochiral porous metal-organic framework for enantioselective adsorption of mandelates and photocyclizaton of tropolone ethers
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A chiral porous metal-organic framework of an axially C2- symmetric 1,1′-biphenol ligand is constructed and can be used as a solid-state host to enanioselectively adsorb mandelates with up to 93.1% ee and to entrap achiral tropolone ethers and
- Peng, Yongwu,Gong, Tengfei,Cui, Yong
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- Alkaloid-induced asymmetric hydrogenation on a Cu nanoparticle cathode by electrochemical conditions
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Copper nanoparticles were prepared in an aqueous solution, compacted into a coin, and used as a cathode for asymmetric hydrogenation by the electrochemical method for the first time. A good ee value and excellent yield were obtained under mild conditions. Electrochemical conditions were crucial for alkaloid adsorption on metallic Cu, which is a key process of asymmetric induction. Furthermore, the ee value was linear with an adsorption amount.
- Yang, Heng-Pan,Wang, Huan,Lu, Jia-Xing
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- Biocatalysed reductions of α-ketoesters employing CyreneTM as cosolvent
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The search for novel reaction media with environmental friendly properties is an area of great interest in enzyme catalysis. Water is the medium of biocatalysed processes, but due to its properties, sometimes the presence of organic (co)solvents is required. CyreneTM represents one of the newest approaches to this medium engineering. This polar solvent has been employed for the first time in biocatalysed reductions employing purified alcohol dehydrogenases. A set of α-ketoesters has been reduced to the corresponding chiral α-hydroxyesters with high conversions and optical purities, being possible to obtain good results at Cyrene contents of 30% v/v and working at substrate concentrations of 1.0 M in presence of 2.5% v/v of this solvent. At this concentration, the presence of Cyrene has a beneficial effect in the bioreduction conversion.
- de Gonzalo, Gonzalo
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- On-Column Reaction Set-Up for High-Throughput Screenings and Mechanistic Investigations
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A screening platform, which offers a high-throughput approach as well as an easy investigation of kinetic isotope effects, applicable to a wide range of reactions is presented. To illustrate the high potential of this approach, the asymmetric transfer hydrogenation of methyl benzoylformate with copper(II) bis(oxazoline) and Hantzsch ester was examined. Accordingly, the enantioselectivities of the reaction performed on-column in a microcapillary were comparable to standard reaction conditions, however, we were able achieve catalysis and analysis in a single step in less than 30 min. The throughput can be increased by simultaneous investigation of different substrates without increasing the overall analysis time. Use of di-deuterated Hantzsch ester allowed us to investigate the kinetic isotope effect of the transfer hydrogenation reaction only requiring a minute amount of the deuterated transfer hydrogenation reagent. Hence we were able to get further insights into the mechanism of the asymmetric transfer hydrogenation using Hantzsch ester as hydrogen source. The here presented technique is broadly applicable to study isotope effects on a very small scale, which is a rapid and an inexpensive alternative compared to conventional experiments.
- Stockinger, Skrollan,Troendlin, Johannes,Rominger, Frank,Trapp, Oliver
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- Enantioselective hydrogenation of α-ketoesters over alkaloid-modified platinum nanowires
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A green process for enantioselective hydrogenation of α-ketoesters over cinchona alkaloid-modified platinum (Pt) nanowires has been developed. Pt nanowires with a diameter of ～1 nm were successfully synthesized, and used for the asymmetric hydrogenation of α-ketoesters in the presence of cinchona alkaloids under a low pressure at room temperature in water. Quantitative yields and excellent enantioselectivity of up to 78% were achieved. The catalyst along with the modifier was recycled multiple times without any significant loss in activity or selectivity. To our knowledge, such a catalyst system is unprecedented for asymmetric hydrogenation of α-ketoesters. The Royal Society of Chemistry.
- Erathodiyil, Nandanan,Gu, Hongwei,Shao, Huilin,Jiang, Jiang,Ying, Jackie Y.
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- Asymmetric Reduction of α-Keto Esters with Potassium 9-O-(1,2:5,6-Di-O-isopropylidene-α-D-glucofuranosyl)-9-boratabicyclononane. Chiral Synthesis of α-Hydroxy Esters with Optical Purity Approaching 100percent ee
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The asymmetric reduction of α-keto esters with potassium 9-O-(1,2:5,6-di-O-isopropylidene-α-D-glucofuranosyl)-9-boratabicyclononane (K 9-O-DIPGF-9-BBNH) to the corresponding α-hydroxy esters in optical purities approaching 100percent ee has been ac
- Brown, Herbert C.,Cho, Byung Tae,Park, Won Suh
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- Efficient heterogeneous asymmetric transfer hydrogenation catalyzed by recyclable silica-supported ruthenium complexes
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Easily accessible N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine-(TsDPEN-) derived organic-inorganic hybrid ligands were prepared and applied to the heterogeneous asymmetric transfer hydrogenation in traditional HCO 2H/NEt3 and in w
- Liu, Pei-Nian,Gu, Pei-Ming,Deng, Jin-Gen,Tu, Yong-Qiang,Ma, Ya-Ping
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- Preparation of γ-Al2O3/α-Al2O3 ceramic foams as catalyst carriers via the replica technique
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This work describes an effective method for the preparation of open-cell ceramic foams for their further use as catalyst supports. The polyurethane sponge replica technique was applied using a ceramic suspension based on a mixture of α-alumina, magnesia a
- Shumilov, Vladimir,Kirilin, Alexey,Tokarev, Anton,Boden, Stephan,Schubert, Markus,Hampel, Uwe,Hupa, Leena,Salmi, Tapio,Murzin, Dmitry Yu.
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- Compensation effect between differential activation enthalpy and entropy in subtilisin-catalyzed kinetic resolutions of secondary alcohols
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Thermodynamic parameters for subtilisin-catalyzed kinetic resolutions of secondary alcohols were determined, and a compensation effect between ΔΔH? and ΔΔS? was found. These data are explained in terms of the transition-state model.
