Tadashi Ema

Carbazole-based BODIPYs with ethynyl substituents at the boron center: solid-state excimer fluorescence in the VIS/NIR region

Co-reporter:Chihiro Maeda;Keiji Nagahata

Organic & Biomolecular Chemistry 2017 vol. 15(Issue 37) pp:7783-7788

Publication Date(Web):2017/09/26

DOI:10.1039/C7OB01473B

Carbazole-based BODIPYs 1–6 with several different substituents at the boron atom site were synthesized. These dyes fluoresced in the solid state, and 3a with phenylethynyl groups exhibited a red-shifted and broad fluorescence spectrum, which suggested an excimer emission. Its derivatives 3b–n were synthesized, and the relationship between the solid-state emission and crystal packing was investigated. The X-ray crystal structures revealed cofacial dimers that might form excimers. From the structural optimization results, we found that the introduction of mesityl groups hindered intermolecular access and led to reduced interactions between the dimers. In addition, the red-shifted excimer fluorescence suppressed self-absorption, and dyes with ethynyl groups showed solid-state fluorescence in the vis/NIR region.

Synthetically useful variants of industrial lipases from Burkholderia cepacia and Pseudomonas fluorescens

Co-reporter:Kazunori Yoshida;Masakazu Ono;Takahiro Yamamoto;Takashi Utsumi;Satoshi Koikeda

Organic & Biomolecular Chemistry 2017 vol. 15(Issue 41) pp:8713-8719

Publication Date(Web):2017/10/25

DOI:10.1039/C7OB01823A

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 ε 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.

Synthesis of carbazole-based BODIPY dimers showing red fluorescence in the solid state

Co-reporter:Chihiro Maeda;Takumi Todaka;Tomomi Ueda

Organic & Biomolecular Chemistry 2017 vol. 15(Issue 44) pp:9283-9287

Publication Date(Web):2017/11/15

DOI:10.1039/C7OB02419C

Carbazole-based BODIPY dimers 2a–g were synthesized via direct arylation. They showed red-shifted solid-state fluorescence spectra as compared with the corresponding monomer. In addition, unsymmetrical dimers 2d, 2f, and 2g with two different substituents showed red fluorescence with improved quantum yields in the solid state.

Determination of enantiomeric excess of carboxylates by fluorescent macrocyclic sensors

Co-reporter:Ali Akdeniz, Tsuyoshi Minami, Sagiri Watanabe, Maki Yokoyama, Tadashi Ema and Pavel Anzenbacher

Chemical Science 2016 vol. 7(Issue 3) pp:2016-2022

Publication Date(Web):14 Dec 2015

DOI:10.1039/C5SC04235F

Chiral fluorescent chemosensors featuring macrocycles comprising BINOL auxiliary and an array of hydrogen bond donors were synthesized. To enhance fluorescence of the chemosensors, conjugated moieties were attached to the 3,3′-positions of the BINOL auxiliary. The resulting chemosensors recognize a number of carboxylates, namely, enantiomers of ibuprofen, ketoprofen, 2-phenylpropanoate, mandelate, and phenylalanine in a stereoselective fashion. Depending on the structure of the chemosensor, the presence of carboxylate yields fluorescence quenching or amplification. This information-rich signal can be used to determine the identity of the analyte including the sense of chirality. Quantitative experiments were performed aimed at analysis of enantiomeric excess of chiral carboxylates. The quantitative analysis of enantiomeric composition of ibuprofen, ketoprofen, and phenylalanine shows that the sensors correctly identify mixtures with varying enantiomeric excess and correctly predict the enantiomeric excess of unknown samples with error of prediction <1.6%.

Solvent-Free Benzoin and Stetter Reactions with a Small Amount of NHC Catalyst in the Liquid or Semisolid State

Co-reporter:Tadashi Ema, Yoshiko Nanjo, Sho Shiratori, Yuta Terao, and Ryo Kimura

Organic Letters 2016 Volume 18(Issue 21) pp:5764-5767

Publication Date(Web):October 25, 2016

DOI:10.1021/acs.orglett.6b03115

The intermolecular or intramolecular asymmetric benzoin reaction was catalyzed by a small amount of N-heterocyclic carbene (NHC) (0.2–1 mol %) under solvent-free conditions. The solvent-free intramolecular asymmetric Stetter reaction also proceeded efficiently with NHC (0.2–1 mol %). In some cases, even solid-to-solid or solid-to-liquid conversions took place with low catalyst loading (0.2–1 mol %).

Intramolecular Electronic Coupling in the Thiophene-Bridged Carbazole-Based Diporphyrin

Co-reporter:Chihiro Maeda, Mototsugu Takata, Asami Honsho, and Tadashi Ema

Organic Letters 2016 Volume 18(Issue 23) pp:6070-6073

Publication Date(Web):November 16, 2016

DOI:10.1021/acs.orglett.6b03054

The Glaser coupling reaction of ethynyl-substituted carbazole-based isophlorins provided butadiyne-bridged dimers, which were transformed into the thiophene-bridged dimers via the annulation reaction. Oxidation of these isophlorin dimers afforded carbazole-based diporphyrins. Notable electronic interactions in the diporphyrins have been confirmed by means of UV/vis–near-infrared (NIR) absorption spectroscopy, cyclic voltammetry (CV) measurements, and density functional theory (DFT) calculations.

