2024/02/02 更新

写真a

エマ タダシ
依馬 正
EMA Tadashi
所属
環境生命自然科学学域 教授
職名
教授
外部リンク

学位

  • 博士(工学) ( 京都大学 )

研究キーワード

  • 有機合成化学・生物有機化学

学歴

  • 京都大学    

    1989年 - 1994年

      詳細を見る

    国名: 日本国

    researchmap

  • 京都大学   Faculty of Engineering  

    1985年 - 1989年

      詳細を見る

    国名: 日本国

    researchmap

経歴

  • 岡山大学 学術研究院環境生命自然科学学域 教授

    2023年 - 現在

      詳細を見る

  • 岡山大学 学術研究院自然科学学域 教授

    2021年 - 2023年

      詳細を見る

  • 岡山大学 大学院自然科学研究科 教授

    2012年 - 2021年

      詳細を見る

  • 岡山大学 大学院自然科学研究科 准教授

    2007年 - 2012年

      詳細を見る

  • 岡山大学 大学院自然科学研究科 助教授

    2005年 - 2007年

      詳細を見る

  • 岡山大学 工学部 助教授

    2002年 - 2005年

      詳細を見る

  • 岡山大学 工学部 助手

    1994年 - 2002年

      詳細を見る

▼全件表示

所属学協会

▼全件表示

委員歴

  • 有機合成化学協会   理事・中国四国支部長  

    2023年 - 現在   

      詳細を見る

  • ホスト-ゲスト・超分子化学研究会   幹事  

    2022年 - 現在   

      詳細を見る

    団体区分:学協会

    researchmap

  • 基礎有機化学会   理事  

    2022年 - 現在   

      詳細を見る

    団体区分:学協会

    researchmap

  • 有機合成化学協会   中国四国支部事務局(平成21年度〜令和3年度)(事務局代表 平成25年度〜令和元年度)  

    2009年   

      詳細を見る

    団体区分:学協会

    有機合成化学協会

    researchmap

  • 日本農芸化学会   中四国支部 評議員(平成17年度〜平成20年度、平成23年度〜平成24年度)  

    2008年   

      詳細を見る

    団体区分:学協会

    日本農芸化学会

    researchmap

  • 生体触媒化学研究会   幹事  

    2004年 - 現在   

      詳細を見る

    団体区分:学協会

    生体触媒化学研究会

    researchmap

  • 日本化学会   生体機能関連化学部会 幹事(平成15年度〜平成21年度) 同上 ニュースレター編集委員(平成16年度〜平成21年度)  

    1988年   

      詳細を見る

    団体区分:学協会

    日本化学会

    researchmap

▼全件表示

 

論文

  • Synthesis and Photophysical Properties of Dihetero[8]circulenes

    Chihiro Maeda, Koki Akiyama, Tadashi Ema

    Organic Letters   2023年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.orglett.3c01304

    researchmap

  • One‐Pot Synthesis of Aldehydes or Alcohols from CO 2 via Formamides or Silyl Formates

    Fan Yang, Yuta Saiki, Koichi Nakaoka, Tadashi Ema

    Advanced Synthesis & Catalysis   2023年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/adsc.202300031

    researchmap

  • One-Pot Synthesis of Dihydropyrans via CO2 Reduction and Domino Knoevenagel/oxa-Diels–Alder Reactions

    Kazuto Takaishi, Ritsuki Nishimura, Yuha Toda, Hajime Morishita, Tadashi Ema

    Organic Letters   2023年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.orglett.3c00047

    researchmap

  • Circularly polarized luminescence from porphyrin-containing (supra)molecular systems

    Chihiro Maeda, Issa Yasutomo, Kazuto Takaishi, Tadashi Ema

    Journal of Porphyrins and Phthalocyanines   27 ( 07n10 )   903 - 911   2023年2月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:World Scientific Pub Co Pte Ltd  

    Functional dyes showing circularly polarized luminescence (CPL) have attracted considerable attention. Porphyrins and porphyrinoids have characteristic properties useful for the development of CPL materials, although the examples of CPL-active porphyrins and porphyrinoids are still limited. Here we have summarized recent progress in CPL-active systems containing porphyrins or phthalocyanines, which are classified into the following four categories: (i) porphyrins with chiral sources; (ii) axially chiral porphyrin dimers; (iii) self-assembled porphyrins; (iv) porphyrin-sensitized CPL dyes.

    DOI: 10.1142/s108842462330001x

    researchmap

  • Circularly polarized luminescence in molecular recognition systems: Recent achievements

    Kazuto Takaishi, Chihiro Maeda, Tadashi Ema

    Chirality   35 ( 2 )   92 - 103   2023年2月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Abstract

    Circularly polarized luminescence (CPL) dyes are recognized to be new generation materials and have been actively developed. Molecular recognition systems provide nice approaches to novel CPL materials, such as stimuli‐responsive switches and chemical sensing materials. CPL may be induced simply by mixing chiral or achiral, luminescent or nonluminescent host and guest; there are several combinations. Molecular recognition can potentially save time and effort to construct well‐ordered chiral structures with noncovalent attractive interactions as compared with the multi‐step synthesis of covalently bonded dyes. It is a challenging subject to engage molecular recognition events with CPL, and it is important and interesting to see how it is achieved. In fact, simple molecular recognition systems can even enable the fine adjustment of CPL performance and detailed conformational/configurational analysis of the excited state. Here we overview the recent achievements of simple host–guest complexes capable of exhibiting CPL, summarizing concisely the host/guest structures, CPL intensities, and characteristics.

    DOI: 10.1002/chir.23522

    researchmap

    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/chir.23522

  • Cu-catalyzed carboxylation of organoboronic acid pinacol esters with CO2

    Chihiro Maeda, Takumi Cho, Ren Kumemoto, Tadashi Ema

    Organic & Biomolecular Chemistry   2023年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/D3OB00938F

    researchmap

  • Catalytic synthesis and physical properties of CO2-based cross-linked poly(cyclohexene carbonate)s

    Chihiro Maeda, Kenta Kawabata, Kaito Niki, Yuma Sako, Takumi Okihara, Tadashi Ema

    Polymer Chemistry   14 ( 37 )   4338 - 4343   2023年

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry (RSC)  

    Bifunctional aluminum porphyrins catalyzed the terpolymerization of cyclohexene oxide (CHO), bis(CHO), and CO2 to give cross-linked polycarbonates.

    DOI: 10.1039/D3PY00870C

    researchmap

  • Synthesis of Trimethylene Carbonates and Polycarbonates from Oxetanes and CO2 Using Bifunctional Aluminum Porphyrin Catalysts

    Chihiro Maeda, Hina Inoue, Ayano Ichiki, Takumi Okihara, Tadashi Ema

    ACS Catalysis   2022年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acscatal.2c03583

    researchmap

  • Mechanism of BPh3‐Catalyzed N‐Methylation of Amines with CO2 and Phenylsilane: Cooperative Activation of Hydrosilane

    Manussada Ratanasak, Takumi Murata, Taishin Adachi, Jun‐ya Hasegawa, Tadashi Ema

    Chemistry – A European Journal   2022年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/chem.202202210

    researchmap

    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/chem.202202210

  • Binaphthyl‐Bridged Pyrenophanes: Intense Circularly Polarized Luminescence Based on a D 2 Symmetry Strategy

    Kazuto Takaishi, Sho Murakami, Fumiya Yoshinami, Tadashi Ema

    Angewandte Chemie International Edition   2022年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/anie.202204609

    researchmap

  • Ruthenium Complexes Bearing Axially Chiral Bipyridyls: The Mismatched Diastereomer Showed Red Circularly Polarized Phosphorescence

    Kazuto Takaishi, Yusuke Nakatsuka, Hitomi Asano, Yuya Yamada, Tadashi Ema

    Chemistry – A European Journal   2022年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/chem.202104212

    researchmap

  • Deoxygenative CO2 conversions with triphenylborane and phenylsilane in the presence of secondary amines or nitrogen-containing aromatics

    Takumi Murata, Mahoko Hiyoshi, Shinsuke Maekawa, Yuta Saiki, Manussada Ratanasak, Jun-ya Hasegawa, Tadashi Ema

    Green Chemistry   24 ( 6 )   2385 - 2390   2022年

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry ({RSC})  

    DOI: 10.1039/D1GC04599G

    researchmap

  • Enhancement of protein thermostability by three consecutive mutations using loop-walking method and machine learning

    Kazunori Yoshida, Shun Kawai, Masaya Fujitani, Satoshi Koikeda, Ryuji Kato, Tadashi Ema

    Scientific Reports   11 ( 1 )   2021年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    We developed a method to improve protein thermostability, “loop-walking method”. Three consecutive positions in 12 loops of Burkholderia cepacia lipase were subjected to random mutagenesis to make 12 libraries. Screening allowed us to identify L7 as a hot-spot loop having an impact on thermostability, and the P233G/L234E/V235M mutant was found from 214 variants in the L7 library. Although a more excellent mutant might be discovered by screening all the 8000 P233X/L234X/V235X mutants, it was difficult to assay all of them. We therefore employed machine learning. Using thermostability data of the 214 mutants, a computational discrimination model was constructed to predict thermostability potentials. Among 7786 combinations ranked in silico, 20 promising candidates were selected and assayed. The P233D/L234P/V235S mutant retained 66% activity after heat treatment at 60 °C for 30 min, which was higher than those of the wild-type enzyme (5%) and the P233G/L234E/V235M mutant (35%).

    DOI: 10.1038/s41598-021-91339-4

    Scopus

    PubMed

    researchmap

  • Chiral exciplex dyes showing circularly polarized luminescence: Extension of the excimer chirality rule

    Kazuto Takaishi, Sho Murakami, Kazuhiro Iwachido, Tadashi Ema

    Chemical Science   12 ( 43 )   14570 - 14576   2021年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of axially chiral binaphthyls and quaternaphthyls possessing two kinds of aromatic fluorophores, such as pyrenyl, perylenyl, and 4-(dimethylamino)phenyl groups, arranged alternately were synthesized by a divergent method. In the excited state, the fluorophores selectively formed a unidirectionally twisted exciplex (excited heterodimer) by a cumulative steric effect and exhibited circularly polarized luminescence (CPL). They are the first examples of a monomolecular exciplex CPL dye. This versatile method for producing exciplex CPL dyes also improved fluorescence intensity, and the CPL properties were not very sensitive to the solvent or to the temperature owing to the conformationally rigid exciplex. This systematic study allowed us to confirm that the excimer chirality rule can be applied to the exciplex dyes: left- and right-handed exciplexes with a twist angle of less than 90° exhibit (-)- and (+)-CPL, respectively. This journal is

    DOI: 10.1039/d1sc04403f

    Scopus

    researchmap

  • Facile Synthesis of Azahelicenes and Diaza[8]circulenes through the Intramolecular Scholl Reaction

    Chihiro Maeda, Shuichi Nomoto, Koki Akiyama, Takayuki Tanaka, Tadashi Ema

    Chemistry - A European Journal   27 ( 63 )   15699 - 15705   2021年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Carbazole-based aza[7]helicenes and hetero[9]helicenes were successfully obtained via the intramolecular Scholl reaction of 3,6-bis(biphenyl-2-yl)carbazole congeners, while the reaction of 3,6-bis(naphthylphenyl)-appended carbazole gave a triple helicene via an unexpected simultaneous double aryl rearrangement. DFT calculations suggested that the rearrangement proceeded via an arenium cation intermediate. In addition, the reaction of methoxy-appended substrate gave an azahepta[8]circulene via the concurrent C−C bond formation. These helical dyes showed circularly polarized luminescence. The azahepta[8]circulene was further transformed into deeply saddle-distorted dibenzodiaza[8]circulenes as the first example of its solution-based synthesis and unambiguous structural determination.

    DOI: 10.1002/chem.202102269

    Scopus

    researchmap

  • C-Methylenation of anilines and indoles with CO<inf>2</inf>and hydrosilane using a pentanuclear zinc complex catalyst

    Kazuto Takaishi, Hiroyasu Kosugi, Ritsuki Nishimura, Yuya Yamada, Tadashi Ema

    Chemical Communications   57 ( 65 )   8083 - 8086   2021年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The one-stepC-methylenation of anilines and indoles with CO2and phenylsilane was catalyzed by a pentanuclear ZnIIcomplex to give diarylmethanesviageminal C-H and C-C bond formation. It is proposed that the zinc-hydride complex generatedin situis a catalytically active species and that bis(silyl)acetal is a key intermediate. When aniline was used as a substrate, both theC-methylenation andN-methylation proceeded.

    DOI: 10.1039/d1cc03675k

    Scopus

    PubMed

    researchmap

  • Circularly Polarized Luminescence Liquids Based on Siloxybinaphthyls: Best Binaphthyl Dihedral Angle in the Excited State

    Kazuto Takaishi, Tomoki Matsumoto, Miyu Kawataka, Tadashi Ema

    Angewandte Chemie - International Edition   60 ( 18 )   9968 - 9972   2021年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of axially chiral 1,1′-binaphthyls with trialkylsiloxy (OSiR3) groups were synthesized. Among them, 1 a–c possessing OSiR3 groups at the 7,7′-positions and methyl groups at the 2,2′-positions were liquids at room temperature, and the neat liquids showed circularly polarized luminescence (CPL) (R=Bu; Φfl,liquid=0.21, |glum,liquid|=1.6×10−3). The |glum,liquid| value is the highest of pure liquids. These compounds remained liquid over a broad range of temperatures, down to −50 °C. Time-dependent DFT calculations indicated that in the excited state, the binaphthyls adopt a transoid conformation with a small angle between the electric and magnetic transition dipole moments (θμ,m=77°), which is a key factor in their CPL activity. The best binaphthyl dihedral angle in the excited state is approximately 110°.

    DOI: 10.1002/anie.202101226

    Scopus

    PubMed

    researchmap

  • Synthesis and electronic properties of carbazole-based core-modified diporphyrins showing near infrared absorption

    Chihiro Maeda, Takuma Shirakawa, Tadashi Ema

    Chemical Communications   56 ( 95 )   15048 - 15051   2020年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Directly linked carbazole-based core-modified diporphyrin D2 and fused diporphyrin F2 were synthesized. These diporphyrins showed significant electronic interactions and conjugation allowing for redshifted near infrared (NIR) absorption and small HOMO-LUMO gaps as confirmed by NIR absorption spectroscopy, cyclic voltammetry (CV) measurements, and DFT calculations. This journal is

    DOI: 10.1039/d0cc06289h

    Scopus

    PubMed

    researchmap

  • Aggregation-Induced Circularly Polarized Luminescence from Boron Complexes with a Carbazolyl Schiff Base

    Chihiro Maeda, Shuichi Nomoto, Kazuto Takaishi, Tadashi Ema

    Chemistry - A European Journal   26 ( 57 )   13016 - 13021   2020年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A variety of carbazolyl-appended Schiff bases were readily synthesized from 1-formylcarbazoles and aniline derivatives. Boron complexation of the resulting ligands allowed for facile preparation of new carbazole-based BODIPY analogues showing solid-state fluorescence. Furthermore, some dyes were converted into chiral compounds through the Et2AlCl-mediated incorporation of a binaphthyl unit. The chiral dyes showed aggregation-induced fluorescence and circularly polarized luminescence (CPL) with the ΦF and glum of up to 0.22 and −3.5×10−3, respectively, in the solid state. The solid-state fluorescence and CPL were well characterized by the crystal packing analyses and DFT calculations.

    DOI: 10.1002/chem.202001463

    Scopus

    PubMed

    researchmap

  • Tetrameric and Hexameric Porphyrin Nanorings: Template Synthesis and Photophysical Properties

    Chihiro Maeda, Shoki Toyama, Naoki Okada, Kazuto Takaishi, Seongsoo Kang, Dongho Kim, Tadashi Ema

    Journal of the American Chemical Society   142 ( 37 )   15661 - 15666   2020年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Hexameric and tetrameric porphyrin nanorings, Z6T6 and Z4T4, were synthesized in 53% and 14% yields, respectively, by the Sonogashira-type self-oligomerization of porphyrin monomer 1 using hexadentate template T6 and tetrapyridylporphyrin template T4. Template-free nanorings Z6 and Z4 were also prepared. The femtosecond transient absorption measurements revealed fast excitation energy hopping (EEH) along these nanorings with hopping rates of 2-5 ps. Treatment of Z6 with chiral template CT6 gave Z6CT6 showing circular dichroism (CD) and circularly polarized luminescence (CPL) in the absorption and fluorescence regions of Z6, respectively, which indicates chirality transfer from CT6 to Z6.