- Ema, Tadashi,Yamaguchi, Kunihiro,Wakasa, Yuji,Tanaka, Nobuaki,Utaka, Masanori,Sakai, Takashi
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- Stereoselective reduction of carbonyl compounds using the cell-free extract of the earthworm, Lumbricus rubellus, as a novel source of biocatalyst
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We found the reducing activity toward carbonyl compounds in the cell-free extract of the earthworm, Lumbricus rubellus. The earthworm extract had a reducing activity for keto esters in the presence of NADH or NADPH as a coenzyme. The earthworm extract red
- Ishihara, Kohji,Nakajima, Nobuyoshi
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- Kinetics and catalyst deactivation in the enantioselective hydrogenation of ethyl benzoylformate over Pt/Al2O3
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The enantioselective hydrogenation of ethyl benzoylformate (EBF) to (R)-ethyl mandelate(-)-cinchonidine (CD)-modified Pt/Al2O 3 catalyst in toluene in a semi-batch reactor was studied as a function of modifier concentration, reaction temperature, stirring rate and catalyst particle size. The kinetic results showed higher enantioselectivity and lower initial rates tending asymptotically to a constant value as the amount of modifier increased. The maximum enantiomeric excess (ee) and the initial hydrogenation rate or turnover frequency obtained under optimized conditions with an initial concentration of 5.6 mmol L-1 EBF at 25°C5% (w/w) Pt/Al2O3 were 85% (modifier-to-surface Pt of 1.28) and 109 h-1 (modifier-to-surface Pt of 0.16), respectively. Additionally, catalyst deactivation due to the presence of impurities in the feed was prominent in some cases; therefore activated carbon was used as a cleaning agent of the raw material to remove impurities prior to catalyst addition.
- Martin, Gerson,Maeki-Arvela, Paeivi,Murzin, Dmitry Yu.,Salmi, Tapio
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- Asymmetric Reduction with L-Proline Amide Derivatives of 1,4-Dihydronicotinamide
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The magnesium perchlorate-, zinc chloride-, and cobalt chloride-catalysed asymmetric reduction of ethyl benzoylformate with 1,4-dihydronicotinamides carrying an L-proline amide in the 3-carbamoyl side-chain afforded R-mandelate, the asymmetric yields bein
- Baba, Naomichi,Oda, Jun'ichi,Inouye, Yuzo
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- Enantioselective α-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3
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Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the α-hydroxylation of phenylacetic acid esters. This P450 BM-3 variant also produces the authentic human metabolite of buspirone, R-6-hydroxybuspir
- Landwehr, Marco,Hochrein, Lisa,Otey, Christopher R.,Kasrayan, Alex,Baeckvall, Jan-E.,Arnold, Frances H.
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- Enantioselective hydrogenation of α-ketoesters catalyzed by cinchona alkaloid stabilized Rh nanoparticles in ionic liquid
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The heterogeneous enantioselective hydrogenation of α-ketoesters catalyzed by rhodium nanoparticles (Rh NPs) in ionic liquid was studied with the stabilization and modification of cinchona alkaloids. TEM characterization showed that well-dispersed Rh NPs of about 1.96?nm were obtained in ionic liquid. The results showed that cinchona alkaloids not only had good enantiodifferentiating ability but also accelerated the catalytic reaction. Under the optimum reaction conditions, the enantiomeric excess in ethyl benzoylformate hydrogenation could reach as high as 60.9%.
- Jiang, He-yan,Xu, Jie,Sun, Bin
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- Bioreduction with Immobilized Bakers' Yeast in Hexane using Alcohols as an Energy Source
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Bioreduction with immobilized bakers' yeast proceeded smoothly in hexane by using alcohols, such as methanol, ethanol, and propan-2-ol, instead of glucose, as an energy source; ethyl 3-oxobutanoate and ethyl benzoylformate were each reduced to the corresp
- Naoshima, Yoshinobu,Maeda, Jusei,Munakata, Yoshihito,Nishiyama, Tadashi,Kamezawa, Makoto,Tachibana, Hojun
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- Chiral Organometallic NADH Mimics: Stereoselective Reduction of Ethyl Benzoylformate Utilising the Homochiral Auxiliary 5-C5H5)Fe(CO)(PPh3)> at C-3 and a Chiral β-Hydroxy-carboxamide Derived from Valinol at C-5
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Homochiral complexes incorporating the chiral auxiliary 5-C5H5)Fe(CO)(PPh3)> at C-3 and a chiral β-hydroxy-carboxamide, derived from valinol, at C-5 reduce ethyl benzoylformate to ethyl mandelate in greater than 97percent enantiomeric excess.
- Burgess, Vicky A.,Davies, Stephen G.,Skerlj, Renato T.
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- Solvent effects in the enantioselective hydrogenation of ethyl benzoylformate
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Solvent effects in the enantioselective hydrogenation of ethyl benzoylformate (EBF) to (R)-ethyl mandelate(-)-cinchonidine (CD)-modified Pt/Al2O3 catalyst were studied in a semi-batch reactor. Solvents of different nature were used:
- Martin, Gerson,Maeki-Arvela, Paeivi,Murzin, Dmitry Yu.,Salmi, Tapio
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- Immobilized baker's yeast reduction in fluorous media
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The first example of immobilized bakers' yeast mediated reduction of ketones in fluorous media is described. The use of fluorous media permits simple work-up and reuse of the solvent without any purification.