Carbazole-Based Boron Dipyrromethenes (BODIPYs): Facile Synthesis, Structures, and Fine-Tunable Optical Properties

Co-reporter:Chihiro Maeda, Takumi Todaka, and Tadashi Ema

Organic Letters 2015 Volume 17(Issue 12) pp:3090-3093

Publication Date(Web):June 8, 2015

DOI:10.1021/acs.orglett.5b01363

Carbazole-based BODIPYs were synthesized in three steps using an organometallic approach consisting of sequential Ir-catalyzed borylation, Suzuki–Miyaura coupling, and boron complexation. Various substituents were introduced into the carbazole moiety, and large substituent effects were confirmed by means of absorption spectroscopy, cyclic voltammetry, and DFT calculations. Dibenzocarbazoles were also converted into the corresponding BODIPYs.

Quaternary ammonium hydroxide as a metal-free and halogen-free catalyst for the synthesis of cyclic carbonates from epoxides and carbon dioxide

Co-reporter:Tadashi Ema, Kazuki Fukuhara, Takashi Sakai, Masaki Ohbo, Fu-Quan Bai and Jun-ya Hasegawa

Catalysis Science & Technology 2015 vol. 5(Issue 4) pp:2314-2321

Publication Date(Web):03 Feb 2015

DOI:10.1039/C5CY00020C

Tetrabutylammonium hydroxide (TBAH) and other quaternary ammonium hydroxides catalyzed the cycloaddition of CO2 to epoxides under solvent-free conditions to give cyclic carbonates. When TBAH was exposed to CO2, TBAH was converted into tetrabutylammonium bicarbonate (TBABC), which was a catalytically active species. A D-labeled epoxide and an optically active epoxide were used to study the reaction mechanism, which invoked three plausible pathways. Among them, path A seemed to be predominant; the bicarbonate ion of TBABC attacks the less hindered C atom of the epoxide to generate a ring-opened alkoxide intermediate, which adds to CO2 to give a carbonate ion, and the subsequent cyclization yields a cyclic carbonate. Density functional theory (DFT) calculations successfully delineated the potential energy profile for each reaction pathway, among which path A was the lowest-energy pathway in accordance with the experimental results. The tetrabutylammonium (TBA) cation carries the positive charges on the H atoms, but not on the central N atom, and the positively charged H atoms close to the central N atom form an anion-binding site capable of stabilizing various anionic transition states and intermediates.

Bifunctional Catalysts Based on m-Phenylene-Bridged Porphyrin Dimer and Trimer Platforms: Synthesis of Cyclic Carbonates from Carbon Dioxide and Epoxides

Co-reporter:Dr. Chihiro Maeda;Tomoya Taniguchi;Kanae Ogawa ;Dr. Tadashi Ema

Angewandte Chemie International Edition 2015 Volume 54( Issue 1) pp:134-138

Publication Date(Web):

DOI:10.1002/anie.201409729

Abstract

Highly active bifunctional diporphyrin and triporphyrin catalysts were synthesized through Stille coupling reactions. As compared with a porphyrin monomer, both exhibited improved catalytic activities for the reaction of CO₂ with epoxides to form cyclic carbonates, because of the multiple catalytic sites which cooperatively activate the epoxide. Catalytic activities were carefully investigated by controlling temperature, reaction time, and catalyst loading, and very high turnover number and turnover frequency were obtained: 220 000 and 46 000 h⁻¹, respectively, for the magnesium catalyst, and 310 000 and 40 000 h⁻¹, respectively, for the zinc catalyst. Results obtained with a zinc/free-base hybrid diporphyrin catalyst demonstrated that the Br⁻ ions on the adjacent porphyrin moiety also function as nucleophiles.

Bifunctional Porphyrin Catalysts for the Synthesis of Cyclic Carbonates from Epoxides and CO2: Structural Optimization and Mechanistic Study

Co-reporter:Tadashi Ema ; Yuki Miyazaki ; Junta Shimonishi ; Chihiro Maeda ;Jun-ya Hasegawa

Journal of the American Chemical Society 2014 Volume 136(Issue 43) pp:15270-15279

Publication Date(Web):September 30, 2014

DOI:10.1021/ja507665a

We prepared bifunctional MgII porphyrin catalysts 1 for the solvent-free synthesis of cyclic carbonates from epoxides and CO2. The activities of 1d, 1h, and 1i, which have Br–, Cl–, and I– counteranions, respectively, increased in the order 1i < 1h < 1d. Catalysts 1d and 1j–m, which bear four tetraalkylammonium bromide groups with different alkyl chain lengths, showed comparable but slightly different activities. Based on the excellent catalyst 1d, we synthesized MgII porphyrin 1o with eight tetraalkylammonium bromide groups, which showed even higher catalytic activity (turnover number, 138,000; turnover frequency, 19,000 h–1). The catalytic mechanism was studied by using 1d. The yields were nearly constant at initial CO2 pressures in the 1–6 MPa range, suggesting that CO2 was not involved in the rate-determining step in this pressure range. No reaction proceeded in supercritical CO2, probably because the epoxide (into which the catalyst dissolved) dissolved in and was diluted by the supercritical CO2. Experiments with 18O-labeled CO2 and D-labeled epoxide suggested that the catalytic cycle involved initial nucleophilic attack of Br– on the less hindered side of the epoxide to generate an oxyanion, which underwent CO2 insertion to afford a CO2 adduct; subsequent intramolecular ring closure formed the cyclic carbonate and regenerated the catalyst. Density functional theory calculations gave results consistent with the experimental results, revealing that the quaternary ammonium cation underwent conformational changes that stabilized various anionic species generated during the catalytic cycle. The high activity of 1d and 1o was due to the cooperative action of the MgII and Br– and a conformational change (induced-fit) of the quaternary ammonium cation.