    DOI: 10.1021/jacs.0c07707

    Scopus

    PubMed

    researchmap

  • Aluminum porphyrins with quaternary ammonium halides as catalysts for copolymerization of cyclohexene oxide and CO<inf>2</inf>: metal-ligand cooperative catalysis

    Jingyuan Deng, Manussada Ratanasak, Yuma Sako, Hideki Tokuda, Chihiro Maeda, Jun Ya Hasegawa, Kyoko Nozaki, Tadashi Ema

    Chemical Science   11 ( 22 )   5669 - 5675   2020年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bifunctional AlIIIporphyrins with quaternary ammonium halides,2-Cland2-Br, worked as excellent catalysts for the copolymerization of cyclohexene oxide (CHO) and CO2at 120 °C. Turnover frequency (TOF) and turnover number (TON) reached 10 000 h−1and 55 000, respectively, and poly(cyclohexene carbonate) (PCHC) with molecular weight of up to 281 000 was obtained with a catalyst loading of 0.001 mol%. In contrast, bifunctional MgIIand ZnIIcounterparts,3-Cland4-Cl, as well as a binary catalyst system,1-Clwith bis(triphenylphosphine)iminium chloride (PPNCl), showed poor catalytic performances. Kinetic studies revealed that the reaction rate was first-order in [CHO] and [2-Br] and zero-order in [CO2], and the activation parameters were determined: ΔH‡= 12.4 kcal mol−1, ΔS‡= −26.1 cal mol−1K−1, and ΔG‡= 21.6 kcal mol−1at 80 °C. Comparative DFT calculations on two model catalysts, AlIIIcomplex2′and MgIIcomplex3′, allowed us to extract key factors in the catalytic behavior of the bifunctional AlIIIcatalyst. The high polymerization activity and carbonate-linkage selectivity originate from the cooperative actions of the metal center and the quaternary ammonium cation, both of which facilitate the epoxide-ring opening by the carbonate anion to form the carbonate linkage in the key transition state such asTS3b(ΔH‡= 13.3 kcal mol−1, ΔS‡= −3.1 cal mol−1K−1, and ΔG‡= 14.4 kcal mol−1at 80 °C).

    DOI: 10.1039/d0sc01609h

    Scopus

    researchmap

  • Synthesis of silyl formates, formamides, and aldehydesviasolvent-free organocatalytic hydrosilylation of CO<inf>2</inf>

    Takumi Murata, Mahoko Hiyoshi, Manussada Ratanasak, Jun Ya Hasegawa, Tadashi Ema

    Chemical Communications   56 ( 43 )   5783 - 5786   2020年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Carbon dioxide (CO2) was used as a C1 source to prepare silyl formates, formamides, and aldehydes. Tetrabutylammonium acetate (TBAA) catalyzed the solvent-freeN-formylation of amines with CO2and hydrosilane to give formamides including Weinreb formamide, Me(MeO)NCHO, which was successively converted into aldehydes by one-pot reactions with Grignard reagents.

    DOI: 10.1039/d0cc01371d

    Scopus

    PubMed

    researchmap

  • Azahelicene-Fused BODIPY Analogues Showing Circularly Polarized Luminescence

    Chihiro Maeda, Keiji Nagahata, Takuma Shirakawa, Tadashi Ema

    Angewandte Chemie - International Edition   59 ( 20 )   7813 - 7817   2020年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Helical carbazole-based BODIPY analogues were readily synthesized via aza[7]helicenes. The structures of azahelicene-incorporated BF2 dyes were elucidated by x-ray diffraction analysis. DFT calculations revealed that the π-conjugated system expanded from the helicene moiety to the BODIPY framework. The azahelicene-fused boron complexes showed the Cotton effects and the circularly polarized luminescence (CPL) in the visible region. Furthermore, an axially chiral binaphthyl group was attached to the helically chiral dyes, which enhanced the chiroptical properties.

    DOI: 10.1002/anie.202001186

    Scopus

    PubMed

    researchmap

  • Minimization of Amounts of Catalyst and Solvent in NHC-Catalyzed Benzoin Reactions of Solid Aldehydes: Mechanistic Consideration of Solid-to-Solid Conversion and Total Synthesis of Isodarparvinol B

    Kenta Iwai, Masakazu Ono, Yoshiko Nanjo, Tadashi Ema

    ACS Omega   5 ( 17 )   10207 - 10216   2020年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Attempts were made to minimize the amounts of catalyst and solvent in the NHC-catalyzed benzoin reactions of solid aldehydes. In some case, solid-to-solid conversions proceeded in the solvent-free NHC-catalyzed benzoin reactions. Even if a mixture of the substrate, N-heterocyclic carbene (NHC) precursor, and inorganic base was initially a powdery solid, the reaction did proceed at reaction temperature lower than the melting points of each compound. The solid mixture partially melted or became a slurry or suspension in the meantime. We call this solid/liquid mixture a semisolid state. The reaction giving an optically active product was faster than that giving a racemic mixture of the same product. Melting-point depression was observed for a series of mixtures of the substrate and product in different substrate/product ratios. Solvent-free solid-to-solid conversions were accelerated by the formation of a semisolid state resulting from the melting-point depression of the solid substrate accompanied by the product formation. In the case of solid substrates with high melting points, melting-point depression was useless, and the addition of a small amount of solvent was needed. The first total synthesis of isodarparvinol B was achieved via the NHC-catalyzed intramolecular benzoin reaction using a small amount of solvent as an additive.

    DOI: 10.1021/acsomega.0c01141

    Scopus

    researchmap

  • Synthesis and Chiroptical Properties of Chiral Carbazole-Based BODIPYs

    Chihiro Maeda, Keita Suka, Keiji Nagahata, Kazuto Takaishi, Tadashi Ema

    Chemistry - A European Journal   26 ( 19 )   4261 - 4268   2020年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of carbazole-based boron dipyrromethenes (BODIPYs) 2 a–g bearing binaphthyl units have been synthesized by the Et2AlCl-mediated reaction of the corresponding BODIPY difluorides 1 a–g with 1,1′-binaphthalene-2,2′-diol. Substituents such as halogen, nitrile, and amino groups were tolerated under the reaction conditions, and the reaction of the phenylethynyl-substituted 1 h gave (R,R)-3 h bearing two binaphthyl units. The chiroptical properties of these dyes with different substituents were investigated by UV/Vis, CD, fluorescence, and circularly polarized luminescence (CPL) spectroscopy. The CD spectra showed Cotton effects in the absorption region of the BODIPY moieties. In addition, they showed CPL both in solution and in the solid state. Interestingly, several dyes recorded higher glum values in the solid state, probably due to intermolecular interactions. Because (R,R)-3 h recorded relatively low glum values, the diastereomer (R,S)-3 h was prepared. The (R,S) diastereomer showed intense CPL, which suggests a synergetic effect of the two binaphthyl groups. Finally, chiral carbazole-based BODIPY dimers have been synthesized for the first time and their chiroptical properties were investigated. They showed redshifted fluorescence and CPL, which reached the near-IR (NIR) region in the solid state.

    DOI: 10.1002/chem.201904954

    Scopus

    PubMed

    researchmap

  • Solvent-Induced Sign Inversion of Circularly Polarized Luminescence: Control of Excimer Chirality by Hydrogen Bonding

    Kazuto Takaishi, Kazuhiro Iwachido, Tadashi Ema

    Journal of the American Chemical Society   142 ( 4 )   1774 - 1779   2020年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of pyrenes sandwiched by axially chiral 1,1′-binaphthyls were synthesized. Among them, (R,R)-3 possessing 2-hydroxy-3,3′-dimethylbinaphthyls exhibited solvent-dependent inversion of the sign of circularly polarized luminescence (CPL) without a change in emission wavelength. The (-)- and (+)-CPL were detected in nonpolar and polar solvents, respectively, with glum values of -0.012 and +0.012. This switching property originates from the inversion of excimer chirality caused by the presence or absence of intermolecular hydrogen bonds in the excited state. The CPL intensity was also changed by variation of the temperature and concentration.

    DOI: 10.1021/jacs.9b13184

    Scopus

    PubMed

    researchmap

  • Chiral carbazole-based porphyrins showing absorption and circular dichroism in the near-infrared region

    Chihiro Maeda, Tadashi Ema

    Journal of Porphyrins and Phthalocyanines   24 ( 1-3 )   247 - 251   2020年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chiral carbazole-based porphyrins were synthesized for the first time via the incorporation of hydrobenzoin units at the thiophene moieties. They showed absorption and circular dichroism in the near-infrared (NIR) region. The NIR absorption was further red-shifted by solvent-induced aggregation.

    DOI: 10.1142/S1088424619500937

    Scopus

    researchmap

  • Axially Chiral peri-Xanthenoxanthenes as a Circularly Polarized Luminophore

    Kazuto Takaishi, Sakiko Hinoide, Tomoki Matsumoto, Tadashi Ema

    Journal of the American Chemical Society   141 ( 30 )   11852 - 11857   2019年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of axially chiral peri-xanthenoxanthenes (PXXs) were synthesized from 1,1′-bi-2-naphthol without optical resolution. These are the first examples of chiral PXXs. Among them, PXX 5 with two naphthalene rings connected via a methylenedioxy bridge and a chiral axis displayed intense fluorescence (FL) and circularly polarized luminescence (CPL) both in solution (φFL of 0.72 and |glum| of 1.4 × 10-3) and in the solid state (φFL of 0.13 and |glum| of 4.8 × 10-3). The bridged structure of PXX 5 adjusts the angle between the vectors of the electric and magnetic transition dipole moments, which is essential for showing intense CPL activity.

    DOI: 10.1021/jacs.9b06240

    Scopus

    PubMed

    researchmap

  • Unexpected Macrocyclic Multinuclear Zinc and Nickel Complexes that Function as Multitasking Catalysts for CO<inf>2</inf> Fixations

    Kazuto Takaishi, Bikash Dev Nath, Yuya Yamada, Hiroyasu Kosugi, Tadashi Ema

    Angewandte Chemie - International Edition   58 ( 29 )   9984 - 9988   2019年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Unique self-assembled macrocyclic multinuclear ZnII and NiII complexes with binaphthyl-bipyridyl ligands (L) were synthesized. X-ray analysis revealed that these complexes consisted of an outer ring (Zn3L3 or Ni3L3) and an inner core (Zn2 or Ni). In the ZnII complex, the inner Zn2 part rotated rapidly inside the outer ring in solution on an NMR timescale. These complexes exhibited dual catalytic activities for CO2 fixations: synthesis of cyclic carbonates from epoxides and CO2 and temperature-switched N-formylation/N-methylation of amines with CO2 and hydrosilane.

    DOI: 10.1002/anie.201904224

    Scopus

    PubMed

    researchmap

  • Evolving Fluorophores into Circularly Polarized Luminophores with a Chiral Naphthalene Tetramer: Proposal of Excimer Chirality Rule for Circularly Polarized Luminescence

    Kazuto Takaishi, Kazuhiro Iwachido, Ryosuke Takehana, Masanobu Uchiyama, Tadashi Ema

    Journal of the American Chemical Society   141 ( 15 )   6185 - 6190   2019年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A versatile method for converting various fluorescent polycyclic aromatic hydrocarbons into circularly polarized luminescence (CPL) excimer dyes with high glum and φFL values is reported. This method involves the functionalization of a chiral quaternaphthyl with six fluorophores via ester linkages in the last step of the synthesis. The usefulness of this approach was demonstrated for 1-, 2-, and 4-pyrenyl, 2- and 3-perylenyl, and 2-anthryl dyes. Most of them are the first or rare examples of CPL dyes. In the ground state, the fluorophores are tightly arranged by cumulative steric and electronic effects. In the excited state, the fluorophores form a twist excimer that maintains the ground-state conformations. The local chiral excimer directly affected the CPL properties. The systematic study on the signs of the CPLs allowed us to find a rule called the excimer chirality rule: right- and left-handed excimers exhibit (+)- and (-)-CPL, respectively.

    DOI: 10.1021/jacs.9b02582

    Scopus

    PubMed

    researchmap

  • Chiral Bifunctional Metalloporphyrin Catalysts for Kinetic Resolution of Epoxides with Carbon Dioxide

    Chihiro Maeda, Mayato Mitsuzane, Tadashi Ema

    Organic Letters   21 ( 6 )   1853 - 1856   2019年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chiral binaphthyl-strapped Zn(II) porphyrins with triazolium halide units were synthesized as bifunctional catalysts for kinetic resolution of epoxides with CO 2 . Several catalysts were screened by changing the linker length and nucleophilic counteranions, and the optimized catalyst accelerated the enantioselective reaction at ambient temperature to produce optically active cyclic carbonates and epoxides.

    DOI: 10.1021/acs.orglett.9b00447

    Scopus

    PubMed

    researchmap

  • Hemisquaramide Tweezers as Organocatalysts: Synthesis of Cyclic Carbonates from Epoxides and CO <inf>2</inf>

    Kazuto Takaishi, Takafumi Okuyama, Shota Kadosaki, Masanobu Uchiyama, Tadashi Ema

    Organic Letters   21 ( 5 )   1397 - 1401   2019年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Hemisquaramide tweezers, a new family of H-bond donor organocatalysts, are reported. The catalysts could be synthesized within two steps. Among them, H 8 -binaphthyl-linked hemisquaramide 7 markedly accelerated the synthesis of cyclic carbonates from epoxides and CO 2 . The reactions proceeded well under mild and solvent-free conditions. Kinetic resolution was also achieved at -20 °C (s = 3.0). The adjustable bite angle and orientation of the two NH groups of the catalysts are important for the high activity.

    DOI: 10.1021/acs.orglett.9b00117

    Scopus

    PubMed

    researchmap

  • Chiroptical and catalytic properties of doubly binaphthyl-strapped chiral porphyrins

    Chihiro Maeda, Kanae Ogawa, Kosuke Sadanaga, Kazuto Takaishi, Tadashi Ema

    Chemical Communications   55 ( 8 )   1064 - 1067   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Doubly (R)-binaphthyl-strapped porphyrins with methylene chains were synthesized. The CD spectra showed the positive Cotton effect around the Soret bands, and several porphyrins showed CPL. In addition, we found that the chiral porphyrins were applicable to kinetic resolution of epoxide with CO2.

    DOI: 10.1039/c8cc09114e

    Scopus

    PubMed

    researchmap

  • Synthesis of chiral carbazole-based BODIPYs showing circularly polarized luminescence

    Chihiro Maeda, Keiji Nagahata, Kazuto Takaishi, Tadashi Ema

    Chemical Communications   55 ( 21 )   3136 - 3139   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chiral carbazole-based BODIPYs with a binaphthyl unit were synthesized via an Al-mediated reaction. Et2AlCl was found to be a convenient reagent for the reaction to give the chiral BODIPYs in high yields. It has been shown for the first time that these chiral carbazole-based BODIPYs show circularly polarized luminescence (CPL) both in solution and in the solid state.

    DOI: 10.1039/c9cc00894b

    Scopus

    PubMed

    researchmap

  • Synthesis and electronic properties of π-expanded carbazole-based porphyrins

    Chihiro Maeda, Yumi Tanaka, Takuma Shirakawa, Tadashi Ema

    Chemical Communications   55 ( 68 )   10162 - 10165   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Peripheral π-expansion of carbazole-based porphyrins was achieved for the first time by the Pt-catalyzed cyclization and the incorporation of a benzocarbazole unit. These two types of fused porphyrins showed red-shifted and broad NIR absorption due to the expanded π-conjugation as confirmed by NIR absorption spectroscopy and DFT calculations.