- Yajima, Arata,Naka, Kazumi,Yabuta, Goro
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- Mandelohydroxamic acid as ligand for copper(II) 15-metallacrown-5 lanthanide(III) and copper(II) 15-metallacrown-5 uranyl complexes
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The formation of pentanuclear copper(II) complexes with the mandelohydroxamic ligand was studied in solution by electrospray ionization mass spectrometry (ESI-MS), absorption spectrophotometry, circular dichroism and 1H NMR spectroscopy. The pr
- Parac-Vogt, Tatjana N.,Pacco, Antoine,Nockemann, Peter,Yuan, Yao-Feng,Goerller-Walrand, Christiane,Binnemans, Koen
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- A carbonyl reductase from: Candida parapsilosis ATCC 7330: Substrate selectivity and enantiospecificity
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Candida parapsilosis ATCC 7330, a rich source of highly stereospecific oxidoreductases, catalyzes oxidation-reduction of a plethora of compounds yielding industrially important intermediates. An (S)-specific carbonyl reductase (SRED) purified and characterized from this yeast is reported here. (R)-Specific carbonyl reductase (CpCR) was reported by us earlier. SRED asymmetrically reduces ketones with excellent enantiospecificity (ee > 99%) and α-ketoesters with higher catalytic activity but moderate enantiospecificity (ee 70%) in the presence of NADPH. Minimal activity is shown towards the reduction of aldehydes. While the reduction of α-ketoesters with SRED can occur with either NADPH or NADH, for ketone reduction SRED requires NADPH specifically. SRED with a subunit molecular weight of 30 kDa shows optimal activity at pH 5.0 and 25 °C, and its activity is affected by Cu2+. Taken together, SRED and CpCR offer substrates which on asymmetric reduction give products of opposite absolute configurations.
- Sudhakara, Sneha,Chadha, Anju
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- Structure-guided evolution of carbonyl reductase for efficient biosynthesis of ethyl (: R)-2-hydroxy-4-phenylbutyrate
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Ethyl (R)-2-hydroxy-4-phenylbutanoate ((R)-HPBE) is an important versatile intermediate for the synthesis of angiotensin-converting enzyme inhibitors. Herein, a structure-guided rational design was adopted to improve the catalytic performance of carbonyl reductase from Gluconobacter oxydans (GoCR) for efficient production of (R)-HPBE at high substrate loading. To enhance the catalytic performance of GoCR, three sites (Cys93, Ile187 and Trp193) were identified based on a computational approach. Through single-site and cooperative mutation at these three sites, four variants with simultaneous increase in stereoselectivity and catalytic efficiency were obtained. Variants mut-W193L, mut-W193L/C93I, mut-W193L/I187L and mut-W193L/C93I/I187L exhibited 9.8-to 37.0-fold increase in catalytic efficiency (kcat/Km) compared to the wild-type enzyme. Meanwhile, the stereoselectivities of these variants were improved from 43.0% ee of wild-type GoCR to >99% ee. In addition, mut-W193L/C93I/I187L displayed improved thermostability simultaneously. Theoretical structural analysis revealed that the changes in the catalytic pocket microenvironment resulted in the concurrent improvement of enzyme activity and thermostability. In the batch production of (R)-HPBE, up to 371 g L-1 substrate loading was completely reduced by utilizing the most efficient variant mut-W193L/C93I/I187L at 40 °C, affording (R)-HPBE with >99% ee and a space-time yield of 540.4 g L-1 per day. This study provides a potential and attractive biocatalyst for the efficient synthesis of (R)-HPBE.
- Chen, Chao,Chen, Lulu,Deng, Jian,Kuang, Yuyao,Lin, Jinping,Tang, Wen,Wang, Hualei,Wei, Dongzhi,Yin, Bo
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- (R)-binap-mediated asymmetric hydrogenation with a rhodacarborane catalyst in ionic-liquid media
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Unsymmetrical aryl ketones undergo asymmetric hydrogenation in ionic-liquid media in the presence of (R)-binap and a rhodacarborane catalyst derived from the suicide precursor 1 (see scheme). Ketones that are poor substrates for other methods can be hydro
- Yinghuai, Zhu,Carpenter, Keith,Bun, Ching Chi,Bahnmueller, Stefan,Ke, Chan Pek,Srid, Venugopal Shanmugham,Kee, Leong Weng,Hawthorne, M. Frederick
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- Cu(II)-aza(bisoxazoline)-catalyzed asymmetric benzoylations
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(Chemical Equation Presented) Racemic 1,2-diols and α-hydroxy carbonyl compounds can be asymmetrically benzoylated in a kinetic resolution in the presence of various Cu(II)-aza(bisoxazoline) catalysts. A novel bisbenzyl-substituted aza(bisoxazoline) ligand proved to be especially effective when immobilized on MeOPEG5000, giving from 91 to ≥99% ee in 37-49% yield for each of five sequential reactions.