Selective Anion Sensing by Chiral Macrocyclic Receptors with Multiple Hydrogen-Bonding Sites

Co-reporter:Tadashi Ema, Keiichi Okuda, Sagiri Watanabe, Takayuki Yamasaki, Tsuyoshi Minami, Nina A. Esipenko, and Pavel Anzenbacher Jr.

Organic Letters 2014 Volume 16(Issue 5) pp:1302-1305

Publication Date(Web):February 14, 2014

DOI:10.1021/ol403643d

Chiral macrocycles featuring sulfonamide and/or amide groups as anion-binding sites were synthesized. X-ray crystal structures and DFT calculations have shown that they adopt different conformations that may lead to unique binding behavior. Indeed, various anions could be sensed by their colorimetric and/or fluorescence signal output. The chiral macrocycles showed chiral recognition for chiral anions. Furthermore, a multisensor array with two or four chiral receptors discriminated seven phosphate anions (AMP, ADP, ATP, CMP, GMP, Pi, and PPi) with 100% classification accuracy.

Recent progress in catalytic conversions of carbon dioxide

Co-reporter:Chihiro Maeda, Yuki Miyazaki and Tadashi Ema

Catalysis Science & Technology 2014 vol. 4(Issue 6) pp:1482-1497

Publication Date(Web):12 Feb 2014

DOI:10.1039/C3CY00993A

Chemical fixation of carbon dioxide (CO2), which is an inexpensive and renewable carbon source, is becoming more and more important. The development of both new reactions and new catalysts is needed to overcome the kinetic and thermodynamic stability of CO2. Organic and metal catalysts with unique and excellent activity and selectivity have been developed for various chemical conversions of CO2. In this perspective, we provide an overview of the recent progress in this field, classifying it into several categories, where each research is concisely summarized one by one using a single reaction scheme, a representative catalyst structure, and/or a catalytic cycle.

Synergistic effect of quaternary ammonium hydroxide and crown ether on the rapid and clear dissolution of cellulose at room temperature

Co-reporter:Tadashi Ema, Takuzo Komiyama, Satomi Sunami and Takashi Sakai

RSC Advances 2014 vol. 4(Issue 5) pp:2523-2525

Publication Date(Web):09 Dec 2013

DOI:10.1039/C3RA45888A

The simultaneous addition of 40% tetrabutylammonium hydroxide (TBAH) and crown ether (18-crown-6) promptly produced a clear aqueous solution of cellulose (10 wt%) at room temperature.

Robust porphyrin catalysts immobilized on biogenous iron oxide for the repetitive conversions of epoxides and CO2 into cyclic carbonates

Co-reporter:Tadashi Ema, Yuki Miyazaki, Tomoya Taniguchi and Jun Takada

Green Chemistry 2013 vol. 15(Issue 9) pp:2485-2492

Publication Date(Web):18 Jul 2013

DOI:10.1039/C3GC41055B

Metalloporphyrins were immobilized on biogenous iron oxide (BIO) produced by iron-oxidizing bacteria, Leptothrix ochracea. These organic–inorganic hybrid materials were used as immobilized catalysts for the synthesis of cyclic carbonates from epoxides and CO2 under solvent-free conditions. ZnII porphyrin immobilized via four tetraalkylammonium bromide groups showed high catalytic activity and reusability at a catalyst loading of 0.1 mol%. The product was obtained in 99% yield after nine times reuse, and the substrate scope was broad.

A bifunctional catalyst for carbon dioxide fixation: cooperative double activation of epoxides for the synthesis of cyclic carbonates

Co-reporter:Tadashi Ema, Yuki Miyazaki, Shohei Koyama, Yuya Yano and Takashi Sakai

Chemical Communications 2012 vol. 48(Issue 37) pp:4489-4491

Publication Date(Web):30 Mar 2012

DOI:10.1039/C2CC30591G

We have developed a very active bifunctional porphyrin catalyst showing a high turnover number (TON = 103000) for the synthesis of cyclic carbonates from CO2 and epoxides under solvent-free conditions.