    DOI: 10.1039/c9cc05079e

    Scopus

    PubMed

    researchmap

  • Cross-Coupling Approach to an Array of Macrocyclic Receptors Functioning as Chiral Solvating Agents

    Tadashi Ema, Takayuki Yamasaki, Sagiri Watanabe, Mahoko Hiyoshi, Kazuto Takaishi

    Journal of Organic Chemistry   83 ( 18 )   10762 - 10769   2018年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chiral macrocyclic receptors 1 with multiple hydrogen-bonding sites in the cavity were synthesized and used as NMR chiral solvating agents (CSAs). The Suzuki-Miyaura cross-coupling reaction gave rapid access to a series of variants 1b-p of unsubstituted parent compound 1a. Among them, 1d with the 4-cyanophenyl group at the 3,3′-positions of the binaphthyl moiety was the most excellent CSA for a benchmark analyte compound, 2-chloropropionic acid (CPA); both of the quartet and doublet signals of CPA were split most completely in CDCl3. Binding constants (Ka) determined in CDCl3 by NMR titrations indicated that (R)-1d was the most enantioselective (Ka(S)/Ka(R) = 5.4). Interestingly, the Ka value of (R)-1d for (S)-CPA (5900) was greater than that of (R)-1a for (S)-CPA (3080), which strongly suggests an attractive interaction between the 4-cyanophenyl group of (R)-1d and (S)-CPA. The X-ray crystal structure of 1d indicates that one of the two H atoms meta to the cyano group is directed toward the cavity. DFT calculations suggested that this H atom of the 4-cyanophenyl group of (R)-1d forms a weak hydrogen bond with the Cl atom of (S)-CPA (C-H···Cl-C hydrogen bond).

    DOI: 10.1021/acs.joc.8b01327

    Scopus

    PubMed

    researchmap

  • Binaphthyl-Bipyridyl cyclic dyads as a chiroptical switch

    Kazuto Takaishi, Makoto Yasui, Tadashi Ema

    Journal of the American Chemical Society   140 ( 16 )   5334 - 5338   2018年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad 2 bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |glum| of 1.6 × 10-3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer 4 exhibited a dextro/levo rotation switching ability in [α]D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes.

    DOI: 10.1021/jacs.8b01860

    Scopus

    PubMed

    researchmap

  • Calix[4]pyrroles as macrocyclic organocatalysts for the synthesis of cyclic carbonates from epoxides and carbon dioxide

    Chihiro Maeda, Sota Sasaki, Kazuto Takaishi, Tadashi Ema

    Catalysis Science and Technology   8 ( 16 )   4193 - 4198   2018年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Calix[4]pyrrole 1, calix[4]arene 2, or porphyrin 3 together with tetrabutylammonium iodide (TBAI) catalyzed the conversion of epoxides and CO2 into cyclic carbonates. Among them, meso-octamethylcalix[4]pyrrole 1a, which was synthesized easily in one step by the acid-catalyzed condensation of pyrrole with acetone, was found to be a very active and robust organocatalyst. DFT calculations suggested that 1a adopts a 1,3-alternate conformation to stabilize the anionic species generated during the catalysis. In the key transition state of the epoxide ring-opening step, one pyrrolic NH group and the tetrabutylammonium (TBA) cation activate the epoxide by hydrogen bonding while another NH group on the opposite side guides the I- anion, which is located away from the TBA cation, to the backside attack on the epoxide.

    DOI: 10.1039/c8cy00941d

    Scopus

    researchmap

  • Control of chiroptical properties of axially chiral naphthalene oligomers

    Kazuto Takaishi, Tadashi Ema

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   76 ( 9 )   885 - 893   2018年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    We developed several naphthalene oligomers with contiguous chiral axes as chiroptical dyes. RS-alternating oligomers with the 2, 2′-methylenedioxy bridges take a V-shaped conformation with a notably extensive conjugation in the rod direction, leading to high fluorescence in solution and in the solid state (ΦFL, solution = 0.64 and ΦFLsolid = 0.13 for an octamer). Theoretical studies indicated that the dihedral angles of naphthalene rings were held steady 48-49°, and both the HOMO and LUMO were spread throughout the molecule. It should be noted that the bridged R,R,R,R,R,R,R)-naphthalene octamer showed more intense fluorescence (FL) and circularly polarized luminescence (CPL) (ΦFL, solution = 0.90, g lum, solution = + 2.2 × 10-3, ΦFL, solid = 0.22, and g lum, solid = + 7.0 × 10-3). The high ΦFL and glum values were due to the rigidity. Moreover, the octamer molecules were incapable of forming efficiently stacked structures due to the non-planar conformation, which led to a high ΦFLsolid value in the solid state. A(R,R, R)-naphthalene tetramer possessing eight pyrenes displayed intense excimer-FL and CPL (ΦFLsolution = 0.25, glum, solution = + 0.034, ΦFL, solid = 0.28, and g lum, solid = +5.3 × 10-3). Pyrenes densely connected to a naphthalene tetramer via ester linkers were conformationally rigid with right-handed chirality and were important for obtaining strong CPL.

    DOI: 10.5059/yukigoseikyokaishi.76.885

    Scopus

    researchmap

  • Intense excimer CPL of pyrenes linked to a quaternaphthyl

    Kazuto Takaishi, Ryosuke Takehana, Tadashi Ema

    Chemical Communications   54 ( 12 )   1449 - 1452   2018年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (R,R,R)-Quaternaphthyls possessing eight and six pyrenes (compounds 4 and 3) displayed intense excimer-CPL. The glum values in solution and in the solid state were +0.034-0.037 and +0.0053-0.0056, respectively. The glum values of 3 and 4 were indistinguishable, indicating that the pyrenes of 3 and 4 assumed the same conformation, even in excited states. The intense CPL was caused by conformationally rigid pyrenes arranged via the cumulative steric effects along the quaternaphthyl axis.

    DOI: 10.1039/c7cc09187g

    Scopus

    PubMed

    researchmap

  • Palladium Complexes of Carbazole-Based Chalcogenaisophlorins: Synthesis, Structure, and Solid-State NIR Absorption Spectra

    Chihiro Maeda, Kazuto Takaishi, Tadashi Ema

    ChemPlusChem   82 ( 12 )   1368 - 1371   2017年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Annulation reactions of the butadiyne-bridged carbazole dimer 1 produced carbazole-based chalcogenaisophlorins 2–4, which were transformed into the corresponding palladium complexes 2Pd–4Pd. The structures were characterized by NMR spectroscopy and X-ray diffraction analysis. Metallation fixed the structures which displayed weak antiaromatic character derived from the 20π isophlorin framework. These complexes showed weak near-infrared (NIR) absorption typical for antiaromatic porphyrinoids in solution. In addition, 2Pd and 3Pd showed relatively strong solid-state NIR absorption. X-ray diffraction analyses of 2Pd and 3Pd revealed trimeric and dimeric stacked layered structures, respectively, and DFT calculations suggest that the solid-state NIR absorption is ascribed to intermolecular charge transfer.

    DOI: 10.1002/cplu.201700430

    Scopus

    PubMed

    researchmap

  • Spectroscopic Discrimination of Diastereomeric Complexes Involving an Axially Chiral Receptor

    Antonello Filippi, Caterina Fraschetti, Laura Guarcini, Costantino Zazza, Tadashi Ema, Maurizio Speranza

    ChemPhysChem   18 ( 18 )   2475 - 2481   2017年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The infrared multiphoton dissociation (IRMPD) spectra of electrospray ionization (ESI)-formed proton-bound complexes between the axially chiral multifunctional macrocycle MaR and d- and l-phenylalanine (PD and PL) or d- and l-3,4-dihydroxyphenylalanine (DD and DL) are recorded in the (Formula presented.) =2800–3700 cm−1 region. Whereas the diastereomeric [MaR⋅H⋅PD]+ and [MaR⋅H⋅PL]+ complexes do not show any significant spectral differences, the spectrum of [MaR⋅H⋅DD]+ clearly diverges from that of its [MaR⋅H⋅DL]+ diastereomer. A comparison of the experimental spectra with the B3LYP/6-31G**-calculated harmonic vibrational frequencies of a number of stable structures indicates the formation, in the ESI source, of very similar spectroscopically active structures, with the protonated amino acid placed outside the flat cavity of the macrocycle and hydrogen-bonded at its O2 center. Different spectral signatures of the [MaR⋅H⋅DD]+ and [MaR⋅H⋅DL]+ complexes are attributed to the coexistence of several stable rotamers in the ESI source.

    DOI: 10.1002/cphc.201700732

    Scopus

    PubMed

    researchmap

  • Chiral Macrocyclic Organocatalysts for Kinetic Resolution of Disubstituted Epoxides with Carbon Dioxide

    Tadashi Ema, Maki Yokoyama, Sagiri Watanabe, Sota Sasaki, Hiromi Ota, Kazuto Takaishi

    Organic Letters   19 ( 15 )   4070 - 4073   2017年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Among chiral macrocycles 1 synthesized, 1m with the 3,5-bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the enantioselective synthesis of cyclic carbonates from disubstituted or monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable for the enantioselective activation of epoxides. A catalytic cycle proposed was supported by DFT calculations.

    DOI: 10.1021/acs.orglett.7b01838

    Scopus

    PubMed

    researchmap

  • Helical Oligonaphthodioxepins Showing Intense Circularly Polarized Luminescence (CPL) in Solution and in the Solid State

    Kazuto Takaishi, Takahiro Yamamoto, Sakiko Hinoide, Tadashi Ema

    Chemistry - A European Journal   23 ( 39 )   9249 - 9252   2017年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A series of oligonaphthodioxepins was synthesized, revealing a helically arranged octamer, (R,R,R,R,R,R,R)-3, which showed intense circularly polarized luminescence (CPL) both in solution and in the solid state. The fluorescence quantum yields (ΦFL) in solution and in the solid state were 0.90 and 0.22, respectively, and the glum values in solution and in the solid state were +2.2×10−3 and +7.0×10−3, respectively. This is one of the highest solid-state CPL glum values yet reported. The high ΦFL and glum values were due to the rigidity, as well as to the fact that (R,R,R,R,R,R,R)-3 was a non-planar molecule. Moreover, (R,R,R,R,R,R,R)-3 was highly stable both chemically and stereochemically.

    DOI: 10.1002/chem.201702143

    Scopus

    PubMed

    researchmap

  • Magnetic Attachment of Lipase Immobilized on Bacteriogenic Iron Oxide Inside a Microtube Reactor for the Kinetic Resolution of Secondary Alcohols

    Kyoko Mandai, Takehiro Fukuda, Yuki Miyazaki, Hideki Hashimoto, Hiroki Mandai, Tadashi Ema, Jun Takada, Seiji Suga

    Synlett   28 ( 7 )   805 - 810   2017年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A PTFE microtube reactor was constructed with lipase immobilized on magnetized bacteriogenic iron oxide, which was retained inside of the tube by attraction to an external magnet. The reactor was used for the lipase-promoted kinetic resolution of secondary alcohols and gave sufficient catalytic activity, which was maintained during long-term flow over 14 days.

    DOI: 10.1055/s-0036-1589953

    Scopus

    researchmap

  • Electronic Tuning of Zinc Porphyrin Catalysts for the Conversion of Epoxides and Carbon Dioxide into Cyclic Carbonates

    Chihiro Maeda, Sota Sasaki, Tadashi Ema

    ChemCatChem   9 ( 6 )   946 - 949   2017年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bifunctional ZnII porphyrin catalysts bearing tributylammonium bromide groups at the meta positions of the meso-phenyl groups showed high catalytic activity for the synthesis of cyclic carbonates from epoxides and CO2. Herein, several substituents with different electronic properties were introduced at the para positions. Introduction of electron-donating groups decreased the catalytic activity, whereas the introduction of electron-withdrawing groups increased the activity. The substituents modulated the Lewis acidity of the zinc center, which was confirmed by binding constant experiments. The bifunctional catalyst bearing cyano groups showed the highest catalytic activity with a turnover frequency of up to 42 000 h−1.

    DOI: 10.1002/cctc.201601690

    Scopus

    researchmap

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

    Chihiro Maeda, Takumi Todaka, Tomomi Ueda, Tadashi Ema

    Organic and Biomolecular Chemistry   15 ( 44 )   9283 - 9287   2017年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1039/c7ob02419c

    Scopus

    PubMed

    researchmap

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

    Chihiro Maeda, Keiji Nagahata, Tadashi Ema

    Organic and Biomolecular Chemistry   15 ( 37 )   7783 - 7788   2017年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1039/c7ob01473b

    Scopus

    PubMed

    researchmap

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

    Kazunori Yoshida, Masakazu Ono, Takahiro Yamamoto, Takashi Utsumi, Satoshi Koikeda, Tadashi Ema

    Organic and Biomolecular Chemistry   15 ( 41 )   8713 - 8719   2017年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1039/c7ob01823a

    Scopus

    PubMed

    researchmap

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

    Chihiro Maeda, Mototsugu Takata, Asami Honsho, Tadashi Ema

    Organic Letters   18 ( 23 )   6070 - 6073   2016年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1021/acs.orglett.6b03054

    Scopus

    researchmap

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

    Tadashi Ema, Yoshiko Nanjo, Sho Shiratori, Yuta Terao, Ryo Kimura

    Organic Letters   18 ( 21 )   5764 - 5767   2016年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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 %).

    DOI: 10.1021/acs.orglett.6b03115

    Scopus

    researchmap

  • Theoretical Study on Highly Active Bifunctional Metalloporphyrin Catalysts for the Coupling Reaction of Epoxides with Carbon Dioxide

    Jun ya Hasegawa, Ray Miyazaki, Chihiro Maeda, Tadashi Ema

    Chemical Record   16 ( 5 )   2260 - 2267   2016年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Highly active bifunctional metalloporphyrin catalysts were developed for the coupling reaction of epoxides with CO2 to produce cyclic carbonates. The bifunctional catalysts have both quaternary ammonium halide groups and a metal center. To elucidate the roles of these catalytic groups, DFT calculations were performed. Control reactions using tetrabutylammonium halide as a catalyst were also investigated for comparison. In the present article, the results of our computational studies are overviewed. The computational results are consistent with the experimental data and are useful for elucidating the structure–activity relationship. The key features responsible for the high catalytic activity of the bifunctional catalysts are as follows: 1) the cooperative action of the halide anion (nucleophile) and the metal center (Lewis acid); 2) the near-attack conformation, leading to the efficient opening of the epoxide ring in the rate-determining step; and 3) the conformational change of the quaternary ammonium cation to stabilize various anionic species generated during catalysis, in addition to the robustness (thermostability) of the catalysts.

    DOI: 10.1002/tcr.201600053

    Scopus

    researchmap

  • Color-Tunable Solid-State Fluorescence Emission from Carbazole-Based BODIPYs

    Chihiro Maeda, Takumi Todaka, Tomomi Ueda, Tadashi Ema

    Chemistry - A European Journal   22 ( 22 )   7508 - 7513   2016年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Several carbazole-based boron dipyrromethene (BODIPY) dyes were synthesized by organometallic approaches. Thiazole, benzothiazole, imidazole, benzimidazole, triazole, and indolone substituents were introduced at the 1-position of the carbazole moiety, and boron complexation of each dipyrrin generated the corresponding compounds 1, 2 a, and 3-6. The properties of these products were investigated by UV/Vis and fluorescence spectroscopy, cyclic voltammetry, X-ray crystallography, and DFT calculations. These compounds exhibited large Stokes shifts, and compounds 1, 2 a, and 3-5 fluoresced both in solution and in the solid state. Complex 2 a showed the highest fluorescence quantum yield (ΦF) in the solid state, therefore boron complexes of the carbazole-benzothiazole hybrids 2 b-f, which had several different substituents, were prepared and the effects of the substituents on the photophysical properties of the compounds were examined. The fluorescence properties showed good correlation with the results of crystal-packing analyses, and the dyes exhibited color-tunable solid-state fluorescence.