- Gissibi, Anja,Finn,Reiser, Oliver
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- ASYMMETRIC OXIDATION OF OLEFINS WITH OSMIUM TETROXIDE COORDINATED BY CHIRAL DIAMINES DERIVED FROM L-TARTARIC ACID
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The enantioselective oxidation of olefins with OsO4 coordinated by chiral diamines derived from L-tartaric acid is described.Phenylketene dimethylacetal and trans-stilbene are converted to (R)-methyl mandelate and (1R,2R)-1,2-diphenyl-1,2-ethanediol with
- Yamada, Tohru,Narasaka, Koichi
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- Optically active furanoids containing cytosine-, adenine-and nicotinamide-like moieties
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3-Hydroxymethyl-5-(2,3-O-isopropylidene-β-D-erythro-furanosyl)-2- methylfuran (2) prepared from 3-ethoxycarbonyl derivative 1 was converted to 3-chloromethyl-5-(2,3-O-isopropylidene-β-D-erythrofuranosyl)-2-methylfuran (3). Compound 3 reacted with cytosine
- Werfeli, Ali,Voltrova, Svatava,Prutianov, Viktor,Kuthan, Josef
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- Chiral ferrocene-indole diphosphine ligand as well as preparation method and application thereof
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The invention relates to a chiral ferrocene-indole diphosphine ligand as well as a preparation method and application thereof. The specific preparation method comprises the following steps: dissolving an indole compound and a chiral ferrocene phosphine ac
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Paragraph 0079-0080
(2021/05/22)
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- Preparation method (1R,3S)-3- amino cyclopentanol chiral acid salt (by machine translation)
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The invention discloses a preparation method (1R,3S) - 3 - of, amino cyclopentanol chiral acid salt, wherein the (1R,3S) - 3 - amino cyclopentanol chiral acid salt is a compound, of formula I and comprises a step e or step d-e or step c-d-e or step a-b-c-
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Paragraph 0036-0039
(2020/05/01)
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- Ferroceno quinoline compound with planar chirality and synthesis method thereof
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The invention provides a ferroceno quinoline compound with planar chirality as shown in description, R1-R8 are H or C1-C10 alkyl, the C1-C10 alkyl comprises one or multiple substituents of the methoxyand halogen. The invention further provides a synthesis
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Paragraph 0058-0060
(2019/06/07)
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- Exploiting Cofactor Versatility to Convert a FAD-Dependent Baeyer–Villiger Monooxygenase into a Ketoreductase
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Cyclohexanone monooxygenases (CHMOs) show very high catalytic specificity for natural Baeyer–Villiger (BV) reactions and promiscuous reduction reactions have not been reported to date. Wild-type CHMO from Acinetobacter sp. NCIMB 9871 was found to possess an innate, promiscuous ability to reduce an aromatic α-keto ester, but with poor yield and stereoselectivity. Structure-guided, site-directed mutagenesis drastically improved the catalytic carbonyl-reduction activity (yield up to 99 %) and stereoselectivity (ee up to 99 %), thereby converting this CHMO into a ketoreductase, which can reduce a range of differently substituted aromatic α-keto esters. The improved, promiscuous reduction activity of the mutant enzyme in comparison to the wild-type enzyme results from a decrease in the distance between the carbonyl moiety of the substrate and the hydrogen atom on N5 of the reduced flavin adenine dinucleotide (FAD) cofactor, as confirmed using docking and molecular dynamics simulations.
- Xu, Jian,Peng, Yongzhen,Wang, Zhiguo,Hu, Yujing,Fan, Jiajie,Zheng, He,Lin, Xianfu,Wu, Qi
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supporting information
p. 14499 - 14503
(2019/09/17)
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- Asymmetric Transfer Hydrogenation in Thermomorphic Microemulsions Based on Ionic Liquids
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A thermomorphic ionic-liquid-based microemulsion system was successfully applied for the Ru-catalyzed asymmetric transfer hydrogenation of ketones. On the basis of the temperature-dependent multiphase behavior of the targeted microemulsion, simple product separation as well as catalyst recycling could be realized. The use of water-soluble ligands improved the immobilization of the catalyst in the microemulsion phase and significantly decreased the catalyst leaching into the organic layer upon extraction of the product. Eventually, the optimized microemulsion system could be applied to a wide range of aromatic ketones that were reduced with good isolated yields (up to 98%) and enantioselectivities (up to 97%), while aliphatic ketones were less successful.
- Hejazifar, Mahtab,Pálv?lgyi, ádám Márk,Bitai, Jacqueline,Lanaridi, Olga,Bica-Schr?der, Katharina
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p. 1841 - 1851
(2019/10/11)
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- A (1 R, 3 S) -3 - amino-cyclopentanol hydrochloride preparation method (by machine translation)
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The invention discloses a (1 R, 3 S) - 3 - amino-cyclopentanol hydrochloride of the preparation method, the method using chiral carboxylic acid with hydroxylamine to form the amide as chiral source, in copper catalyzed oxidation in the reaction system to rapidly obtain a chiral Diels - alder reaction product, after passes through the reduction reaction and alkaline deprotection reaction, and acidified after reaction to obtain the target product. Chiral inducing reagent chiral carboxylic acid by simple acidification, extraction processing can be reclaimed and reused. This kind of (1 R, 3 S) - 3 - amino-cyclopentanol hydrochloride preparation method has high operation safety and high selectivity, raw materials are easy, and the cost is low, the reaction time is short and simple process flow and the like. (by machine translation)
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Paragraph 0024
(2019/05/08)
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- Fine tuning the enantioselectivity and substrate specificity of alcohol dehydrogenase from Kluyveromyces polysporus by single residue at 237
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Here, S237 was identified to be important in fine tuning the substrate specificity and enantioselectivity of alcohol dehydrogenase from Kluyveromyces polysporus (KpADH). In the reduction of a diaryl ketone, (4-chlorophenyl)-(pyridin-2-yl)-methanone (1a), the highest and lowest enantioselectivity of 96.1% and 27.0% e.e. (R) were obtained with S237A and S237C. Kinetic parameters analysis revealed that S237G, S237A, S237H and S237D displayed improved kcat/Km toward 1a. Various prochiral ketones, including acetophenone, 4-chloroacetophenone and ethyl 2-oxo-4-phenylbutyrate could be asymmetrically reduced by S237C, S237G and S237E with > 99% e.e. This study provides guidance for the application of KpADH in the preparation of chiral secondary alcohols.
- Wang, Yue,Dai, Wei,Liu, Yongmei,Zhang, Zhongwei,Zhou, Jieyu,Xu, Guochao,Ni, Ye
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- Hydrogenation of Ketones on Dispersed Chiral-Modified Palladium Nanoparticles
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Hydrogenation of acetophenone and esters of ketoacids with molecular hydrogen in the presence of the Pd(acac)2-cinchonidine–H2 catalytic system has been studied. The dependence of the molar ratio of (–)-cinchonidine/Pd on size and shape of palladium nanoparticles, formed in the system, also on reaction rate and enantioselectivity has been established. The nature of the regularities observed for the Pd(acac)2-cinchonidine–H2 catalytic system was discussed.