Construction of Contiguous Tetrasubstituted Carbon Stereocenters by Intramolecular Crossed Benzoin Reactions Catalyzed by N-Heterocyclic Carbene (NHC) Organocatalyst

Co-reporter:Tadashi Ema;Kumiko Akihara;Ryoko Obayashi ;Takashi Sakai

Advanced Synthesis & Catalysis 2012 Volume 354( Issue 17) pp:3283-3290

Publication Date(Web):

DOI:10.1002/adsc.201200499

Abstract

Bicyclic compounds with two contiguous tetrasubstituted carbon stereocenters at bridgehead positions were synthesized by N-heterocyclic carbene (NHC)-catalyzed intramolecular crossed benzoin reactions of symmetrical compounds. This desymmetrization strategy was applied to asymmetric synthesis with chiral NHC organocatalysts. Transition-state models were proposed to explain the enantioselectivity. A tricyclic compound with three contiguous tetrasubstituted carbon stereocenters was synthesized by a stepwise strategy. The molecular structure and absolute configuration of the (+)-enantiomer of this tricyclic compound were determined by X-ray crystallographic analysis.

Redesign of enzyme for improving catalytic activity and enantioselectivity toward poor substrates: manipulation of the transition state

Co-reporter:Tadashi Ema, Yasuko Nakano, Daiki Yoshida, Shusuke Kamata and Takashi Sakai

Organic & Biomolecular Chemistry 2012 vol. 10(Issue 31) pp:6299-6308

Publication Date(Web):18 Jun 2012

DOI:10.1039/C2OB25614B

Secondary alcohols having bulky substituents on both sides of the hydroxy group are inherently poor substrates for most lipases. In view of this weakness, we redesigned a Burkholderia cepacia lipase to create a variant with improved enzymatic characteristics. The I287F/I290A double mutant showed a high conversion and a high E value (>200) for a poor substrate for which the wild-type enzyme showed a low conversion and a low E value (5). This enhancement of catalytic activity and enantioselectivity of the variant resulted from the cooperative action of two mutations: Phe287 contributed to both enhancement of the (R)-enantiomer reactivity and suppression of the (S)-enantiomer reactivity, while Ala290 created a space to facilitate the acylation of the (R)-enantiomer. The kinetic constants indicated that the mutations effectively altered the transition state. Substrate mapping analysis strongly suggested that the CH/π interaction partly enhanced the (R)-enantiomer reactivity, the estimated energy of the CH/π interaction being −0.4 kcal mol−1. The substrate scope of the I287F/I290A double mutant was broad. This biocatalyst was useful for the dynamic kinetic resolution of a variety of bulky secondary alcohols for which the wild-type enzyme shows little or no activity.

Synthetic macrocyclic receptors in chiral analysis and separation

Co-reporter:Tadashi Ema

Journal of Inclusion Phenomena and Macrocyclic Chemistry 2012 Volume 74( Issue 1-4) pp:41-55

Publication Date(Web):2012 December

DOI:10.1007/s10847-012-0136-6

Chiral synthetic macrocyclic receptors that can achieve chiral discrimination by NMR spectroscopy and/or chiral separation by HPLC are overviewed. Synthetic macrocycles introduced here include crown ethers, calixarenes/calixresorcinarenes/calixpyrroles, macrocyclic amides/amines, and porphyrins. These macrocyclic frameworks are advantageous because intermolecular interactions can take place effectively, such as the ion–dipole interactions in crown ethers, the CH/π and π–π interactions in calixarenes, hydrogen bonding and salt formation in macrocyclic amides and amines, and π–π stacking and metal coordination in porphyrins. Additional functional groups on the periphery of the macrocyclic platforms not only make the whole molecule chiral but also act as the interaction sites. Chiral macrocyclic receptors can show a high degree of chiral recognition/discrimination by using the peripheral functional groups as well as the macrocyclic skeletons (preorganization). Both hosts and guests are shown in the figures to quickly overview the molecular recognition scope of synthetic macrocyclic receptors in chiral analysis and separation.

Highly active lipase immobilized on biogenous iron oxidevia an organic bridging group: the dramatic effect of the immobilization support on enzymatic function

Co-reporter:Tadashi Ema, Yuki Miyazaki, Izumi Kozuki, Takashi Sakai, Hideki Hashimoto and Jun Takada

Green Chemistry 2011 vol. 13(Issue 11) pp:3187-3195

Publication Date(Web):10 Oct 2011

DOI:10.1039/C1GC15877E

Iron-oxidizing bacteria, Leptothrix ochracea, produce biogenous iron oxide (BIO), while the heat treatment of BIO gives its magnetized material (m-BIO). In this study, they were chemically modified with silane coupling agents to give organic–inorganic hybrid materials, which were then used as immobilization supports for enzymes. BIO-M, which was prepared by modifying BIO with 3-methacryloxypropyltrimethoxysilane, was found to be the best immobilization support. The immobilized lipases showed remarkably high catalytic activity; for example, Burkholderia cepacialipase (BCL) immobilized on BIO-M showed a turnover frequency of 33000 h−1 for 1-phenylethanol (1a). m-BIO-M, which was prepared by modifying m-BIO with 3-methacryloxypropyltrimethoxysilane, was also used as an immobilization support. Although the lipases immobilized on m-BIO-M showed lower catalytic activity than those immobilized on BIO-M, the former could be separated and reused easily by using a magnet. These immobilized enzymes could be recycled at least five times and are environmentally benign biocatalysts.