    DOI: 10.1002/chem.201505150

    Scopus

    researchmap

  • Highly Active and Robust Metalloporphyrin Catalysts for the Synthesis of Cyclic Carbonates from a Broad Range of Epoxides and Carbon Dioxide

    Chihiro Maeda, Junta Shimonishi, Ray Miyazaki, Jun Ya Hasegawa, Tadashi Ema

    Chemistry - A European Journal   22 ( 19 )   6556 - 6563   2016年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bifunctional metalloporphyrins with quaternary ammonium bromides (nucleophiles) at the meta, para, or ortho positions of meso-phenyl groups were synthesized as catalysts for the formation of cyclic carbonates from epoxides and carbon dioxide under solvent-free conditions. The meta-substituted catalysts exhibited high catalytic performance, whereas the para- and ortho-substituted catalysts showed moderate and low activity, respectively. DFT calculations revealed the origin of the advantage of the meta-substituted catalyst, which could use the flexible quaternary ammonium cation at the meta position to stabilize various anionic species generated during catalysis. A zinc(II) porphyrin with eight nucleophiles at the meta positions showed very high catalytic activity (turnover number (TON)=240 000 at 120 °C, turnover frequency (TOF)=31 500h-1 at 170°C) at an initial CO2 pressure of 1.7MPa; catalyzed the reaction even at atmospheric CO2 pressure (balloon) at ambient temperature (20°C); and was applicable to a broad range of substrates, including terminal and internal epoxides. In a fix! Bifunctional metalloporphyrins act as catalysts for the formation of cyclic carbonates from epoxides and CO2 (see scheme). A comparison of the catalytic activities shows the superior performance of meta-substituted catalysts. A robust zinc(II) porphyrin with eight nucleophiles at the meta positions shows the highest catalytic activity and a broad substrate scope, including terminal and internal epoxides.

    DOI: 10.1002/chem.201600164

    Scopus

    researchmap

  • Determination of enantiomeric excess of carboxylates by fluorescent macrocyclic sensors

    Ali Akdeniz, Tsuyoshi Minami, Sagiri Watanabe, Maki Yokoyama, Tadashi Ema, Pavel Anzenbacher

    Chemical Science   7 ( 3 )   2016 - 2022   2016年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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%.

    DOI: 10.1039/c5sc04235f

    Scopus

    researchmap

  • Bifunctional catalysts for the CO<inf>2</inf> fixation: Structural optimization to maximize the synergetic effect

    Chihiro Maeda, Tadashi Ema

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   74 ( 8 )   814 - 823   2016年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    We developed various metalloporphyrins as bifunctional catalysts for the synthesis of cyclic carbonates from epoxides and CO2 under solvent-free conditions. The structures of the bifunctional catalysts were optimized step by step. As a result, a Zn porphyrin bearing eight nucleophiles at the meta positions showed a high turnover number (TON = 240,000) at 120°C at 1.7 MPa CO2 and catalyzed the reaction even at atmospheric CO2 pressure (balloon) at ambient temperature (20°C). Triporphyrin catalysts showed very high catalytic activity: TON = 220,000 and TOF = 46,000 h-1 for the Mg triporphyrin, and TON = 310,000 and TOF = 40,000 h-1 for the Zn triporphyrin. The high catalytic activity of these bifunctional catalysts was due to the cooperative action of Mg2+ or Zn2+ and Br- and a conformational change (induced-fit) of the quaternary ammonium cation.

    DOI: 10.5059/yukigoseikyokaishi.74.814

    Scopus

    researchmap

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

    Chihiro Maeda, Takumi Todaka, Tadashi Ema

    Organic Letters   17 ( 12 )   3090 - 3093   2015年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1021/acs.orglett.5b01363

    Scopus

    researchmap

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

    Tadashi Ema, Kazuki Fukuhara, Takashi Sakai, Masaki Ohbo, Fu Quan Bai, Jun Ya Hasegawa

    Catalysis Science and Technology   5 ( 4 )   2314 - 2321   2015年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1039/c5cy00020c

    Scopus

    researchmap

  • Bifunctional catalysts based on m-phenylene-bridged porphyrin dimer and trimer platforms: Synthesis of cyclic carbonates from carbon dioxide and epoxides

    Chihiro Maeda, Tomoya Taniguchi, Kanae Ogawa, Tadashi Ema

    Angewandte Chemie - International Edition   54 ( 1 )   134 - 138   2015年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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: 220000 and 46000 h-1, respectively, for the magnesium catalyst, and 310000 and 40000 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.

    DOI: 10.1002/anie.201409729

    Scopus

    researchmap

  • Chemical modification of lipase for rational enhancement of enantioselectivity

    Tadashi Ema, Hiroki Inoue

    Chemistry Letters   44 ( 10 )   1374 - 1376   2015年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chemical modifications of the I287C mutant of a Burkholderia cepacia lipase afforded various I287C-X conjugates, among which I287C-PAA bearing an N-phenylacetamide (PAA) moiety showed excellent enantioselectivity and catalytic activity for secondary alcohols. Site-directed chemical modifications are powerful tools to control enantioselective biocatalysis.

    DOI: 10.1246/cl.150667

    Scopus

    researchmap

  • Bifunctional porphyrin catalysts for the synthesis of cyclic carbonates from epoxides and CO <inf>2</inf> : Structural optimization and mechanistic study

    Tadashi Ema, Yuki Miyazaki, Junta Shimonishi, Chihiro Maeda, Jun Ya Hasegawa

    Journal of the American Chemical Society   136 ( 43 )   15270 - 15279   2014年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    We prepared bifunctional Mg II porphyrin catalysts 1 for the solvent-free synthesis of cyclic carbonates from epoxides and CO 2 . 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 Mg II 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 CO 2 pressures in the 1-6 MPa range, suggesting that CO 2 was not involved in the rate-determining step in this pressure range. No reaction proceeded in supercritical CO 2 , probably because the epoxide (into which the catalyst dissolved) dissolved in and was diluted by the supercritical CO 2 . Experiments with 18 O-labeled CO 2 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 CO 2 insertion to afford a CO 2 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 Mg II and Br - and a conformational change (induced-fit) of the quaternary ammonium cation.

    DOI: 10.1021/ja507665a

    Scopus

    researchmap

  • Selective anion sensing by chiral macrocyclic receptors with multiple hydrogen-bonding sites

    Tadashi Ema, Keiichi Okuda, Sagiri Watanabe, Takayuki Yamasaki, Tsuyoshi Minami, Nina A. Esipenko, Pavel Anzenbacher

    Organic Letters   16 ( 5 )   1302 - 1305   2014年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2014 American Chemical Society.

    DOI: 10.1021/ol403643d

    Scopus

    PubMed

    researchmap

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

    Tadashi Ema, Takuzo Komiyama, Satomi Sunami, Takashi Sakai

    RSC Advances   4 ( 5 )   2523 - 2525   2014年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2014 The Royal Society of Chemistry.

    DOI: 10.1039/c3ra45888a

    Scopus

    researchmap

  • Multifunctional macrocyclic receptors as templates for aromatic amino acids: A rare example of a highly selective multi-input multi-output chemo-"Logic Gate"

    Caterina Fraschetti, Antonello Filippi, Maria Elisa Crestoni, Tadashi Ema, Maurizio Speranza

    ChemPlusChem   78 ( 9 )   979 - 987   2013年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Proton-bound [M×H×G]+ diastereomeric complexes between some chiral aromatic amino acids or dipeptides(G) and a chiral multifunctional macrocyclic receptor (M=Chirabite-A) undergo, in the gas phase, highly selective substitution and addition reactions by amines, such as 2-aminobutane and piperidine. All the [M×H×G]+ complexes follow time-dependent monoexponential decays. In some cases, the kinetic curves exhibit a plateau revealing the presence of unreactive [M×H×G] + structures. In them, the amino acid is accommodated in the macrocycle cavity in the zwitterionic form by sharing its acidic hydrogen atoms with the pyridine nitrogen atoms of the host. The same interactions are structurally inaccessible to G=dipeptides or monofunctional amines, which then can be readily released from [M×H×G]+. When the amino acid interacts with the amidocarbonyl oxygen atoms pointing outside the macrocycle cavity, it saves the canonical structure and can be readily displaced by the amine. The Chirabite-A may act as an efficient template for aromatic amino acids by releasing them or not depending upon the amino acid configuration and the basicity of the amine. These unique properties confer to the gas-phase diastereomeric [M×H×G]+ complexes the features of multi-input multi-output chemo-"logic gates". © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    DOI: 10.1002/cplu.201300086

    Scopus

    researchmap

  • Robust porphyrin catalysts immobilized on biogenous iron oxide for the repetitive conversions of epoxides and CO<inf>2</inf> into cyclic carbonates

    Tadashi Ema, Yuki Miyazaki, Tomoya Taniguchi, Jun Takada

    Green Chemistry   15 ( 9 )   2485 - 2492   2013年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2013 The Royal Society of Chemistry.

    DOI: 10.1039/c3gc41055b

    Scopus

    researchmap

  • Unexpected behavior of diastereomeric ions in the GasPhase: A stimulus for pondering on ee measurements by ESI-MS

    Caterina Fraschetti, Antonello Filippi, Maria Elisa Crestoni, Tadashi Ema, Maurizio Speranza

    Journal of the American Society for Mass Spectrometry   24 ( 4 )   573 - 578   2013年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The most common protocols for the quantitative determination of the enantiomeric excess (ee) of raw mixtures by ESI-MS reveal inadequate in cases where the distribution of diastereomeric derivatives diverges from the ee of original solutions. This phenomenon is attributable to a matrix effect, i.e.; to the stereospecific formation of high order noncovalent adducts in the ESI droplets, which alters the actual availability of the diastereomeric species under MS analysis. In this frame, the assumption of classic protocols that the ionization correction factor q is independent on the composition of the mixture submitted to analysis is questionable. An alternative methodology is presented in this paper, which is aimed at circumventing the problem by excluding any chemical derivatization of the original raw mixture. It is based on the measurement of the actual distribution of ESI-formed proton-bound diastereomeric complexes from the enantiomeric mixture through a careful analysis of their reaction kinetics with a suitable reactant. [Figure not available: see fulltext.] © 2013 American Society for Mass Spectrometry.

    DOI: 10.1007/s13361-012-0575-8

    Scopus

    PubMed

    researchmap

  • Synthetic macrocyclic receptors in chiral analysis and separation

    Tadashi Ema

    Journal of Inclusion Phenomena and Macrocyclic Chemistry   74 ( 1-4 )   41 - 55   2012年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2012 Springer Science+Business Media B.V.

    DOI: 10.1007/s10847-012-0136-6

    Scopus

    researchmap

  • Construction of contiguous tetrasubstituted carbon stereocenters by intramolecular crossed benzoin reactions catalyzed by N-heterocyclic carbene (NHC) organocatalyst

    Tadashi Ema, Kumiko Akihara, Ryoko Obayashi, Takashi Sakai

    Advanced Synthesis and Catalysis   354 ( 17 )   3283 - 3290   2012年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    DOI: 10.1002/adsc.201200499

    Scopus

    researchmap

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

    Tadashi Ema, Yasuko Nakano, Daiki Yoshida, Shusuke Kamata, Takashi Sakai

    Organic and Biomolecular Chemistry   10 ( 31 )   6299 - 6308   2012年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © The Royal Society of Chemistry 2012.

    DOI: 10.1039/c2ob25614b

    Scopus

    PubMed

    researchmap

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

    Tadashi Ema, Yuki Miyazaki, Shohei Koyama, Yuya Yano, Takashi Sakai

    Chemical Communications   48 ( 37 )   4489 - 4491   2012年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    We have developed a very active bifunctional porphyrin catalyst showing a high turnover number (TON = 103 000) for the synthesis of cyclic carbonates from CO2 and epoxides under solvent-free conditions. © 2012 Royal Society of Chemistry.

    DOI: 10.1039/c2cc30591g

    Scopus

    researchmap

  • Biogenous iron oxide-immobilized palladium catalyst for the solvent-free Suzuki-Miyaura coupling reaction

    Kyoko Mandai, Toshinobu Korenaga, Tadashi Ema, Takashi Sakai, Mitsuaki Furutani, Hideki Hashimoto, Jun Takada

    Tetrahedron Letters   53 ( 3 )   329 - 332   2012年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Iron oxide produced by iron-oxidizing bacteria, Leptothrix ochracea, (biogenous iron oxide: BIO) was used as a support for immobilized palladium catalysts with organic cross-linkers. Palladium immobilized on BIO bearing imidazolium chloride delivered the desired biaryl products in sufficient yields in the Suzuki-Miyaura coupling reactions under solvent-free conditions and could be reused several times without significant loss of catalytic activity. It is shown that BIO can be exploited as a useful support for immobilization of palladium and the BIO-immobilized palladium catalyst effectively promotes the solvent-free Suzuki-Miyaura coupling reactions. © 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetlet.2011.11.044

    Scopus

    researchmap

  • Molecular recognition of chiral diporphyrin receptor with a macrocyclic cavity for intercalation of aromatic compounds

    Tadashi Ema, Norichika Ura, Katsuya Eguchi, Takashi Sakai

    Bulletin of the Chemical Society of Japan   85 ( 1 )   101 - 109   2012年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chiral diporphyrin receptor 1, which has a macrocyclic cavity for the intercalation of aromatic guest molecules, was designed and synthesized from pyrrole in five steps. The binding constants (Ka) revealed the greater affinity of 1 for more electron-deficient aromatic guests. The complexation between 1 and 1,3,5-trinitrobenzene (G8) (Ka = 1850M -1) was much stronger than that between porphyrin monomer 3 and G8 (Ka = 50M -1). This result strongly suggests that G8 was intercalated into the cavity of 1 via cooperative double π-π stacking. Interestingly, 1 enabled the naked-eye detection of an aromatic explosive G8; a dark-red solution of 1 in CHCl3 turned into a colloidal suspension upon addition of G8, and the light was scattered. Fluorescence spectroscopy was also useful for the selective detection of G8; fluorescence of 1 was quenched by complexation with G8, which was visible with the naked eye. Despite modest binding constants for dinitrobenzene derivatives, 1 showed a good ability to discriminate the enantiomers of twelve chiral compounds bearing a dinitrophenyl group by NMR spectroscopy. The MM calculations with the MM3 force field reproduced inclusion complexes between 1 and nitroaromatic compounds. The mechanism of chiral discrimination is proposed. © 2012 The Chemical Society of Japan.

    DOI: 10.1246/bcsj.20110230

    Scopus

    researchmap

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

    Tadashi Ema, Norichika Ura, Katsuya Eguchi, Yuhei Ise, Takashi Sakai

    Chemical Communications   47 ( 21 )   6090 - 6092   2011年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2011 The Royal Society of Chemistry.

    DOI: 10.1039/c1cc11572c

    Scopus

    PubMed

    researchmap

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

    Tadashi Ema, Yuki Miyazaki, Izumi Kozuki, Takashi Sakai, Hideki Hashimoto, Jun Takada

    Green Chemistry   13 ( 11 )   3187 - 3195   2011年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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 cepacia lipase (BCL) immobilized on BIO-M showed a turnover frequency of 33 000 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. © 2011 The Royal Society of Chemistry.

    DOI: 10.1039/c1gc15877e

    Scopus

    researchmap

  • Bifunctional organocatalyst for activation of carbon dioxide and epoxide to produce cyclic carbonate: Betaine as a new catalytic motif

    Yoshihiro Tsutsumi, Kyohei Yamakawa, Masahiko Yoshida, Tadashi Ema, Takashi Sakai

    Organic Letters   12 ( 24 )   5728 - 5731   2010年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bifunctional organocatalysts bearing an ammonium betaine framework have been developed as a new catalytic motif for the activation of carbon dioxide and epoxides to produce cyclic carbonates. © 2010 American Chemical Society.

    DOI: 10.1021/ol102539x

    Scopus

    researchmap

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

    Tadashi Ema, Taro Kadoya, Kumiko Akihara, Takashi Sakai

    Journal of Molecular Catalysis B: Enzymatic   66 ( 1-2 )   198 - 202   2010年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2010 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.molcatb.2010.05.009

    Scopus

    researchmap

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

    Tadashi Ema, Shusuke Kamata, Masahiro Takeda, Yasuko Nakano, Takashi Sakai

    Chemical Communications   46 ( 30 )   5440 - 5442   2010年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © The Royal Society of Chemistry 2010.