- Nindakova,Strakhov,Kolesnikov
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p. 199 - 207
(2018/03/26)
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- Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin
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t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.
- Gong, Xu-Min,Zheng, Gao-Wei,Liu, You-Yan,Xu, Jian-He
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supporting information
p. 1349 - 1354
(2017/09/23)
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- Asymmetric transfer hydrogenation of aryl ketoesters with a chiral double-chain surfactant-type catalyst in water
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A chiral double-chain surfactant-type ligand was designed and synthesized. The rhodium catalyst formed from the ligand can self-assemble into chiral vesicular aggregates in water, which was applied to the ATH of a broad range of aromatic ketoesters in neat water and gave up to 99% yield and 99% ee. In addition, this double-chain surfactant-type catalyst could also be applied to the dynamic kinetic resolution (DKR) of bicyclic β-ketoesters in water.
- Li, Jiahong,Lin, Zechao,Huang, Qingfei,Wang, Qiwei,Tang, Lei,Zhu, Jin,Deng, Jingen
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supporting information
p. 5367 - 5370
(2017/11/22)
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- Preparation of structurally diverse chiral alcohols by engineering ketoreductase CgKR1
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Ketoreductases are tools for the synthesis of chiral alcohols in industry. However, the low activity of natural enzymes often restricts their use in industrial applications. On the basis of computational analysis and previous reports, two residues (F92 and F94) probably affecting the activity of ketoreductase CgKR1 were identified. By tuning these two residues, the CgKR1-F92C/F94W variant was obtained that exhibited higher activity toward all 28 structurally diverse substrates examined than the wild-type enzyme. Among them, 13 substrates have a specific activity over 50 U mg-1 (54-775 U mg-1). Using CgKR1-F92C/F94W as a catalyst, five substrates at high loading (>100 g-1 L-1) were reduced completely in gramscale preparative reactions. This approach provides accesses to pharmaceutically relevant chiral alcohols with high enantioselectivity (up to 99.0% ee) and high space-time yield (up to 583 g-1 L-1 day-1). Molecular dynamics simulations highlighted the crucial role of residues 92 and 94 in activity improvement. Our findings provide useful guidance for engineering other ketoreductases, especially those possessing a similar active pocket to that in CgKR1.
- Zheng, Gaowei,Liu, Yuan-Yang,Chen, Qi,Huang, Lei,Yu, Hui-Lei,Lou, Wen-Yong,Li, Chun-Xiu,Bai, Yun-Peng,Li, Ai-Tao,Xu, Jian-He
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p. 7174 - 7181
(2017/11/06)
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- A thermoregulated phase-separable chiral Pt nanocatalyst for recyclable asymmetric hydrogenation of α-ketoesters
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The design and preparation of a chiral Pt nanocatalyst system possessing thermoregulated phase-separation property and its application in recyclable asymmetric hydrogenation of α-ketoesters are presented.
- Xue, Xiuru,Wang, Yanhua,Han, Fu-She
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supporting information
p. 3346 - 3349
(2017/03/22)
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- Synthetically useful variants of industrial lipases from: Burkholderia cepacia and Pseudomonas fluorescens
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Industrial enzymes lipase PS (LPS) and lipase AK (LAK), which originate from Burkholderia cepacia and Pseudomonas fluorescens, respectively, are synthetically useful biocatalysts. To strengthen their catalytic performances, we introduced two mutations into hot spots of the active sites (residues 287 and 290). The LPS-L287F/I290A double mutant showed high catalytic activity and enantioselectivity for poor substrates for which the wild-type enzyme showed very low activity. The LAK-V287F/I290A double mutant was also an excellent biocatalyst with expanded substrate scope, which was comparable to the LPS-L287F/I290A double mutant. Thermodynamic parameters were determined to address the origin of the high enantioselectivity of the double mutant. The ΔΔH? term, but not the ΔΔS? term, was predominant, which suggests that the enantioselectivity is driven by a differential energy associated with intermolecular interactions around Phe287 and Ala290. A remarkable solvent effect was observed, giving a bell-shaped profile between the E values and the log&P or ? values of solvents with the highest E value in i-Pr2O. This suggests that an organic solvent with appropriate hydrophobicity and polarity provides the double mutant with some flexibility that is essential for excellent catalytic performance.
- Yoshida, Kazunori,Ono, Masakazu,Yamamoto, Takahiro,Utsumi, Takashi,Koikeda, Satoshi,Ema, Tadashi
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supporting information
p. 8713 - 8719
(2017/11/03)
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- Catalyst-Controlled Multicomponent Aziridination of Chiral Aldehydes
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A highly diastereoselective and enantioselective method for the multicomponent aziridination of chiral aldehydes has been developed with BOROX catalysts of the VANOL (3,3′-diphenyl-2,2′-bi-1-naphthol) and VAPOL (2,2′-diphenyl-(4-biphenanthrol)) ligands. Very high to perfect catalyst control is observed with most all substrates examined including aldehydes with chiral centers in the α- and β-positions. High catalyst control was also observed for a number of chiral heterocyclic aldehydes allowing for the preparation of epoxy aziridines, bis(aziridines) and ethylene diaziridines. Application of this reaction in the synthesis of β3-homo-d-alloisoleucine and β3-homo-l-isoleucine is reported.
- Mukherjee, Munmun,Zhou, Yubai,Dai, Yijing,Gupta, AniL K.,Pulgam, V. Reddy,Staples, Richard J.,Wulff, William D.