Chiral porphyrin dimer with a macrocyclic cavity for intercalation of aromatic guests

Co-reporter:Tadashi Ema, Norichika Ura, Katsuya Eguchi, Yuhei Ise and Takashi Sakai

Chemical Communications 2011 vol. 47(Issue 21) pp:6090-6092

Publication Date(Web):11 Apr 2011

DOI:10.1039/C1CC11572C

Chiral diporphyrin receptor 1, which has a macrocyclic cavity to sandwich aromatic guest molecules via double π–π stacking interactions, enabled the naked-eye detection of an aromatic explosive as well as chiral discrimination in NMR.

Rational creation of mutant enzyme showing remarkable enhancement of catalytic activity and enantioselectivity toward poor substrates

Co-reporter:Tadashi Ema, Shusuke Kamata, Masahiro Takeda, Yasuko Nakano and Takashi Sakai

Chemical Communications 2010 vol. 46(Issue 30) pp:5440-5442

Publication Date(Web):09 Apr 2010

DOI:10.1039/C001561J

Catalytic activity and enantioselectivity of lipase toward poor substrates bearing bulky substituents on both sides have been dramatically improved by rational design; the E value for a poor substrate was increased from 5 (wild-type enzyme) to >200 (I287F/I290A double mutant) with an acceleration of the reaction rate.

Chemical modification of biogenous iron oxide to create an excellent enzyme scaffold

Co-reporter:Takashi Sakai, Yuki Miyazaki, Ai Murakami, Noriko Sakamoto, Tadashi Ema, Hideki Hashimoto, Mitsuaki Furutani, Makoto Nakanishi, Tatsuo Fujii and Jun Takada

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 2) pp:336-338

Publication Date(Web):19 Oct 2009

DOI:10.1039/B919497E

The biogenous iron oxide (BIO) from Leptothrix ochracea was transformed to an organic–inorganic hybrid support to prepare an excellent immobilized enzyme showing high catalytic performance.

Stereoselective Synthesis of Bicyclic Tertiary Alcohols with Quaternary Stereocenters via Intramolecular Crossed Benzoin Reactions Catalyzed by N-Heterocyclic Carbenes

Co-reporter:Tadashi Ema, Yoshitaka Oue, Kumiko Akihara, Yuki Miyazaki and Takashi Sakai

Organic Letters 2009 Volume 11(Issue 21) pp:4866-4869

Publication Date(Web):October 1, 2009

DOI:10.1021/ol9019293

Bicyclic tertiary alcohols 1 bearing quaternary stereocenters at the two adjacent bridgehead positions were synthesized with high stereoselectivity via the intramolecular crossed benzoin reactions catalyzed by NHC organocatalysts.

Empirical method for predicting enantioselectivity in catalytic reactions: demonstration with lipase and oxazaborolidine

Co-reporter:Tadashi Ema, Norichika Ura, Masataka Yoshii, Toshinobu Korenaga, Takashi Sakai

Tetrahedron 2009 65(46) pp: 9583-9591

Publication Date(Web):

DOI:10.1016/j.tet.2009.09.058

Biomimetic trifunctional organocatalyst showing a great acceleration for the transesterification between vinyl ester and alcohol

Co-reporter:Tadashi Ema, Daisuke Tanida, Tatsuya Matsukawa and Takashi Sakai

Chemical Communications 2008 (Issue 8) pp:957-959

Publication Date(Web):22 Jan 2008

DOI:10.1039/B718763G

Trifunctional organocatalysts 1a and 1b mimicking the active site of serine hydrolases showed high catalytic activity with up to a 3 700 000-fold acceleration for the acyl-transfer reactions from vinyl trifluoroacetate to alcohol.

Highly Efficient Chemoenzymatic Synthesis of Methyl (R)-o-Chloromandelate, a Key Intermediate for Clopidogrel, via Asymmetric Reduction with Recombinant Escherichia coli

Co-reporter:Tadashi Ema;Sayaka Ide;Nobuyasu Okita ;Takashi Sakai

Advanced Synthesis & Catalysis 2008 Volume 350( Issue 13) pp:2039-2044

Publication Date(Web):

DOI:10.1002/adsc.200800292

Abstract

Methyl (R)-o-chloromandelate [(R)-1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) with recombinant Escherichia coli overproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the whole-cell reduction of 2, and the optimum productivity as high as 178 g/L was attained at 20 °C on a 2-g scale (1.0 M). The optimized reaction could be scaled up easily to transform 20 g of 2 in 100 mL of buffer. Three synthetic methods for 2 are compared.

Highly enantioselective and efficient synthesis of methyl (R)-o-chloromandelate with recombinant E. coli: toward practical and green access to clopidogrel

Co-reporter:Tadashi Ema, Nobuyasu Okita, Sayaka Ide and Takashi Sakai

Organic & Biomolecular Chemistry 2007 vol. 5(Issue 8) pp:1175-1176

Publication Date(Web):19 Mar 2007

DOI:10.1039/B703463F

Methyl (R)-o-chloromandelate ((R)-1), which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) (up to 1.0 M) with recombinant E. coli overproducing a versatile carbonyl reductase.