    DOI: 10.1039/c001561j

    Scopus

    PubMed

    researchmap

  • Synthesis and evaluation of chiral selectors with multiple hydrogen-bonding sites in the macrocyclic cavities

    Tadashi Ema, Kazuki Hamada, Kyoko Sugita, Yohei Nagata, Takashi Sakai, Atsushi Ohnishi

    Journal of Organic Chemistry   75 ( 13 )   4492 - 4500   2010年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (Figure presented) Chiral macrocycles with the hydrogen bond donor/acceptor sites in the cavity were synthesized and covalently bonded to silica gel to give chiral stationary phases (CSPs), which showed excellent abilities to resolve various chiral compounds including ketones, esters, carboxylic acids, sulfoxides, amines, amino acid derivatives, and metal complexes. The effect of the linker connecting the macrocyclic moiety to silica was examined, and a more electronegative substituent was found to be better. Various organic solvents could be used as the mobile phase to optimize the resolution efficiency of the CSPs. Although the separation factors (α) tended to decrease with an increase in the solvent polarity, remarkable solvent tolerance was also observed. In some cases, even MeCN and MeOH could be used for the complete resolution of enantiomers. The MM calculations suggested that the chiral recognition of Co(acac)3 is achieved by a combination of steric interactions and hydrogen bonds between the carbonyl O atom coordinated to the Co atom and the macrocyclic amide NH groups. The attachment of substituents to the 3,3′-positions of the binaphthyl moiety improved chiral HPLC performance in some cases. In particular, CSP-1d, having the Br atoms, showed the best performance for several analytes. © 2010 American Chemical Society.

    DOI: 10.1021/jo1006587

    Scopus

    researchmap

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

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

    Organic and Biomolecular Chemistry   8 ( 2 )   336 - 338   2010年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2010 The Royal Society of Chemistry.

    DOI: 10.1039/b919497e

    Scopus

    PubMed

    researchmap

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

    Tadashi Ema, Norichika Ura, Masataka Yoshii, Toshinobu Korenaga, Takashi Sakai

    Tetrahedron   65 ( 46 )   9583 - 9591   2009年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    We derived a novel equation capable of predicting the degree of enantioselectivity in a catalytic reaction without any knowledge of the reaction mechanism and/or the transition-state structure, and tested the validity of this equation by changing substrates systematically in the lipase or oxazaborolidine-catalyzed reactions. A good correlation was observed between the predicted and observed E values, and the stereochemistry of the products could be predicted correctly in most cases (28 out of 30). © 2009 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2009.09.058

    Scopus

    researchmap

  • Stereoselective synthesis of bicyclic tertiary alcohols with quaternary stereocenters via intramolecular crossed benzoin reactions catalyzed by n-heterocyclic carbenes

    Tadashi Ema, Yoshitaka Oue, Kumiko Akihara, Yuki Miyazaki, Takashi Sakai

    Organic Letters   11 ( 21 )   4866 - 4869   2009年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2009 American Chemical Society.

    DOI: 10.1021/ol9019293

    Scopus

    researchmap

  • Tuning the chiral cavity of macrocyclic receptor for chiral recognition and discrimination

    Tadashi Ema, Daisuke Tanida, Kazuki Hamada, Takashi Sakai

    Journal of Organic Chemistry   73 ( 22 )   9129 - 9132   2008年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (Chemical Equation Presented) The size and shape of the chiral cavity of a macrocyclic receptor were tuned by the alteration of the binaphthyl moiety to improve the chiral recognition/discrimination ability. For example, host 3 with the 3,5-bis(trifluoromethyl)phenyl group at the 3,3′-positions showed improved enantioselectivity for small molecules such as 2-chloropropionic acid and methyl lactate as evaluated by the binding constants. This host 3 also had an excellent ability as an NMR chiral solvating agent. © 2008 American Chemical Society.

    DOI: 10.1021/jo801584b

    Scopus

    PubMed

    researchmap

  • Highly efficient chemoenzymatic synthesis of methyl (R)-o-chloromandelate, a key intermediate for clopidogrel, via asymmetric reduction with recombinant Escherichia coli

    Tadashi Ema, Sayaka Ide, Nobuyasu Okita, Takashi Sakai

    Advanced Synthesis and Catalysis   350 ( 13 )   2039 - 2044   2008年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

    DOI: 10.1002/adsc.200800292

    Scopus

    researchmap

  • Lipase-catalyzed dynamic kinetic resolution giving optically active cyanohydrins: use of silica-supported ammonium hydroxide and porous ceramic-immobilized lipase

    Takashi Sakai, Kefei Wang, Tadashi Ema

    Tetrahedron   64 ( 9 )   2178 - 2183   2008年2月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Synthetically useful cyanohydrin acetates, ArCH(OAc)CN (Ar=C6H5, 3,4-methylenedioxyphenyl, 4-Me-C6H4, 4-Cl-C6H4, 4-F-C6H4, 4-CF3-C6H4), were successfully synthesized in high enantiomeric purities (79-93% ee) via the lipase-catalyzed dynamic kinetic resolution (DKR) of cyanohydrins synthesized in situ from the corresponding aldehydes and acetone cyanohydrin. The combined use of silica-supported BTAH (benzyltrimethylammonium hydroxide) and porous ceramic-immobilized lipase under the optimized reaction conditions enabled the remarkable acceleration of the enantioselective DKR reactions. © 2007 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2007.12.030

    Scopus

    researchmap

  • Hydrolase-catalyzed kinetic resolution of 5-[4-(1-hydroxyethyl)phenyl]-10, 15,20-tris(pentafluorophenyl)porphyrin in ionic liquids

    Tadashi Ema, Tokuhiro Doi, Takashi Sakai

    Chemistry Letters   37 ( 1 )   90 - 91   2008年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bulky alcohol, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-tris- (pentafluorophenyl)porphyrin (1b), was synthesized, and enantiomerically pure alcohol 1b and ester 2b were obtained by a single kinetic resolution catalyzed by Candida antarctica lipase in i-Pr2O and in [bdmim] [PF 6]. Copyright © 2008 The Chemical Society of Japan.

    DOI: 10.1246/cl.2008.90

    Scopus

    researchmap

  • Highly active and robust organic-inorganic hybrid catalyst for the synthesis of cyclic carbonates from carbon dioxide and epoxides

    Takashi Sakai, Yoshihiro Tsutsumi, Tadashi Ema

    Green Chemistry   10 ( 3 )   345 - 349   2008年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A high-throughput combinatorial strategy enabled us to find a highly active organic-inorganic hybrid catalyst for the production of cyclic carbonates from CO2 and epoxides. The best hybrid catalyst 1a was prepared by the coupling of 3-(triethoxysilyl)propyltriphenylphosphonium bromide and mesoporous silica, and the organic and inorganic moieties had a synergistic effect on catalytic activity. The pore size of silica was found to be important for catalysis; mesoporous silica with the mean pore size of 19 nm exhibited much better performance than silica with that of 6 nm. The solvent-free and metal-free reactions proceeded successfully under very mild conditions (1 MPa, 90 °C, 1 mol% loading of catalyst, 6 h), and the hybrid catalyst could be recycled ten times. © The Royal Society of Chemistry.

    DOI: 10.1039/b718321f

    Scopus

    researchmap

  • Chiral selector with multiple hydrogen-bonding sites in a macrocyclic cavity

    Tadashi Ema, Daisuke Tanida, Kyoko Sugita, Takashi Sakai, Ken Ichiro Miyazawa, Atsushi Ohnishi

    Organic Letters   10 ( 12 )   2365 - 2368   2008年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (Chemical Equation Presented) Chiral macrocycles with the hydrogen bond donor/acceptor sites in the cavity were synthesized and covalently bonded to silica gel to give chiral stationary phases (CSPs), which showed excellent abilities to resolve various chiral compounds, such as benzoin and Co(acac) 3, in HPLC. Various organic solvents could be used as the mobile phase to optimize the resolution efficiency of CSPs, and in some cases, even MeCN, MeOH, and CO2 could be used for the complete resolution of enantiomers. © 2008 American Chemical Society.

    DOI: 10.1021/ol800940j

    Scopus

    PubMed

    researchmap

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

    Tadashi Ema, Daisuke Tanida, Tatsuya Matsukawa, Takashi Sakai

    Chemical Communications   ( 8 )   957 - 959   2008年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © The Royal Society of Chemistry.

    DOI: 10.1039/b718763g

    Scopus

    PubMed

    researchmap

  • Versatile and practical macrocyclic reagent with multiple hydrogen-bonding sites for chiral discrimination in NMR

    Tadashi Ema, Daisuke Tanida, Takashi Sakai

    Journal of the American Chemical Society   129 ( 34 )   10591 - 10596   2007年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bifunctional macrocycles 1-4 and diamide 5 were designed and synthesized. NMR studies demonstrated that, among them, receptor 1 functions as the best chiral solvating agent (shift reagent), which is effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, carbonate, lactone, alcohol, sulfoxide, sulfoximine, sulfinamide, isocyanate, or epoxide functionality. The addition of only 5 mol % (69 μg, 0.15 mM) of 1 splits the enantiomeric signals of sulfoxide 13. The excellent performance of 1 as a chiral solvating agent, such as versatility, signal sharpness, high splitting ability, high sensitivity, wide detection window, and synthetic accessibility, is reported. NMR studies revealed that the principal binding site of 1 is the two amide NH groups of the lower segment and that the additional binding site is the pyridyl nitrogen. The V-shaped arrangement of the two 2,6-diacylaminopyridine moieties as constructed in 1 was found to be much more effective for binding a variety of compounds than the parallel alignment of the two binding motifs as constructed in 4. The NO2 group in 1 enhanced not only the binding ability but also the degree of enantioselectivity. Unexpectedly, the comparisons between 1 and 3 enabled us to find the importance of the relative orientation of the binaphthyl moiety; the orthogonal disposition of the binaphthyl moiety in 1 most effectively brings about the differential ring-current effect on the chiral guest molecule bound, which leads to the high degree of chiral discrimination in NMR. © 2007 American Chemical Society.

    DOI: 10.1021/ja073476s

    Scopus

    researchmap

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

    Tadashi Ema, Nobuyasu Okita, Sayaka Ide, Takashi Sakai

    Organic and Biomolecular Chemistry   5 ( 8 )   1175 - 1176   2007年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © The Royal Society of Chemistry.

    DOI: 10.1039/b703463f

    Scopus

    PubMed

    researchmap

  • Versatile and practical chiral shift reagent with hydrogen-bond donor/acceptor sites in a macrocyclic cavity

    Tadashi Ema, Daisuke Tanida, Takashi Sakai

    Organic Letters   8 ( 17 )   3773 - 3775   2006年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bifunctional macrocycle 1 with C2 symmetry was newly synthesized. NMR studies demonstrated that receptor 1 functions as a chiral shift reagent (solvating agent) that is highly effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, lactone, alcohol, sulfoxide, sulfoximine, isocyanate, or epoxide functionality. Binding constants were determined to investigate the binding behavior of 1. © 2006 American Chemical Society.

    DOI: 10.1021/ol0613665

    Scopus

    researchmap

  • Asymmetric reduction of ketones using recombinant E. coli cells that produce a versatile carbonyl reductase with high enantioselectivity and broad substrate specificity

    Tadashi Ema, Hideo Yagasaki, Nobuyasu Okita, Masahiro Takeda, Takashi Sakai

    Tetrahedron   62 ( 26 )   6143 - 6149   2006年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The gene encoding a versatile biocatalyst that shows high enantioselectivity for a variety of ketones, SCR (Saccharomyces cerevisiae carbonyl reductase), has been identified, cloned, and expressed in Escherichia coli. Two types of expression systems with high NADPH-regenerating capacities have been constructed. One is the tandem system, where the genes encoding SCR and GDH (glucose dehydrogenase) are located in the same plasmid, and the other is the two-plasmid system, where each of the SCR and GDH genes is located in separate plasmids that can coexist in one E. coli cell. Asymmetric reduction of ketones with the recombinant E. coli cells gave synthetically useful 20 alcohols, 11 of which were enantiomerically pure. The productivity of one of these products was as high as 41 g/L. © 2006 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2006.04.061

    Scopus

    researchmap

  • Synthesis of molecular tweezers bearing pentafluorophenyl and several pendant aryl groups. Effective application of the modified Suzuki-Miyaura coupling reaction

    Toshinobu Korenaga, Takahiro Kosaki, Yusuke Kawauchi, Tadashi Ema, Takashi Sakai

    Journal of Fluorine Chemistry   127 ( 4-5 SPEC. ISS. )   604 - 609   2006年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A molecular tweezer bearing two pentafluorophenyl groups 2b and its o-methylated aryl homologue 2c were newly synthesized by the slight modification of the known procedure. The low yield in the introduction of pentafluorophenyl group to the precursor dibromide 6 was improved by application of the modified Suzuki-Miyaura coupling reaction using C6F5B(OH)2 with Pd2(dba)3/P(t-Bu)3/CsF/Ag2O catalytic system, which was recently developed by us. © 2006 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jfluchem.2005.12.007

    Scopus

    researchmap

  • Suzuki-Miyaura coupling reaction using pentafluorophenylboronic acid

    Toshinobu Korenaga, Takahiro Kosaki, Rokki Fukumura, Tadashi Ema, Takashi Sakai

    Organic Letters   7 ( 22 )   4915 - 4917   2005年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (Chemical Equation Presented) We have found new conditions for the Suzuki-Miyaura coupling reaction applicable to pentafluorophenylboronic acid (C6F5B(OH)2) (1), which is an inactive substrate under normal conditions. The reactions of 1 with phenyl iodide or bromide under Pd(PPh3)4/CsF/Ag2O or Pd 2(dba)3/ P(t-Bu)3/CsF/Ag2O catalytic system conditions gave 2,3,4,5,6-pentafluoro-1,1′-biphenyl (3a) in more than 90% yields. Combination of CsF and Ag2O was essential for promoting these reactions. © 2005 American Chemical Society.

    DOI: 10.1021/ol051866i

    Scopus

    researchmap

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

    Tadashi Ema, Toshiyuki Fujii, Misa Ozaki, Toshinobu Korenaga, Takashi Sakai

    Chemical Communications   ( 37 )   4650 - 4651   2005年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © The Royal Society of Chemistry 2005.

    DOI: 10.1039/b508244g

    Scopus

    PubMed

    researchmap

  • Highly sensitive chiral shift reagent bearing two zinc porphyrins

    Tadashi Ema, Nozomi Ouchi, Tokuhiro Doi, Toshinobu Korenaga, Takashi Sakai

    Organic Letters   7 ( 18 )   3985 - 3988   2005年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (Chemical Equation Presented) A new type of chiral receptor (R,R)- or (S,S)-1b with C2 symmetry was synthesized. An induced-fit type of binding behavior of 1b for diamines was revealed by CD spectroscopy. NMR studies demonstrated that 1b can function as a highly sensitive chiral shift reagent for the determination of the enantiomeric purity of chiral diamines, aziridine, and isoxazoline at the microgram level. © 2005 American Chemical Society.

    DOI: 10.1021/ol0514808

    Scopus

    researchmap

  • Kinetic resolution of 5-(hydroxymethyl)-3-phenyl-2-isoxazoline by using the 'low-temperature method' with porous ceramic-immobilized lipase

    Takashi Sakai, Hiroshi Mitsutomi, Toshinobu Korenaga, Tadashi Ema

    Tetrahedron Asymmetry   16 ( 8 )   1535 - 1539   2005年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A significant enhancement of the enantioselectivity (E value = 249) in the lipase-catalyzed resolution of a primary alcohol, racemic 5-(hydroxymethyl)-3- phenyl-2-isoxazoline (±)-1, was obtained by using the 'low-temperature method' (-60°C) with porous ceramic-immobilized lipase (Amano PS-C II) and vinyl acetate in acetone. © 2005 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetasy.2005.02.025

    Scopus

    researchmap

  • Asymmetric reduction of a variety of ketones with a recombinant carbonyl reductase: Identification of the gene encoding a versatile biocatalyst

    Tadashi Ema, Hideo Yagasaki, Nobuyasu Okita, Kumiko Nishikawa, Toshinobu Korenaga, Takashi Sakai

    Tetrahedron Asymmetry   16 ( 6 )   1075 - 1078   2005年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The gene encoding a versatile biocatalyst that shows high enantioselectivity for a variety of ketones, SCR (Saccharomyces cerevisiae carbonyl reductase), has been identified, cloned, and expressed in E. coli. Recombinant E. coli co-producing SCR and GDH (glucose dehydrogenase) is an easy-to-use, synthetically useful biocatalyst, and 8 out of the 16 alcohols obtained had enantiomeric purities of >98% ee. © 2005 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetasy.2005.02.004

    Scopus

    researchmap

  • Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers

    Takashi Sakai, Yu Liu, Hiroshi Ohta, Toshinobu Korenaga, Tadashi Ema

    Journal of Organic Chemistry   70 ( 4 )   1369 - 1375   2005年2月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    (Chemical Equation Presented) Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (±)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 °C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (±)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 °C). Compound (±)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (±)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13.