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supporting information
p. 2552 - 2556
(2017/03/06)
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- Stereoselective reduction of aromatic ketones by a new ketoreductase from Pichia glucozyma
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A new NADPH-dependent benzil reductase (KRED1-Pglu) was identified from the genome of the non-conventional yeast Pichia glucozyma CBS 5766 and overexpressed in E. coli. The new protein was characterised and reaction parameters were optimised for the enantioselective reduction of benzil to (S)-benzoin. A thorough study of the substrate range of KRED1-Pglu was conducted; in contrast to most other known ketoreductases, KRED1-Pglu prefers space-demanding substrates, which are often converted with high stereoselectivity. A molecular modelling study was carried out for understanding the structural determinants involved in the stereorecognition experimentally observed and unpredictable on the basis of steric properties of the substrates. As a result, a new useful catalyst was identified, enabling the enantioselective preparation of different aromatic alcohols and hydroxyketones.
- Contente, Martina Letizia,Serra, Immacolata,Brambilla, Marta,Eberini, Ivano,Gianazza, Elisabetta,De Vitis, Valerio,Molinari, Francesco,Zambelli, Paolo,Romano, Diego
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p. 193 - 201
(2016/01/09)
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- Synthesis of Planar Chiral Shvo Catalysts for Asymmetric Transfer Hydrogenation
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A new type of planar chiral Shvo catalysts, where the chirality is based solely on different substitution flanking the C￡O function, was prepared and used for transfer hydrogenation of imines and ketones. The reduction of ketimines represented by N-(1-phe
- Dou, Xiaowei,Hayashi, Tamio
-
supporting information
p. 1054 - 1058
(2016/04/19)
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- Dual pathway for the asymmetric transfer hydrogenation of α-ketoimides to chiral α-hydroxy imides or chiral α-hydroxy esters
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In an enantioselective reaction, we expect to obtain two types of chiral products through a controllable strategy in asymmetric catalysis. Herein, we develop Ru-catalysed asymmetric transfer hydrogenation of α-ketoimides to realise an enantioselective construction of chiral α-hydroxy imides or chiral α-hydroxy esters. The transformation of α-ketoimides catalysed by (S,S)-[RuCl(η6-mesitylene)diamine] can afford various chiral α-hydroxy imides with high yields and enantioselectivities, whereas that catalysed by (S,S)-[RuCl(η6-hexamethylbenzene)diamine] gives the desirable chiral α-hydroxy esters through a slight adjustment of the reaction conditions. The method described here is a controllable organic transformation with sodium formate as a hydrogen source under mild reaction conditions, and the benefit of this transformation is that various chiral α-hydroxy imides or α-hydroxy esters can be obtained selectively from α-ketoimides. Selective directive: An enantioselective transformation in the Ru-catalyzed asymmetric transfer hydrogenation of α-ketoimides to chiral α-hydroxy imides or α-hydroxy esters is developed. The transformation of α-ketoimides catalyzed by (S,S)-[RuCl(η6-mesitylene)diamine] can afford various chiral α-hydroxy imides with high yields and enantioselectivities, whereas that catalyzed by (S,S)-[RuCl(η6-hexamethylbenzene)diamine] give desirable chiral α-hydroxy esters through a slight adjustment of reaction conditions.
- Zhao, Qiankun,Zhao, Yuxi,Liao, Hang,Cheng, Tanyu,Liu, Guohua
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p. 412 - 416
(2016/02/05)
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- Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water
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A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity. (Chemical Equation Presented).
- Lin, Zechao,Li, Jiahong,Huang, Qingfei,Huang, Qiuya,Wang, Qiwei,Tang, Lei,Gong, Deying,Yang, Jun,Zhu, Jin,Deng, Jingen
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p. 4419 - 4429
(2015/05/13)
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- Synthesis of a P-stereogenic PNPtBu,Ph ruthenium pincer complex and its application in asymmetric reduction of ketones
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A novel P-stereogenic PNPtBu,Ph ruthenium complex has been synthesized and characterized enabling the asymmetric hydrogenation of a wide range of aromatic ketones with excellent catalytic activities (up to 98% conversion) and good levels of enantiodiscrimination (up to 95% ee). P-stereogenic PNPtBu,Ph Ru complex was for the first time synthesized and characterized and has proven to be an efficient catalyst for the asymmetric reduction of a wide range of ketones
- Arenas, Ismael,Boutureira, Omar,Matheu, M. Isabel,Díaz, Yolanda,Castillón, Sergio
-
supporting information
p. 3666 - 3669
(2015/06/16)
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- Chiral N,N′-dioxide-FeCl3 complex-catalyzed asymmetric intramolecular Cannizzaro reaction
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An environmentally benign catalyst, the N,N′-dioxide-FeCl3 complex, has been developed for the asymmetric intramolecular Cannizzaro reaction. Aryl and alkyl glyoxal monohydrates were applied to obtain α-hydroxy acid esters with excellent results. Deuterium-label and control experiments shed light on the reaction mechanism.
- Wu, Wangbin,Liu, Xiaohua,Zhang, Yuheng,Ji, Jie,Huang, Tianyu,Lin, Lili,Feng, Xiaoming
-
supporting information
p. 11646 - 11649
(2015/07/15)
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- Enantio- and chemoselective Br?nsted-acid/Mg(nBu) 2 catalysed reduction of α-keto esters with catecholborane
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The first enantio- and chemoselective Br?nsted-acid catalysed reduction of α-keto esters with catecholborane has been developed. The α-hydroxy esters were obtained under mild reaction conditions in virtually quantitative yields and excellent enantioselectivities. With slight modifications both enantiomers can be obtained without any loss of selectivity. This journal is the Partner Organisations 2014.