Rational control of enantioselectivity of lipase by site-directed mutagenesis based on the mechanism

Co-reporter:Tadashi Ema, Toshiyuki Fujii, Misa Ozaki, Toshinobu Korenaga and Takashi Sakai

Chemical Communications 2005 (Issue 37) pp:4650-4651

Publication Date(Web):12 Aug 2005

DOI:10.1039/B508244G

The enantioselectivity of a Burkholderia cepacia lipase toward secondary alcohols could be both increased and decreased rationally by introducing only a single mutation on the basis of the mechanism proposed previously.

Rational strategies for highly enantioselective lipase-catalyzed kinetic resolutions of very bulky chiral compounds: substrate design and high-temperature biocatalysis

Co-reporter:Tadashi Ema

Tetrahedron: Asymmetry 2004 Volume 15(Issue 18) pp:2765-2770

Publication Date(Web):20 September 2004

DOI:10.1016/j.tetasy.2004.06.055

Rational approaches to successful lipase-catalyzed kinetic resolutions of very bulky chiral compounds are briefly reviewed: substrate design and high-temperature biocatalysis. The molecular design based on a stereo-sensing mechanism was the key to the success in the kinetic resolution of 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin. The lipase-catalyzed transesterification of 1,1-diphenyl-2-propanol in n-decane proceeded with excellent enantioselectivity at high temperatures up to 120 °C in an autoclave.

Highly enantioselective lipase-catalyzed reactions at high temperatures up to 120°C in organic solvent

Co-reporter:Tadashi Ema, Masafumi Kageyama, Toshinobu Korenaga, Takashi Sakai

Tetrahedron: Asymmetry 2003 Volume 14(Issue 24) pp:3943-3947

Publication Date(Web):12 December 2003

DOI:10.1016/j.tetasy.2003.09.040

Lipase-catalyzed kinetic resolutions of 1,1-diphenyl-2-propanol were performed at high temperatures up to 120°C. Burkholderia cepacia lipase immobilized on porous ceramic particles, lipase PS-C II (Amano Enzyme Inc.), gave an enantiopure product at 40–120°C, with the highest conversion (39%) at 80–90°C. The mechanism of high enantioselectivity retained even at 120°C is also described briefly.Graphic(R)-1,1-Diphenyl-2-propyl acetateC17H18O2E.e. >98% (by HPLC)[α]14D=+44.2 (c 0.5, MeOH)Source of chirality: lipase resolutionAbsolute configuration: R(S)-1,1-Diphenyl-2-propanolC15H16OE.e.=58% (by HPLC)[α]18D=−28.6 (c 0.5, MeOH)Source of chirality: lipase resolutionAbsolute configuration: S(R)-1,2-Diphenylethyl acetateC16H16O2E.e.=66% (by HPLC)[α]15D=+14.0 (c 0.5, CHCl3)Source of chirality: lipase resolutionAbsolute configuration: R(S)-1,2-DiphenylethanolC14H14OE.e.=18% (by HPLC)[α]15D=+8.2 (c 0.5, MeOH)Source of chirality: lipase resolutionAbsolute configuration: S

Mechanism-based enzymatic method for reliable determination of absolute configuration of chiral 1-substituted ethanols: combination with NMR method

Co-reporter:Tadashi Ema, Masataka Yoshii, Toshinobu Korenaga, Takashi Sakai

Tetrahedron: Asymmetry 2002 Volume 13(Issue 11) pp:1223-1229

Publication Date(Web):21 June 2002

DOI:10.1016/S0957-4166(02)00318-X

It has been demonstrated that lipase is useful not only for kinetic resolution but also for the rapid determination of absolute configurations. We have previously proposed a mechanism represented by transition-state models to rationalize the enantioselectivity in the lipase- and subtilisin-catalyzed kinetic resolutions of secondary alcohols. The mechanism indicates that the enzyme-catalyzed reactions can be used as a tool for determining the absolute stereochemistry of secondary alcohols. In order to increase reliability, the enzymatic method was combined with Mosher's method using MTPA, to give a protocol which is named the double-confirmation method. The absolute configurations of six 1-substituted ethanols were determined consistently by this new procedure. The enzymatic method is quick, easy, economical, and reliable. An interesting similarity in conformation between the transition-state models and MTPA esters is also described.Graphic(S)-1-(3,5-Dibenzyloxyphenyl)ethanolC22H22O3E.e.=68% (by HPLC)[α]D26=−12.4 (c 1.00, CHCl3)Source of chirality: lipase resolutionAbsolute configuration: S(S)-1-(4-Benzyloxy-2-methoxy-3-methylphenyl)ethanolC17H20O3E.e.=43% (by HPLC)[α]D22=−11.1 (c 1.00, CHCl3)Source of chirality: lipase resolutionAbsolute configuration: S(S)-1-(4-(Imidazol-1-yl)phenyl)ethanolC11H12N2OE.e. >98% (by HPLC)[α]D17=−33 (c 0.48, CHCl3)Source of chirality: lipase resolutionAbsolute configuration: S

Chemoenzymatic synthesis of optically active alcohol and β-amino-acid derivative containing the difluoromethylene group

Co-reporter:Tadashi Ema, Taro Kadoya, Kumiko Akihara, Takashi Sakai

Journal of Molecular Catalysis B: Enzymatic (September 2010) Volume 66(Issues 1–2) pp:198-202