    DOI: 10.1021/jo048243n

    Scopus

    PubMed

    researchmap

  • Synthesis of a molecular tweezer containing pentafluorophenyl groups and investigation of the π-π stacking interaction for a pentafluorophenyl group in a polar organic solvent

    Toshinobu Korenaga, Yusuke Kawauchi, Takahiro Kosaki, Tadashi Ema, Takashi Sakai

    Bulletin of the Chemical Society of Japan   78 ( 12 )   2175 - 2179   2005年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A molecular tweezer having two bidentate pentafluorophenyl (C 6F 5) groups was synthesized, and the π-π stacking ability of the C 6F 5 groups toward benzene derivatives in a polar organic solvent was evaluated. The structure of the molecular tweezer was revealed to be dimeric in the crystalline state by X-ray analysis. Association constants (K a) between the molecular tweezer and aromatic guests in THF were found to be roughly correlated with the quadrupole moment (Q zz) of the guests, suggesting that the quadrupole-quadrupole contribution plays a significant role in the π-π interaction even in a polar organic solvent. © 2005 The Chemical Society of Japan.

    DOI: 10.1246/bcsj.78.2175

    Scopus

    researchmap

  • Reestimation of the Taft's substituent constant of the pentafluorophenyl group

    Toshinobu Korenaga, Koichi Kadowaki, Tadashi Ema, Takashi Sakai

    Journal of Organic Chemistry   69 ( 21 )   7340 - 7343   2004年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The Taft's substituent constant of the pentafluorophenyl group (σ*C6F5)) was reestimated to be 1.50 by correlation between IR spectral data (vC=O) and σ* constants for a series of esters (involving the pentafluorobenzyl group) of 3-phenylpropanoic acid and butanoic acid. The possibility of the disturbance of the correlation by the intramolecular π-π interaction between C 6F5 and C6H5 groups in pentafluorobenzyl 3-phenylpropanoate was excluded by ab initio and DFT calculations of the stable conformations and their carbonyl frequencies. The reestimated σ* (C6F5) value was used for calculation of the pKa value of pentafluorobenzyl alcohol [14.5 (or 14.3)].

    DOI: 10.1021/jo048939g

    Scopus

    researchmap

  • The effect of temperature on the lipase-catalyzed asymmetric protonation of 1-acetoxy-2-methylcyclohexene giving (R)-2-methylcyclohexanone

    Takashi Sakai, Akiko Matsuda, Yuko Tanaka, Toshinobu Korenaga, Tadashi Ema

    Tetrahedron Asymmetry   15 ( 12 )   1929 - 1932   2004年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Lipase-catalyzed enantioface-selective protonation of the enol acetate of 2-methylcyclohexanone was performed by using Burkholderia cepacia lipase immobilized on porous ceramic particles, 'Lipase PS-C II' (Amano Enzyme Inc.), in i-Pr2O and ethanol, giving (R)-2-methylcyclohexanone with 77% ee at best with 82% conversion at 0°C. The enantioselectivity (E-value) was found to be temperature dependent and significant in controlling the efficiency of the asymmetric protonation. © 2004 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetasy.2004.05.008

    Scopus

    researchmap

  • Synthesis of enantiomerically pure (R,R)- and (S,S)-1,2-Bis(pentafluorophenyl)ethane-1,2-diamine and evaluation of the pK <inf>a</inf> value by ab initio calculations

    Takashi Sakai, Toshinobu Korenaga, Noriyuki Washio, Yuji Nishio, Shinichi Minami, Tadashi Ema

    Bulletin of the Chemical Society of Japan   77 ( 5 )   1001 - 1008   2004年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    1,2-Bis(pentafluorophenyl)ethane-1,2-diamine (1) was synthesized by the imino pinacol coupling of 4-methoxy-N-(pentafluorobenzylidene)benzylamine using a Zn-Cu couple and p-TsOH·H2O. The optical resolution of (±)-1 by means of chiral HPLC gave enantiomerically pure (R,R)- and (S,S)-1. The pKa value of 1 was estimated by a titration experiment and ab initio calculations, showing that 1 has a basicity comparable to aniline derivatives.

    DOI: 10.1246/bcsj.77.1001

    Scopus

    researchmap

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

    Tadashi Ema, Masafumi Kageyama, Toshinobu Korenaga, Takashi Sakai

    Tetrahedron Asymmetry   14 ( 24 )   3943 - 3947   2003年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2003 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetasy.2003.09.040

    Scopus

    researchmap

  • Intermolecular oxygen atom⋯π interaction in the crystal packing of chiral amino alcohol bearing a pentafluorophenyl group

    Toshinobu Korenaga, Hikaru Tanaka, Tadashi Ema, Takashi Sakai

    Journal of Fluorine Chemistry   122 ( 2 )   201 - 205   2003年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Presence of an unique atom-to-face alcoholic oxygen atom⋯π interaction between a pentafluorophenyl group and alcoholic oxygen (O⋯π) has been demonstrated by X-ray analysis of the novel chiral amino alcohol instead of the well-known interaction between usual aromatic ring and alcoholic hydrogen atom (OH⋯π). © 2003 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0022-1139(03)00089-7

    Scopus

    researchmap

  • Enhancement of the efficiency of the low temperature method for kinetic resolution of primary alcohols by optimizing the organic bridges in porous ceramic-immobilized lipase

    Takashi Sakai, Kyoko Hayashi, Fumika Yano, Mie Takami, Megumi Ino, Toshinobu Korenaga, Tadashi Ema

    Bulletin of the Chemical Society of Japan   76 ( 7 )   1441 - 1446   2003年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    For the enhancement of enantioselectivity and acceleration of the reaction rate in the lipase-catalyzed resolution of primary alcohols, the use of a very low reaction temperature (-30 °C) and an immobilized lipase on organic bridges-coated porous ceramic support was found to be highly effective. Furthermore, the structure of the organic bridges greatly influenced the temperature effect between in E and 1/T as well as the reaction rate. Among the organic bridges examined in the resolution of (±)-2-hydroxymethyl-1,4-benzodioxane, the 6-(2-methylpropanoyloxy)hexylsilanetrioxyl bridge was the best choice for both the E value and the reaction rate at -30 °C.

    DOI: 10.1246/bcsj.76.1441

    Scopus

    researchmap

  • Transition-state models are useful for versatile biocatalysts: Kinetics and thermodynamics of enantioselective acylations of secondary alcohols catalyzed by lipase and subtilisin

    Tadashi Ema, Kunihiro Yamaguchi, Yuji Wakasa, Akinori Yabe, Ryoichi Okada, Minoru Fukumoto, Fumika Yano, Toshinobu Korenaga, Masanori Utaka, Takashi Sakai

    Journal of Molecular Catalysis B: Enzymatic   22 ( 3-4 )   181 - 192   2003年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Lipases and subtilisins are versatile enzymes capable of showing high enantioselectivity and broad substrate specificity simultaneously. The transition-state models previously proposed to rationalize this important feature were intensively examined from kinetic and thermodynamic viewpoints. Kinetic measurements reaffirmed that chiral discrimination originates from the transition state and that the enantioselectivity results from the reduced activity of the enzymes for the slower-reacting enantiomer, but not from the enhanced activity for the faster-reacting enantiomer relative to a reference alcohol, cyclopentanol. The larger substituent of the slower-reacting enantiomers interacts repulsively with the protein in the transition state, and even the larger substituent of the faster-reacting enantiomers interacts unfavorably to some degree with the protein. A number of thermodynamic parameters, ΔΔH‡ and ΔΔS‡, for the subtilisin-catalyzed acylations of secondary alcohols were determined. A linear compensation effect was found between the ΔΔH‡ and ΔΔS‡ values. As the ΔΔH‡ value becomes negatively large, the ΔΔS‡ value also becomes negatively large. This observation is explained in terms of the transition-state model. Because the widely accepted concepts such as the lock-and-key mechanism and the induced-fit mechanism cannot account for the peculiar behavior of these enzymes toward unnatural substrates, a new category, the non-lock-and-key mechanism, has been proposed. © 2003 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S1381-1177(03)00034-1

    Scopus

    researchmap

  • Practical resolution of 3-phenyl-2H-azirine-2-methanol at very low temperature by using lipase immobilized on porous ceramic and optimized acylating agent

    Takashi Sakai, Akiko Matsuda, Toshinobu Korenaga, Tadashi Ema

    Bulletin of the Chemical Society of Japan   76 ( 9 )   1819 - 1821   2003年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A synthetically useful primary alcohol, 3-phenyl-2H-azirine-2-methanol, was resolved efficiently by a reaction at -40 °C with a lipase immobilized on the porous ceramic (Toyonite) and vinyl butanoate in ether (E value of 130 and TTN/h value of 7800).

    DOI: 10.1246/bcsj.76.1819

    Scopus

    researchmap

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

    Tadashi Ema, Masataka Yoshii, Toshinobu Korenaga, Takashi Sakai

    Tetrahedron Asymmetry   13 ( 11 )   1223 - 1229   2002年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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. © 2002 Elsevier Science Ltd. All rights reserved.

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

    Scopus

    researchmap

  • 5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin as a probe of the transition-state conformation in hydrolase-catalyzed enantioselective transesterifications

    Tadashi Ema, Masahito Jittani, Kenji Furuie, Masanori Utaka, Takashi Sakai

    Journal of Organic Chemistry   67 ( 7 )   2144 - 2151   2002年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin (1a) and zinc porphyrin 1b were designed and synthesized to experimentally examine the validity of the transition-state model previously proposed for the lipase-catalyzed kinetic resolution of secondary alcohols. The lipases from Pseudomonas cepacia (lipase PS), Candida antarctica (CHIRAZYME L-2), Rhizomucor miehei (CHIRAZYME L-9), and Pseudomonas aeruginosa (lipase LIP) exhibited excellent enantioselectivity (E > 100 at 30 °C). Subtilisin Carlsberg from Bacillus licheniformis (ChiroCLEC-BL) also showed high enantioselectivity for 1a (E = 140 at 30 °C), and the thermodynamic parameters were determined: ΔΔH‡ = -6.8 ± 0.8 kcal mol-1, ΔΔS‡ = -13 ± 3 cal mol-1 K-1. Lipases and subtilisin showed R- and S-preference for 1, respectively. The mechanisms underlying the experimental observations are explained in terms of the transition-state models. The large secondary alcohol 1 is a powerful tool for investigating the conformation of the transition state of the enzyme-catalyzed reactions. The fact that 1 was resolved with high enantioselectivity strongly suggests that the gauche conformation, but not the anti conformation, is taken in the transition state, in agreement with the transition-state models involving the stereoelectronic effect.

    DOI: 10.1021/jo0109063

    Scopus

    PubMed

    researchmap

  • High enantioselectivity and broad substrate specificity of a carbonyl reductase: Toward a versatile biocatalyst

    T. Ema, H. Moriya, T. Kofukuda, T. Ishida, K. Maehara, M. Utaka, T. Sakai

    Journal of Organic Chemistry   66 ( 25 )   8682 - 8684   2001年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/jo0108257

    Scopus

    PubMed

    researchmap

  • Hydrolase-catalyzed kinetic resolutions of chiral alcohols: Mechanistic study on the origin of the enantioselectivity

    Tadashi Ema, Takashi Sakai

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   58 ( 7 )   691 - 698   2000年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Mechanistic studies on the enantioselectivity in the hydrolase-catalyzed kinetic resolutions of racemic alcohols are described. Based on kinetic measurements, molecular orbital calculations and computer modeling with X-ray crystal structures of several lipases, we proposed the transition-state model that is consistent with the experimental observations such as (i) high enantioselectivity, (ii) broad substrate specificity and (iii) an empirical rule (R-preference for secondary alcohols). A large secondary alcohol having a tetraphenylporphyrin as the substituent was successfully resolved by several lipases, demonstrating the validity of our transition-state model. The S-preference of subtilisins for secondary alcohols was rationalized by applying the protocol used in the transition-state model for lipases to subtilisins. We also found that the lipase-catalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, the E value increased with decreasing temperature, and a linear relationship was observed between 1n E and 1/T, from which the ΔΔH‡ and ΔΔS‡ values were calculated. These thermodynamic parameters were useful for investigating the mechanism of the enantioselectivity of the hydrolases toward chiral alcohols.

    DOI: 10.5059/yukigoseikyokaishi.58.691

    Scopus

    researchmap

  • Lipase-catalyzed transesterification of 2-hydroxy-2- (pentafluorophenyl)acetonitrile leading to (1R,2R)-and (1S,2S)-bis (pentafluorophenyl)ethane-1,2-diol

    Takashi Sakai, Yasushi Miki, Masashi Tsuboi, Hiroaki Takeuchi, Tadashi Ema, Kenji Uneyama, Masanori Utaka

    Journal of Organic Chemistry   65 ( 9 )   2740 - 2747   2000年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Optically pure (IR,2R)- and (1S,2S)-1,2-bis(pentafluorophenyl)ethane- 1,2-diol (1) were synthesized from key intermediates (R)- and (S)-2-hydroxy- 2-(pentafluorophenyl)acetonitrile (2), both of which were prepared by the lipase LIP-catalyzed transesterification (E - 465). The absolute configuration of (S)-2 was determined by X-ray structural analysis after transformation into (S)-a-cyano-2,3,4,5,6-pentafluorobenzyl (S)-6-methoxy-a- methyl-2-naphthaleneacetate (S,S)-9. In addition, the crystal structure of (S,S)-9 has an interesting well-ordered packing pattern which shows face-to- face stacking interactions and end-to-end parallel contacts between the pentafluorophenyl and 6-methoxynaphthyl groups of the adjacent molecules.

    DOI: 10.1021/jo9918551

    Scopus

    researchmap

  • Compensation effect between differential activation enthalpy and entropy in subtilisin-catalyzed kinetic resolutions of secondary alcohols

    Tadashi Ema, Kunihiro Yamaguchi, Yuji Wakasa, Nobuaki Tanaka, Masanori Utaka, Takashi Sakai

    Chemistry Letters   ( 7 )   782 - 783   2000年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    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.

    DOI: 10.1246/cl.2000.782

    Scopus

    researchmap

  • Transition-state model for subtilisin-catalyzed transesterifications of secondary alcohols

    Ema Tadashi, Ryoichi Okada, Minoru Fukumoto, Masahito Jittani, Mikiko Ishida, Kenji Furuie, Kunihiro Yamaguchi, Takashi Sakai, Masanori Utaka

    Tetrahedron Letters   40 ( 23 )   4367 - 4370   1999年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    In the subtilisin-catalyzed transesterications of a variety of secondary alcohols, the (S)-enantiomers were acylated faster. Kinetic measurements indicated that the enantioselectivily originates from chiral discrimination in the transition state. A transition-state model capable of explaining the S-preference of subtilisin toward secondary alcohols has been proposed.

    DOI: 10.1016/S0040-4039(99)00750-9

    Scopus

    researchmap

  • Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols

    Takashi Sakai, Tetsuo Kishimoto, Yukie Tanaka, Tadashi Ema, Masanori Utaka

    Tetrahedron Letters   39 ( 43 )   7881 - 7884   1998年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Low-temperature method (-40 °C at best) for enhancement of the enantioselectivity in a lipase-catalyzed transesterification was proved to be widely applicable to primary and secondary alcohols and enabled theoretical prediction of the course of enhancement of the enantioselectivity physicochemically.