- Enders, Dieter,St?ckel, Bianca A.,Rembiak, Andreas
-
supporting information
p. 4489 - 4491
(2014/04/17)
-
- Entrapment of alkaloids within silver: From enantioselective hydrogenation to chiral recognition
-
An alkaloid@Ag composite was prepared for the first time and used as a cathode for the enantioselective hydrogenation. Excellent yield and a remarkable enantiomeric excess value were obtained under mild conditions. Moreover, alkaloid@Ag after extraction w
- Yang, Hengpan,Chi, Dinghui,Sun, Qilong,Sun, Wenwen,Wang, Huan,Lu, Jiaxing
-
supporting information
p. 8868 - 8870
(2014/08/05)
-
- A new class of tunable dendritic diphosphine ligands: Synthesis and applications in the Ru-catalyzed asymmetric hydrogenation of functionalized ketones
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A series of tunable G0-G3 dendritic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) ligands was prepared by attaching polyaryl ether dendrons onto the four phenyl rings on the P atoms. Their ruthenium complexes were employed in the asymmetric hydrogenation of β-ketoesters, α-ketoesters, and α-ketoamides to reveal the effects of dendron size on the catalytic properties. The second- and third-generation catalysts exhibited excellent enantioselectivities, which are remarkably higher than those obtained from the small molecular catalysts and the first-generation catalyst. Molecular modeling indicates that the incorporation of bulky dendritic wedges can influence the steric environments around the metal center. In addition, the ruthenium catalyst bearing a second-generation dendritic ligand could be recycled and reused seven times without any obvious decrease in enantioselectivity.
- Ma, Baode,Miao, Tingting,Sun, Yihua,He, Yanmei,Liu, Ji,Feng, Yu,Chen, Hui,Fan, Qing-Hua
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supporting information
p. 9969 - 9978
(2014/08/18)
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- Altering the substrate specificity of reductase CgKR1 from Candida glabrata by protein engineering for bioreduction of aromatic α-keto esters
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A versatile keto ester reductase CgKR1, exhibiting a broad substrate spectrum, was obtained from Candida glabrata by genome data mining. It showed the highest activity toward an aliphatic β-keto ester, ethyl 4-chloro-3-oxobutanoate (COBE), but much lower activity toward bulkier α-keto esters with an aromatic group, such as methyl ortho- chlorobenzoylformate (CBFM) and ethyl 2-oxo-4-phenylbutyrate (OPBE). By rational design of the active pocket, the substrate specificity of the reductase was significantly altered and this tailor-made reductase showed a much higher activity toward aromatic α-keto esters (～7-fold increase in k cat/Km toward CBFM) and lower activity toward aliphatic keto esters (～12-fold decrease in kcat/Km toward COBE). Meanwhile, the thermostability of the reductase was enhanced by a consensus approach. Such improvements may yield practical catalysts for the asymmetric bioreduction of these aromatic α-keto esters
- Huang, Lei,Ma, Hong-Min,Yu, Hui-Lei,Xu, Jian-He
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p. 1943 - 1948
(2014/07/07)
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- Aromatic cation activation: Nucleophilic substitution of alcohols and carboxylic acids
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A new method for the nucleophilic substitution of alcohols and carboxylic acids using aromatic tropylium cation activation has been developed. This article reports the use of chloro tropylium chloride for the rapid generation of alkyl halides and acyl chlorides under very mild reaction conditions. It demonstrates, for the first time, the synthetic potential of tropylium cations in promoting chemical transformations.
- Nguyen, Thanh V.,Bekensir, Alp
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p. 1720 - 1723
(2014/04/17)
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- Kinetic resolution of mandelate esters via stereoselective acylation catalyzed by lipase PS-30
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By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.
- Chen, Peiran,Yang, Wenhong
-
supporting information
p. 2290 - 2294
(2014/04/17)
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- Asymmetric catalytic arylation of ethyl glyoxylate using organoboron reagents and Rh(i)-phosphane and phosphane-phosphite catalysts
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Herein we report the first application of Rh(i)-phosphane and phosphane-phosphite catalysts in the enantioselective catalytic arylation of ethyl glyoxylate with organoboron reagents, providing access to ethyl mandelate derivatives in high yield (up to 99%) and moderate to very good enantioselectivities (up to 75% ee). Commercial phosphane ligands, such as (R)-MonoPhos and (R)-Phanephos were tested, as well as non-commercial (R,R)-TADDOL-derived phosphane-phosphite ligands. Those ligands containing bulky substituents in the ortho-and para-positions of the chiral phosphite moiety were found to be the most selective.
- Marques, Carolina Silva,Dindaroglu, Mehmet,Schmalz, Hans-Guenther,Burke, Anthony J.
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p. 6035 - 6041
(2014/01/23)
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- CHIRAL SPIRO-PYRIDYLAMIDOPHOSPHINE LIGAND COMPOUND, SYNTHESIS METHOD THEREFOR AND APPLICATION THEREOF
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The present invention relates to a chiral spiro-pyridylamidophosphine ligand compound, synthesis method therefor and application thereof. The chiral spiro-pyridylamidophosphine compound is a compound having a structure of Formula (I), a racemate or optical isomer thereof, or a catalytically acceptable salt thereof, and is mainly characterized by having a chiral spiro-dihydro-indene skeleton in its structure. The chiral spiro-pyridylamidophosphine compound may be synthesized with optical active 7-diaryl/alkylphosphino-7'-amino-1,1'-spiro-dihydro-indene or substituted 7-diaryl/alkylphosphino-7'-amino-1,1'-spiro-dihydro-indene having a spiro-skeleton as chiral starting material. The chiral spiro-pyridylamidophosphine compound may be used as a chiral ligand in asymmetric hydrogenation of a carbonyl compound catalyzed by iridium, in which the reaction activity is very high, the amount of the catalyst may be 0.0001 mol%, and the enantioselectivity of the reaction is up to 99.9%ee.
- -
-
Paragraph 0059; 0060
(2013/10/08)
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- Highly enantioselective double reduction of phenylglyoxal to (R)-1-phenyl-1,2-ethanediol by one NADPH-dependent yeast carbonyl reductase with a broad substrate profile
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The activity and enantioselectivity of a carbonyl reductase from Pichia pastoris GS115 were evaluated with a series of carbonyl compounds including aryl aldehydes, ketones, α- and β-ketoesters. This recombinant enzyme possessed a broad substrate profile with the ability of reducing both aldehydes and ketones. Especially, the enzyme catalyzed the double reduction of phenylglyoxal to (R)-1-phenyl-1,2-ethanediol with 99% yield and 99% ee by coupling with d-glucose dehydrogenase for the regeneration of cofactor NADPH, representing the first example of effective reduction of both aldehyde and ketone functional groups in one molecule by using only one enzyme. Furthermore, this study provides valuable information for guiding the future application of this versatile biocatalyst.