Publication Date(Web):1 September 2010

DOI:10.1016/j.molcatb.2010.05.009

The bioreduction of α,α-difluorinated ketones, ethyl 2,2-difluoro-3-oxobutanoate (2a) and 2,2-difluoro-1-phenyl-1,3-butanedione (2b), with cells of recombinant Escherichia coli overproducing SCR (Saccharomyces cerevisiae carbonyl reductase from bakers’ yeast) and GDH (glucose dehydrogenase from Bacillus megaterium) gave enantiomerically pure alcohols, ethyl (S)-2,2-difluoro-3-hydroxybutanoate ((S)-1a) and (S)-2,2-difluoro-3-hydroxy-1-phenyl-1-butanone ((S)-1b), respectively, in the presence of NADP+ and glucose in buffer. The reductions of 2a and 2b proceeded completely at the substrate concentrations of 0.4 M (67 g/L) and 1.0 M (200 g/L), respectively. The opposite enantiomers (R)-1a and (R)-1b were also produced by enzyme E039 (a mixture of carbonyl reductase and formate dehydrogenase) contained in Chiralscreen OH (Daicel Chemical Industries) in the presence of NADH and sodium formate in buffer. Enantiomerically pure (S)-1a was converted by organic synthetic methods into an α,α-difluorinated derivative of (R)-β-aminobutyric acid (BABA) in three steps.

Quaternary ammonium hydroxide as a metal-free and halogen-free catalyst for the synthesis of cyclic carbonates from epoxides and carbon dioxide

Co-reporter:Tadashi Ema, Kazuki Fukuhara, Takashi Sakai, Masaki Ohbo, Fu-Quan Bai and Jun-ya Hasegawa

Catalysis Science & Technology (2011-Present) 2015 - vol. 5(Issue 4) pp:NaN2321-2321

Publication Date(Web):2015/02/03

DOI:10.1039/C5CY00020C

Tetrabutylammonium hydroxide (TBAH) and other quaternary ammonium hydroxides catalyzed the cycloaddition of CO2 to epoxides under solvent-free conditions to give cyclic carbonates. When TBAH was exposed to CO2, TBAH was converted into tetrabutylammonium bicarbonate (TBABC), which was a catalytically active species. A D-labeled epoxide and an optically active epoxide were used to study the reaction mechanism, which invoked three plausible pathways. Among them, path A seemed to be predominant; the bicarbonate ion of TBABC attacks the less hindered C atom of the epoxide to generate a ring-opened alkoxide intermediate, which adds to CO2 to give a carbonate ion, and the subsequent cyclization yields a cyclic carbonate. Density functional theory (DFT) calculations successfully delineated the potential energy profile for each reaction pathway, among which path A was the lowest-energy pathway in accordance with the experimental results. The tetrabutylammonium (TBA) cation carries the positive charges on the H atoms, but not on the central N atom, and the positively charged H atoms close to the central N atom form an anion-binding site capable of stabilizing various anionic transition states and intermediates.

Determination of enantiomeric excess of carboxylates by fluorescent macrocyclic sensors

Co-reporter:Ali Akdeniz, Tsuyoshi Minami, Sagiri Watanabe, Maki Yokoyama, Tadashi Ema and Pavel Anzenbacher

Chemical Science (2010-Present) 2016 - vol. 7(Issue 3) pp:NaN2022-2022

Publication Date(Web):2015/12/14

DOI:10.1039/C5SC04235F

Chiral fluorescent chemosensors featuring macrocycles comprising BINOL auxiliary and an array of hydrogen bond donors were synthesized. To enhance fluorescence of the chemosensors, conjugated moieties were attached to the 3,3′-positions of the BINOL auxiliary. The resulting chemosensors recognize a number of carboxylates, namely, enantiomers of ibuprofen, ketoprofen, 2-phenylpropanoate, mandelate, and phenylalanine in a stereoselective fashion. Depending on the structure of the chemosensor, the presence of carboxylate yields fluorescence quenching or amplification. This information-rich signal can be used to determine the identity of the analyte including the sense of chirality. Quantitative experiments were performed aimed at analysis of enantiomeric excess of chiral carboxylates. The quantitative analysis of enantiomeric composition of ibuprofen, ketoprofen, and phenylalanine shows that the sensors correctly identify mixtures with varying enantiomeric excess and correctly predict the enantiomeric excess of unknown samples with error of prediction <1.6%.

Chiral porphyrin dimer with a macrocyclic cavity for intercalation of aromatic guests

Co-reporter:Tadashi Ema, Norichika Ura, Katsuya Eguchi, Yuhei Ise and Takashi Sakai

Chemical Communications 2011 - vol. 47(Issue 21) pp:NaN6092-6092

Publication Date(Web):2011/04/11

DOI:10.1039/C1CC11572C

Chiral diporphyrin receptor 1, which has a macrocyclic cavity to sandwich aromatic guest molecules via double π–π stacking interactions, enabled the naked-eye detection of an aromatic explosive as well as chiral discrimination in NMR.