    DOI: 10.1016/S0040-4039(98)01747-X

    Scopus

    researchmap

  • Lipase-catalyzed kinetic resolution of large secondary alcohols having tetraphenylporphyrin

    Tadashi Ema, Masahito Jittani, Takashi Sakai, Masanori Utaka

    Tetrahedron Letters   39 ( 35 )   6311 - 6314   1998年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Large secondary alcohols, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20- triphenylporphyrin (1a) and the zinc complex 1b, designed on the basis of the transition-state model recently proposed by us, were subjected to the lipase- catalyzed transesterifications. The alcohols were resolved using lipases from Pseudomonas cepacia (lipase PS), Candida antarctica (CHIRAZYME L-2), Rhizomucor miehei (CHIRAZYME L-9), and Pseudomonas aeruginosa (lipase LIP) with high enantioselectivities (E > 100).

    DOI: 10.1016/S0040-4039(98)01338-0

    Scopus

    researchmap

  • Control of enantioselectivity in the baker's yeast asymmetric reduction of γ-chloro β-diketones to γ-chloro (S)-β-hydroxy ketones

    Jing Nan Cui, Tadashi Ema, Takashi Sakai, Masanori Utaka

    Tetrahedron Asymmetry   9 ( 15 )   2681 - 2692   1998年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    1-Chloro-2,4-alkanediones 1a-f prepared in one step were reduced using baker's yeast to afford 1-chloro-2-hydroxy-4-alkanones 2a-f regioselectively in S 29% to R 58% ee. Use of a small amount of organic solvents to dissolve the substrate enhanced the enantiomeric excess in favor of the S configuration. The function of the organic solvents was studied with reducing enzymes isolated from baker's yeast. Some polar solvents selectively inhibited the enzymes, while nonpolar solvents enhanced the concentration of substrate in water. Application of inhibitors with heat-treatment and organic solvents as additives enhanced the enantiomeric excesses of the products to S 66-96% ee.

    DOI: 10.1016/S0957-4166(98)00269-9

    Scopus

    researchmap

  • Highly Enantioselective Reduction of Carbonyl Compounds Using a Reductase Purified from Bakers' Yeast

    Tadashi Ema, Yasushi Sugiyama, Minoru Fukumoto, Hiroyuki Moriya, Jing Nan Cui, Takashi Sakai, Masanori Utaka

    Journal of Organic Chemistry   63 ( 15 )   4996 - 5000   1998年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    An NADPH-dependent reductase that shows reducing activity for 1-chloro-2-hexanone has been purified from bakers' yeast. SDS-PAGE and gel filtration suggested that the purified reductase is a monomeric enzyme with a molecular weight of ca. 37 kDa. Asymmetric reduction of several carbonyl compounds using the purified reductase has been carried out. 1-Chloro-2-hexanone, 1-acetoxy-2-heptanone, methyl acetoacetate, ethyl pyruvate, 1-chloro-2,4-pentanedione, and 2,4-hexanedione were reduced to the corresponding alcohols with high enantiomeric purities (>98% ee). The reductase showed high specificity constants (kcat/Km = 103-105 s-1 M-1) and relatively low Michaelis constants (Km = 10-4-10-3 M) for all the substrates examined.

    DOI: 10.1021/jo980165e

    Scopus

    researchmap

  • Lipase-catalyzed kinetic resolution of 2-acyloxy-2- (pentafluorophenyl)acetonitrile

    Takashi Sakai, Yasushi Miki, Mayumi Nakatani, Tadashi Ema, Kenji Uneyama, Masanori Utaka

    Tetrahedron Letters   39 ( 29 )   5233 - 5236   1998年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The lipase-catalyzed kinetic resolution of (±)-2-acyloxy-2- (pentafluorophenyl)acetonitrile (±)-1 gave optically active cyanohydrin (S)- 2 and its antipodal ester (R)-1 (E = 211), the former of which was transformed (TBSOTf, DMAP) into its TBS-ether (S)-3, a new fluorinated chiral building block, and into naproxen ester 4 for X-ray analysis to determine the absolute configuration.

    DOI: 10.1016/S0040-4039(98)01029-6

    Scopus

    researchmap

  • Origin of the Enantioselectivity of Lipases Explained by a Stereo-Sensing Mechanism Operative at the Transition State

    Tadashi Ema, Juka Kobayashi, Soichi Maeno, Takashi Sakai, Masanori Utaka

    Bulletin of the Chemical Society of Japan   71 ( 2 )   443 - 453   1998年2月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The stereoelectronic considerations and the molecular modeling using an X-ray structure of Rhizomucor miehei lipase suggested that the lipase-catalyzed reactions proceed under the stereoelectronic control. This suggestion was supported by the semiempirical MO (MNDO-PM3) calculations carried out on the imidazole-catalyzed transesterification as a model reaction. The stereoelectronic effect operates at the transition state (TS) more effectively than at the tetrahedral intermediate (THI). The stabilization energy due to the stereoelectronic effect operating at the TS was estimated to be ca. 5 kcal mol-1. The enantioselectivities for 1-phenylethanol, l-phenyl-2-propanol, and 1-cyclohexylethanol were estimated in terms of the lipase-induced strain caused at the TS. A TS model generally applicable to chiral secondary alcohols is proposed. The kinetic study supported the TS model. The result that the enantioselectivity in the lipase-catalyzed transesterifications arises from the difference in Vmax between the two enantiomers rather than from the difference in Km indicates that the ability of Upases to discriminate between the enantiomers at the TS is high, while the ability to recognize the chirality in the binding step is poor. Furthermore, the difference in Vmax between the enantiomers was found to result not from the enhanced reactivity of the (R)-enantiomers but from the reduced reactivity of the (S)-enantiomers.

    DOI: 10.1246/bcsj.71.443

    Scopus

    researchmap

  • Enhancement of the Enantioselectivity in Lipase-Catalyzed Kinetic Resolutions of 3-Phenyl-2H-azirine-2-methanol by Lowering the Temperature to -40°C

    Takashi Sakai, Isamu Kawabata, Tetsuo Kishimoto, Tadashi Ema, Masanori Utaka

    Journal of Organic Chemistry   62 ( 15 )   4906 - 4907   1997年7月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/jo970581j

    Scopus

    researchmap

  • Highly regio- and enantioselective reduction of 1-chloro-2,4-alkanediones using baker's yeast: Effects of organic solvents as additives

    Jing Nan Cui, Ryoji Teraoka, Tadashi Ema, Takashi Sakai, Masanori Utaka

    Tetrahedron Letters   38 ( 17 )   3021 - 3024   1997年4月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Bakers' yeast reduction of 1-chloro-2,4-alkanediones 1a afforded 1-chloro-2-hydroxy-4-alkanones 2a regioselectively with low optical purities. Application of inhibitors and heat-treatment of bakers' yeast enhanced the optical purities toward the S enantiomer (88-91% ee). Organic solvents added in small amounts were also found to enhance the S selectivity significantly. High optical purities 94-96% ee were achieved by the combined action of the inhibitor, heat-treatment, and organic solvent.

    DOI: 10.1016/S0040-4039(97)00524-8

    Scopus

    researchmap

  • Lipase-catalyzed efficient kinetic resolution of 3-Hydroxy-3-(pentafluorophenyl)propionitrile

    Takashi Sakal, Tetsuo Takayama, Takafumi Ohkawa, Osamu Yoshio, Tadashi Ema, Masanori Utaka

    Tetrahedron Letters   38 ( 11 )   1987 - 1990   1997年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Efficient kinetic resolution of racemic 3-hydroxy-3-(pentafluorophenyl)- propionitrile (±)-1 by a lipase-catalyzed transesterification gave optically pure (S)-3-hydroxy-3-(pentafluorophenyl-)propionitrile (S)-1 and (R)-(+)-3-acetoxy-3-(penta-fluorophenyl)propionitrile (R)-1 [>99% ee, respectively, E = 1057], the former of which was further transformed into (S)-(-)-3-amino-1-(pentafluorophenyl)-1-propanol (S)-7 in four steps.

    DOI: 10.1016/S0040-4039(97)00255-4

    Scopus

    researchmap

  • New optically active diporphyrin having a chiral cyclophane as a spacer

    Tadashi Ema, Shigeharu Misawa, Shuichi Nemugaki, Takashi Sakai, Masanori Utaka

    Chemistry Letters   ( 6 )   487 - 488   1997年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Optically active dimeric porphyrin covalently linked by a chiral cyclophane was synthesized; the two porphyrin chromophores were disposed in a slipped cofacial fashion, which was found to be tunable by cooperative coordination of diamines with various chain lengths.

    DOI: 10.1246/cl.1997.487

    Scopus

    researchmap

  • Kinetic resolution of racemic 2-substituted 3-cyclopenten-1-ols by lipase-catalyzed transesterifications: A rational strategy to improve enantioselectivity

    Tadashi Ema, Soichi Maeno, Yusuke Takaya, Takashi Sakai, Masanori Utaka

    Journal of Organic Chemistry   61 ( 24 )   8610 - 8616   1996年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The effect of the acyl group of acylating agents on the enantioselectivity in the Pseudomonas cepacia lipase-catalyzed acylations of racemic alcohols has been studied. 2-[(N,N-Dimethylcarbamoyl)-methyl]-3-cyclopenten-1-ol (1) and 2-[2-(tert-butyldimethylsilyloxy)ethyl]-3-cyclopenten-1-ol (4) were resolved with a variety of enantioselectivities. In the case of alcohol 1, the enantiomeric ratio (the E value) was increased by changing the acylating agent from vinyl acetate (E = 30) to vinyl butyrate (E = 156) and dropped substantially with longer acyl donors. With vinyl chloroacetate, the reaction rate was fast and the enantioselectivity was high (E = 89), whereas the resolution with vinyl trifluoroacetate resulted in a very poor enantioselectivity (E = 4). The bulky acylating agent, vinyl pivalate, gave a moderate enantioselectivity (E = 15). In the case of alcohol 4, the enantioselectivities were excellent (E > 142) except vinyl pivalate (E = 12). It is indicated that the acyl group transiently attached at the active site of the lipase acts as a stereochemical controller. The solvent effect is also described briefly. A clear correlation was observed between the E values and the log P values of the organic solvents; the smaller the log P value of the solvent, the higher the E value.

    DOI: 10.1021/jo961144s

    Scopus

    researchmap

  • Significant effect of acyl groups on enantioselectivity in lipase-catalyzed transesterifications

    Tadashi Ema, Soichi Maeno, Yusuke Takaya, Takashi Sakai, Masanori Utaka

    Tetrahedron Asymmetry   7 ( 3 )   625 - 628   1996年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The effect of the acyl group of acylating agents on the enantioselectivity in the lipase-catalyzed transesterification of racemic 2-[(N,N-dimethylcarbamoyl)methyl]-3-cyclopenten-1-ol in diisopropyl ether was found to be significant. The enantioselectivity was enhanced markedly by changing the acylating agent from vinyl acetate to vinyl butyrate, and dropped substantially with longer acyl donors. Other acyl donors were also examined.

    DOI: 10.1016/0957-4166(96)00049-3

    Scopus

    researchmap

  • Highly efficient and convenient regeneration of NADPH for asymmetric reduction using bakers' yeast cell free extract

    Masanori Utaka, Tomoko Yano, Ema Tadashi, Takashi Sakai

    Chemistry Letters   ( 12 )   1079 - 1080   1996年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    An asymmetric reduction of ethyl pyruvate was carried out using bakers' yeast cell free extract with addition of NADPH in catalytic amounts and glucose as a hydride source. The total turnover number of NADPH reached 7680. The efficiency of the cell free extract is discussed.

    DOI: 10.1246/cl.1996.1079

    Scopus

    researchmap

  • Unusual picosecond 1(π, π*) deactivation of ruffled nonplanar porphyrins

    Steve Gentemann, Craig J. Medforth, Tadashi Ema, Nora Y. Nelson, Kevin M. Smith, Jack Fajer, Dewey Holten

    Chemical Physics Letters   245 ( 4-5 )   441 - 447   1995年11月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Time-resolved and steady-state optical data are presented for metal-free meso-tetraalkylporphyrins, H2T(alkyl)P. Introduction of bulky tertiary-butyl or adamantyl substituents at the meso positions induces large ruffling distortions of the macrocycle skeleton that give rise to highly novel photophysical properties of the porphyrins. These include ultrashort 1(π, π*) lifetimes of 10-50 ps at 296 K that, intriguingly, lenghten to 10-15 ns at 78 K, the typical timescale found at both temperatures for planar derivatives such as tetra(n-pentyl) and tetraphenyl porphyrins. The ability of the nonplanar ruffled porphyrins to undergo additional structural deformations in the excited singlet state likely underlies their dramatically enhanced rates of internal conversion. © 1995.

    DOI: 10.1016/0009-2614(95)01030-D

    Scopus

    researchmap

  • Molecular recognition: New chiral metalloporphyrins as receptor models

    Hisanobu Ogoshi, Tadashi Ema, Yusuke Kato, Tadashi Mizutani, Yasuhisa Kuroda

    Supramolecular Chemistry   6 ( 1-2 )   115 - 124   1995年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    New chiral metalloporphyrins capable of multi-point recognition are prepared and their recognition behavior, especially chiral recognition, is studied. The first part of the paper is concerned with general formalism for multi-point recognition, where uniqueness of multi-point recognition, isolation of interaction in terms of free energy, enthalpy and entropy, and the meaning of these thermodynamic parameters are discussed. Enantioselective binding of amino acid esters to two new chiral porphyrins is investigated by UV-vis, NMR and IR spectroscopic methods. Chiral recognition is achieved by combination of three recognition interactions between host and guest. © 1995, Taylor & Francis Group, LLC. All rights reserved.

    DOI: 10.1080/10610279508032527

    Scopus

    researchmap

  • Synthesis and CD spectrum of chiral porphyrin dimer

    Tadashi Ema, Shuichi Nemugaki, Sadao Tsuboi, Masanori Utaka

    Tetrahedron Letters   36 ( 33 )   5905 - 5908   1995年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Chiral porphyrin dimer 1 was synthesized. The UV-vis spectrum of 1 was almost identical with that of the corresponding monomer 2. The circular dichroism induced in the Soret region of 1 was very strong and of the split type due to the chiral exction coupling. © 1995.

    DOI: 10.1016/00404-0399(50)11388-

    Scopus

    researchmap

  • Restricted internal rotation of amino acid esters. Quantitative evaluation of rigidity of a molecule in terms of internal rotation entropy

    Tadashi Mizutani, Tadashi Ema, Hisanobu Ogoshi

    Tetrahedron   51 ( 2 )   473 - 484   1995年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    As a model of molecular recognition of a flexible guest through multi-point recognition, the two-point fixation of the NH2 group and the C=O group of amino acid esters to porphyrin host was investigated from thermodynamic point of view. The negative entropy change owing to restriction of internal rotation around the Cα-C(carbonyl) bond of guest as driven by the two-point fixation was calculated from the following steps: (1) ab initio molecular orbital calculations at the 3-21G level to generate a potential energy surface for internal rotation along the Cα-C(carbonyl) bond and the Cα-Cβ bond, and (2) a calculation of partition function of the system based on classical statistical mechanics. The entropy loss due to the restriction of a rotation around the Cα-C(carbonyl) bond was 5.0 cal·K-1·mol-1 for alanine methyl ester and 1.9 cal·K-1·mol-1 for valine methyl ester, indicating that valine methyl ester is more rigid with respect to the Cα-C(carbonyl) rotation. This entropy loss was found to originate from the correlated rotation of the Cα-C(carbonyl) bond and the Cα-Cβ bond. © 1994.

    DOI: 10.1016/0040-4020(94)00909-E

    Scopus

    researchmap

  • Crystal structure of a remarkably ruffled nonplanar porphyrin (pyridine)[5,10,15,20-tetra(tert-butyl)porphyrinato]zinc(II)

    Mathias O. Senge, Tadashi Ema, Kevin M. Smith

    Journal of the Chemical Society, Chemical Communications   ( 7 )   733 - 734   1995年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    The title compound presents the first example of a sterically ruffled porphyrin bearing only meso substituents; the degree of ruffling is severe, with Cm-displacements of up to 1 Å.