- Li, Zhe,Liu, Weidong,Chen, Xi,Jia, Shiru,Wu, Qiaqiang,Zhu, Dunming,Ma, Yanhe
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p. 3561 - 3564
(2013/04/24)
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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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- Stereospecific reduction of methyl o-chlorobenzoylformate at 300 g·L-1 without additional cofactor using a carbonyl reductase mined from Candida glabrata
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In order to search for oxidoreductases suitable for the preparation of methyl (R)-o-chloromandelate [(R)-CMM], the key intermediate for clopidogrel, the homologous proteins of Gre2p were expressed in Escherichia coli, among which CgKR1 showed the most satisfactory activity and stereoselectivity towards methyl o-chlorobenzoylformate (CBFM). Using the crude enzyme of CgKR1 and glucose dehydrogenase (GDH), as much as 300 g·L-1 of CBFM was almost stoichiometrically converted to (R)-CMM with excellent enantiomeric excess (98.7% ee). More importantly, the reaction could be performed without external addition of an expensive cofactor. The substrate profile indicates that keto esters serve as the most suitable substrate, which was confirmed by gram-scale preparations. Homology modeling and docking analysis revealed the molecular basis for the high stereoselectivity of CgKR1. These demonstrate not only the feasibility of in silico mining of novel enzymes based on sequence homology but also the applicability of this new reductase for the practical production of optically active (R)-CMM. Copyright
- Ma, Hongmin,Yang, Linlin,Ni, Yan,Zhang, Jie,Li, Chun-Xiu,Zheng, Gao-Wei,Yang, Huaiyu,Xu, Jian-He
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experimental part
p. 1765 - 1772
(2012/08/08)
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- Asymmetric addition of arylboronic acids to glyoxylate catalyzed by a ruthenium/Me-BIPAM complex
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The enantioselective synthesis of α-hydroxy esters by ruthenium-catalyzed 1,2-addition of arylboronic acids to tert-butyl glyoxylate is described. The use of RuCl2(PPh3)3 with (R,R)-Me-BIPAM gave optically active mandelic acids of up to 99% ee. Addition of a fluoride salt such as potassium fluoride (KF) or caesium fluoride (CsF) was effective for achieving high enantioselectivities. The Royal Society of Chemistry 2012.
- Yamamoto, Yasunori,Shirai, Tomohiko,Miyaura, Norio
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scheme or table
p. 2803 - 2805
(2012/04/23)
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- A new dehydrogenase from Clostridium acetobutylicum for asymmetric synthesis: Dynamic reductive kinetic resolution entry into the Taxotere side chain
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An NADP-dependent alcohol dehydrogenase from Clostridium acetobutylicum (CaADH) has been expressed and characterized. CaADH enantioselectively reduces aromatic α-, β- and γ-keto esters to the corresponding d-hydroxy esters and provides a building block for the Taxotere side chain (95% yield, 95% de, 99% ee) by dynamic reductive kinetic resolution (DYRKR).
- Applegate, Gregory A.,Cheloha, Ross W.,Nelson, David L.,Berkowitz, David B.
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supporting information; experimental part
p. 2420 - 2422
(2011/04/15)
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- A mild ligand-free iron-catalyzed liberation of alcohols from allylcarbonates
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Different from most carbonates the allyloxy carbonyl protecting group can be cleaved under neutral conditions using metal catalysis. However, most of the catalysts employed to date are based upon precious metals. Herein we present two protocols for the mild Fe-catalyzed liberation of alcohols from allylcarbonates that are characterized by broad functional group tolerance and exclusive chemoselectivity.
- Dieskau, Andre P.,Plietker, Bernd
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supporting information; experimental part
p. 5544 - 5547
(2011/12/05)
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- Asymmetric aerobic oxidation of α-hydroxy acid derivatives catalyzed by reusable, polystyrene-supported chiral N-salicylidene oxidovanadium tert-leucinates
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The direct immobilization of two different C-5-propargyl ether-modified, chiral N-salicylidene vanadyl(V) tert-leucinates onto 4-azidomethyl-substituted polystyrene by click chemistry was examined. Among the eight different solvents investigated, the resulting polystyrene-supported catalysts promote the asymmetric, aerobic oxidation of α-hydroxy (thio)esters and amides with enantioselectivities of up to 99% ee (selectivity factor up to 41) in chloroform. These polystyrene-supported catalysts can be readily recovered by filtration and reused for at least four consecutive runs without discernible loss of reactivity and enantioselectivity.
- Salunke, Santosh B.,Babu, N.Seshu,Chen, Chien-Tien
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supporting information; experimental part
p. 1234 - 1240
(2011/06/26)
-
- Enantioselective ketoester reductions in water: A comparison between microorganism-and ruthenium-catalyzed reactions
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In the search for green chemistry methods for the enantioselective reduction of ketoesters Saccharomyces cerevisiae-and ruthenium-catalyzed reactions in water have been investigated. The highest enantiomeric excesses for the reduction of α-and β-ketoesters have been obtained by S. cerevisiae. Chiral ruthenium catalysts are active for the reduction of all ketoesters with low to moderate enantioselectivities depending on the nature of the substrate and ligand. Interestingly, for several substrates both enantiomers of the hydroxyesters have been obtained according either to the catalytic method or to the structure of the ligand.
- Zeror, Saoussen,Collin, Jacqueline,Fiaud, Jean-Claude,Zouioueche, Louisa Aribi
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experimental part
p. 1211 - 1215
(2010/10/20)
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