Biomimetic trifunctional organocatalyst showing a great acceleration for the transesterification between vinyl ester and alcohol

Co-reporter:Tadashi Ema, Daisuke Tanida, Tatsuya Matsukawa and Takashi Sakai

Chemical Communications 2008(Issue 8) pp:NaN959-959

Publication Date(Web):2008/01/22

DOI:10.1039/B718763G

Trifunctional organocatalysts 1a and 1b mimicking the active site of serine hydrolases showed high catalytic activity with up to a 3 700 000-fold acceleration for the acyl-transfer reactions from vinyl trifluoroacetate to alcohol.

Highly enantioselective and efficient synthesis of methyl (R)-o-chloromandelate with recombinant E. coli: toward practical and green access to clopidogrel

Co-reporter:Tadashi Ema, Nobuyasu Okita, Sayaka Ide and Takashi Sakai

Organic & Biomolecular Chemistry 2007 - vol. 5(Issue 8) pp:NaN1176-1176

Publication Date(Web):2007/03/19

DOI:10.1039/B703463F

Methyl (R)-o-chloromandelate ((R)-1), which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) (up to 1.0 M) with recombinant E. coli overproducing a versatile carbonyl reductase.

Rational creation of mutant enzyme showing remarkable enhancement of catalytic activity and enantioselectivity toward poor substrates

Co-reporter:Tadashi Ema, Shusuke Kamata, Masahiro Takeda, Yasuko Nakano and Takashi Sakai

Chemical Communications 2010 - vol. 46(Issue 30) pp:NaN5442-5442

Publication Date(Web):2010/04/09

DOI:10.1039/C001561J

Catalytic activity and enantioselectivity of lipase toward poor substrates bearing bulky substituents on both sides have been dramatically improved by rational design; the E value for a poor substrate was increased from 5 (wild-type enzyme) to >200 (I287F/I290A double mutant) with an acceleration of the reaction rate.

Recent progress in catalytic conversions of carbon dioxide

Co-reporter:Chihiro Maeda, Yuki Miyazaki and Tadashi Ema

Catalysis Science & Technology (2011-Present) 2014 - vol. 4(Issue 6) pp:NaN1497-1497

Publication Date(Web):2014/02/12

DOI:10.1039/C3CY00993A

Chemical fixation of carbon dioxide (CO2), which is an inexpensive and renewable carbon source, is becoming more and more important. The development of both new reactions and new catalysts is needed to overcome the kinetic and thermodynamic stability of CO2. Organic and metal catalysts with unique and excellent activity and selectivity have been developed for various chemical conversions of CO2. In this perspective, we provide an overview of the recent progress in this field, classifying it into several categories, where each research is concisely summarized one by one using a single reaction scheme, a representative catalyst structure, and/or a catalytic cycle.

A bifunctional catalyst for carbon dioxide fixation: cooperative double activation of epoxides for the synthesis of cyclic carbonates

Co-reporter:Tadashi Ema, Yuki Miyazaki, Shohei Koyama, Yuya Yano and Takashi Sakai

Chemical Communications 2012 - vol. 48(Issue 37) pp:NaN4491-4491

Publication Date(Web):2012/03/30

DOI:10.1039/C2CC30591G

We have developed a very active bifunctional porphyrin catalyst showing a high turnover number (TON = 103000) for the synthesis of cyclic carbonates from CO2 and epoxides under solvent-free conditions.

Redesign of enzyme for improving catalytic activity and enantioselectivity toward poor substrates: manipulation of the transition state

Co-reporter:Tadashi Ema, Yasuko Nakano, Daiki Yoshida, Shusuke Kamata and Takashi Sakai

Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 31) pp:NaN6308-6308

Publication Date(Web):2012/06/18

DOI:10.1039/C2OB25614B

Secondary alcohols having bulky substituents on both sides of the hydroxy group are inherently poor substrates for most lipases. In view of this weakness, we redesigned a Burkholderia cepacia lipase to create a variant with improved enzymatic characteristics. The I287F/I290A double mutant showed a high conversion and a high E value (>200) for a poor substrate for which the wild-type enzyme showed a low conversion and a low E value (5). This enhancement of catalytic activity and enantioselectivity of the variant resulted from the cooperative action of two mutations: Phe287 contributed to both enhancement of the (R)-enantiomer reactivity and suppression of the (S)-enantiomer reactivity, while Ala290 created a space to facilitate the acylation of the (R)-enantiomer. The kinetic constants indicated that the mutations effectively altered the transition state. Substrate mapping analysis strongly suggested that the CH/π interaction partly enhanced the (R)-enantiomer reactivity, the estimated energy of the CH/π interaction being −0.4 kcal mol−1. The substrate scope of the I287F/I290A double mutant was broad. This biocatalyst was useful for the dynamic kinetic resolution of a variety of bulky secondary alcohols for which the wild-type enzyme shows little or no activity.

Chemical modification of biogenous iron oxide to create an excellent enzyme scaffold

Co-reporter:Takashi Sakai, Yuki Miyazaki, Ai Murakami, Noriko Sakamoto, Tadashi Ema, Hideki Hashimoto, Mitsuaki Furutani, Makoto Nakanishi, Tatsuo Fujii and Jun Takada

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 2) pp:NaN338-338

Publication Date(Web):2009/10/19

DOI:10.1039/B919497E

The biogenous iron oxide (BIO) from Leptothrix ochracea was transformed to an organic–inorganic hybrid support to prepare an excellent immobilized enzyme showing high catalytic performance.

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