    DOI: 10.1039/C39950000733

    Scopus

    researchmap

  • Ruffling in a Series of Nickel(II) meso-Tetrasubstituted Porphyrins as a Model for the Conserved Ruffling of the Heme of Cytochromes c

    W. Jentzen, M. C. Simpson, J. D. Hobbs, X. Song, J. A. Shelnutt, T. Ema, N. Y. Nelson, C. J. Medforth, K. M. Smith, M. Veyrat, M. Mazzanti, R. Ramasseul, J. C. Marchon, T. Takeuchi, W. A. Goddard

    Journal of the American Chemical Society   117 ( 45 )   11085 - 11097   1995年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Metalloporphyrins undergo remarkable nonplanar distortions of the macrocycle that perturb the chemical and photochemical properties of these important protein cofactors. Further, the tertiary structure of the surrounding protein can manipulate these distortions as a means of regulating biological function. For cytochromes c, for example, an energetically unfavorable, conserved nonplanar distortion of the heme exists and likely plays a role in its electrontransfer function. The heme distortion is primarily of the ruffling (ruf) type (corresponding to the lowest frequency B1u-symmetry normal mode) in which the pyrroles are twisted about the metal–Npyrrole bond. This B1u-symmetry nonplanar distortion is commonly observed in metalloporphyrin crystal structures, as are the saddling (sad) B2u-symmetry distortion, waving (wav) Eg-symmetry distortions, and doming (dom) A2u-symmetry distortion. Each of these nonplanar distortions is expected to result in unique alterations of the chemical and physical properties of the nominally planar porphyrin macrocycle. Symmetrical porphyrin substitution with tetrahedrally bonded atoms at the four meso bridging carbons generally results in the B1u ruffling distortion; therefore, we investigated a series of meso-tetrasubstituted porphyrins for which the substituents vary in size (methyl, ethyl, propyl, pentyl, isopropyl, cyclopropyl derivative 11a, cyclohexyl, apopinenyl (10), tert-butyl, adamantyl), increasing the steric crowding at the periphery. Molecular mechanics calculations show increasing degree of ruffling (CαNNCα angle for opposite pyrroles varies from 0 to 57°) for this series of porphyrins, generally agreeing with the X-ray structures that are available. In addition, the frequencies of the structure-sensitive Raman lines decrease nonlinearly with increasing ruffling angle. The localization of the B1u nonplanar distortion in only the Cα-Cm bond torsion (not the case for the B2u sad distortion) suggests a means by which the B1u distortion might be distinguished from other types of nonplanar distortion by using resonance Raman spectroscopy. Also, the size of the red shifts in the π → π* absorption bands depends on Cα–Cm torsion angle in a nonlinear fashion and the shift is accurately predicted by INDO/s molecular orbital calculations when the nonplanar structures obtained from molecular mechanics are used. © 1995, American Chemical Society. All rights reserved.

    DOI: 10.1021/ja00150a008

    Scopus

    researchmap

  • 5,10,15,20‐Tetra‐tert‐butylporphyrin and Its Remarkable Reactivity in the 5‐ and 15‐Positions

    Tadashi Ema, Mathias O. Senge, Nora Y. Nelson, Hisanobu Ogoshi, Kevin M. Smith

    Angewandte Chemie International Edition in English   33 ( 18 )   1879 - 1881   1994年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Owing to the steric bulk of the tert‐butyl groups, the reactivity of the novel porphyrin 1, which has a nonplanar macrocyclic framework, deviates distinctly from that of any other known porphyrin. For example, prolonged treatment of 1 in HClO4/MeOH leads to formation of 5,15‐dihydroporphyrin (“porphodi‐methene”) 2. (Figure Presented.) Copyright © 1994 by VCH Verlagsgesellschaft mbH, Germany

    DOI: 10.1002/anie.199418791

    Scopus

    researchmap

  • Mechanism of Induced Circular Dichroism of Amino Acid Ester-Porphyrin Supramolecular Systems. Implications to the Origin of the Circular Dichroism of Hemoprotein

    Tadashi Mizutani, Tadashi Ema, Takashi Yoshida, Thomas Renné, Hisanobu Ogoshi

    Inorganic Chemistry   33 ( 16 )   3558 - 3566   1994年8月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Circular dichroism (CD) spectra of the complexes between metalloporphyrins and chiral amino acid derivatives exhibited either split type induced CD or single peak induced CD in the Soret region depending on the host-guest combination. Systematic studies on the complexation of amino acid derivatives by porphyrin hosts indicate that intermolecular hydrogen bonding to the carbonyl group of the guest is necessary for the split type induced CD to occur. Molecular orbital calculations of the rotational strength of a porphyrin-amino acid ester complex by the MNDO method predict that the ICD of porphyrin-amino acid ester complexes is determined by the relative geometry of the carbonyl group and the porphyrin plane. The relative geometry of the chromophores expected from the X-ray crystallographic analysis of a complex between leucine methyl ester and a similar host then gives split type induced CD, in agreement with experiment. These experimental and theoretical results indicate that the coupling between the magnetic transition dipole moment (mj) and the electric transition dipole moment (μj) of a carbonyl group and the electric transition dipole moment (μi) of the porphyrin Soret band makes an important contribution to the observed induced CD. © 1994, American Chemical Society. All rights reserved.

    DOI: 10.1021/ic00094a020

    Scopus

    researchmap

  • Design and Synthesis of a Trifunctional Chiral Porphyrin with C<inf>2</inf> Symmetry as a Chiral Recognition Host for Amino Acid Esters

    Tadashi Mizutani, Tadashi Ema, Takashi Tomita, Yasuhisa Kuroda, Hisanobu Ogoshi

    Journal of the American Chemical Society   116 ( 10 )   4240 - 4250   1994年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    An intrinsic chiral recognition host, (R,R)- or (S,S)-[trans-5,15-bis(2-hydroxyphenyl)-10-{2,6-bis((methoxycarbonyl)methyl)phenyl}-2,3,17,18-tetraethylporphyrinato]zinc(II) (1), was synthesized by the coupling between (3,3',4,4'-tetraethyl-5,5'-bis(α-hydroxy-2-methoxybenzyl)-2,2'-dipyrryl)methane (8) and dimethyl 2-(bis(2-pyrryl)-methyl)-l,3-benzenediacetate (16). This pyrrylmethanol method made it possible to perform the regiospecific coupling between differently functionalized dipyrromethane units. Host 1 was designed to have three recognition elements: metal coordination, hydrogen bond donor, and hydrogen bond acceptor (and/or steric repulsion) groups. These groups are arranged in a convergent fashion, forming a chiral recognition pocket. Host 1 was resolved into two enantiomers, (+)-1 and (-)-1. The binding constants in CHC13 were determined by UV-vis titration. Host (+)-1 was found to show an enantioselectivity of 2.0-2.8 in respect to l- and d-enantiomers of I1e-OMe, Leu-OMe, Leu-OBzl, Val-OMe, Pro-OMe, and Phe-OMe. Host (+)-1 showed an enantioselectivity of 0.47 in respect to l- and d-enantiomers of serine benzyl ester, indicating that the enantioselectivity was reversed. Reference porphyrins 2-4, which lack some of recognition groups, were also synthesized by the pyrrylmethanol method to clarify the roles of the recognition groups of (+)-1 in thermodynamics of the binding processes. Total free energy change upon binding of l- and d-Ile-OMe to host (+)-l (ΔG°total for L, -5.05, and d, -4.46 kcal/mol) was separated into three terms: metal coordination energy (ΔG°Zn)>-4.15 kcal/mol; hydrogen bond energy (ΔΔG°OH),-1.30 kcal/mol; and steric repulsion energy (ΔΔG°LCOOMe or ΔΔG°DcooMe), +0.40 kcal/mol for l- and +0.99 kcal/mol for d-Ile-OMe. The third recognition group (CH2CO2Me) of (+)-l was found to destabilize the complexes due to steric repulsions. In contrast, the CH2CO2Me group was found to stabilize the complex between d-Ser-OBzl and (+)-l, suggesting that hydrogen bonding between the OH group of serine and the C=O group of (+)-l takes place. On the basis of these thermodynamic studies, chiral recognition was found to be achieved by cooperative functions of these three recognition groups. © 1994, American Chemical Society. All rights reserved.

    DOI: 10.1021/ja00089a013

    Scopus

    researchmap

  • Recognition of α-Amino Acid Esters by Zinc Porphyrin Derivatives via Coordination and Hydrogen Bonding Interactions. Evidence for Two-Point Fixation from Thermodynamic and Induced Circular Dichroism Spectroscopic Studies

    Tadashi Mizutani, Tadashi Ema, Takashi Yoshida, Yasuhisa Kuroda, Hisanobu Ogoshi

    Inorganic Chemistry   32 ( 10 )   2072 - 2077   1993年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Association constants between [trans-5,15-bis(2-hydroxy-1-naphthyl)-2,3,7,8,12,13,17,18-octaethylporphyrinato]-zinc(II) (1) and a series of α-amino acid esters (RCHNH2CO2CH3) were determined in chloroform by use of a UV-vis titration method. Association constants increased in the order Ala-OMe < Gly-OMe < Val-OMe < Leu-OMe, showing a preference for bulky amino acid esters. Contributions from the metal coordination and hydrogen bonding interactions to the total free energy change were estimated by use of reference compounds having no hydrogen bonding site. The free energy change for the binding of Leu-OMe to 1 in chloroform at 15 °C was −5.3 kcal/mol, which was separated into two contributions, (1) the metal coordination interaction ΔGMC = −3.8 kcal/mol and (2) the hydrogen bonding interaction ΔGHB = −1.5 kcal/mol. Circular dichroism (CD) induced in the porphyrin Soret band of 1 by complexation with optically active amino acid esters was of the split type for all the amino acid esters examined, whereas induced CD of a reference host, [trans-5,15-bis(2-methoxy-1-naphthyl)-2,3,7,8,12,13,17,18-octaethylporphyrinato]zinc(II) (2), was reduced in intensity and not of the split type. We found that the fixation of the carbonyl group of the guest by two-point recognition caused marked enhancements in induced CD. We suggest that the induced CD of 1 was caused by the coupling between the magnetic transition dipole moment of the carbonyl group of guest and the electric transition dipole moment of the Soret band of host. © 1993, American Chemical Society. All rights reserved.

    DOI: 10.1021/ic00062a032

    Scopus

    researchmap

  • Recognition of chirality and residual groups of amino acid esters using new trifunctional chiral porphyrins with C<inf>2</inf> symmetry

    Tadashi Mizutani, Tadashi Ema, Takashi Tomita, Yasuhisa Kuroda, Hisanobu Ogoshi

    Journal of the Chemical Society, Chemical Communications   ( 6 )   520 - 522   1993年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    An intrinsic chiral recognition host, [trans-5,15-bis(2-hydroxyphenyl)-10- {2,6-bis(methoxycarbonylmethyl)phenyl}-2,3,17,18-tetraethylporphyrinato]zinc(II) 1, is synthesized and found to show an enantioselectivity of ca. 2: 1 for L- and D-amino acid esters having non-polar residues, whereas it shows a reversed enantioselectivity of ca. 1: 2 for L- and D-Ser-OBzl.

    DOI: 10.1039/C39930000520

    Scopus

    researchmap

  • Synthesis and Photoreaction of 1,2,3,4-Tetra-t-butylnaphthalene: A Highly Crowded Naphthalene Derivative and Its Valenceisomers

    Sadao Miki, Tadashi Ema, Rie Shimizu, Hiroshi Nakatsuji, Zen ichi Yoshida

    Tetrahedron Letters   33 ( 12 )   1619 - 1620   1992年3月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    1,2,3,4-Tetra-t-butylnaphthalene (2), a highly crowded naphthalene derivative, has been synthesized. Upon irradiation, 2 underwent photovalence isomerization to afford 1,2,5,6-tetra-t-butyl-3,4-benzo-3-tricyclo[3.1.0.02,6]-hexene (3). The synthesis of 1,4,5,6-tetra-t-butyl-2,3-benzo-2,5-bicyclo[2.2.0]hexadiene (1), which was used for the synthesis of 2, is also described. © 1992.

    DOI: 10.1016/S0040-4039(00)91689-7

    Scopus

    researchmap

  • Selective syntheses of unsymmetrical meso-arylporphyrins

    Tadashi Ema, Yasuhisa Kuroda, Hisanobu Ogoshi

    Tetrahedron Letters   32 ( 35 )   4529 - 4532   1991年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    A selective synthetic route to unsymmetrical meso-arylporphyrins is described. New hybrid type of unsymmetrical porphyrin with C2v symmetry was prepared according to the new method. © 1991.

    DOI: 10.1016/0040-4039(91)80031-Z

    Scopus

    researchmap

▼全件表示

書籍等出版物

  • ドラマチック有機合成化学 : 感動の瞬間100

    有機合成化学協会( 担当: 分担執筆 ,  範囲: 二官能性ポルフィリン金属錯体触媒の開発−15年を経て恩師直伝の知恵を使う)

    化学同人  2023年7月  ( ISBN:9784759823363

     詳細を見る

    総ページ数:xiv, 206p   記述言語:日本語

    CiNii Books

    researchmap

  • Practical Methods for Biocatalysis and Biotransformations 3

    Wiley  2016年 

     詳細を見る

  • 有機合成実験法ハンドブック(第2版)

    有機合成化学協会  2015年 

     詳細を見る

  • Practical Methods for Biocatalysis and Biotransformations

    Wiley  2010年 

     詳細を見る

  • 酵素利用技術大系:基礎・解析から改変・高機能化・産業利用まで

    エヌ・ティー・エス  2010年 

     詳細を見る

  • 超分子サイエンス〜基礎から材料への展開〜

    エヌ・ティー・エス  2009年 

     詳細を見る

▼全件表示

MISC

  • Macrocyclic multinuclear metal complexes acting as catalysts for organic synthesis

    Bikash Dev Nath, Kazuto Takaishi, Tadashi Ema

    Catalysis Science and Technology   10 ( 1 )   12 - 34   2020年

     詳細を見る

    掲載種別:書評論文,書評,文献紹介等  

    Metal clusters in nature and artificial systems are known to exhibit excellent catalytic activities. Among various coordination systems, macrocyclic multinuclear metal complexes have unique structural features and great potential in organic synthesis. The multiple metal centers in a macrocyclic framework act as specific sites for the binding and activation of substrates, showing high catalytic activity and selectivity as a result of the cooperative effect of the multiple metal centers and robustness originating from macrocyclic skeletons. Most of them are precisely designed and synthesized, while occasionally, nice complexes also emerge from a fortuitous combination of metal ions and ligands. Here we overview the recent achievements of (i) multinuclear metal complexes with a covalently-linked macrocyclic ligand (category A), (ii) multinuclear metal complexes forming a macrocyclic skeleton (category B), and (iii) self-assembled supramolecular coordination complexes (category C). Various organic reactions catalyzed by these coordination systems are summarized here.

    DOI: 10.1039/c9cy01894h

    Scopus

    researchmap

  • Recent progress in catalytic conversions of carbon dioxide

    Chihiro Maeda, Yuki Miyazaki, Tadashi Ema

    Catalysis Science and Technology   4 ( 6 )   1482 - 1497   2014年6月

     詳細を見る

    掲載種別:書評論文,書評,文献紹介等  

    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. This journal is © the Partner Organisations 2014.

    DOI: 10.1039/c3cy00993a

    Scopus

    researchmap

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

    Tadashi Ema

    Tetrahedron Asymmetry   15 ( 18 )   2765 - 2770   2004年9月

     詳細を見る

    掲載種別:書評論文,書評,文献紹介等  

    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. © 2004 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetasy.2004.06.055

    Scopus

    researchmap

  • Mechanism of enantioselectivity of lipases and other synthetically useful hydrolases

    Tadashi Ema

    Current Organic Chemistry   8 ( 11 )   1009 - 1025   2004年7月

     詳細を見る

    掲載種別:書評論文,書評,文献紹介等  

    Lipases are biocatalysts most widely used in organic synthesis. Unusual but attractive feature of lipases is that, in addition to high catalytic activity and thermostability in organic solvents, lipases show high enantioselectivity and broad substrate specificity simultaneously. They show excellent enantioselectivity especially toward a wide range of secondary alcohols. The mechanistic details or stereoselective organic reactions are relatively well understood, and knowledge has been used to develop new chemical reagents. In contrast, biocatalysts are behind chemical reagents in rational design approaches, which is partly due to the mechanistic ambiguity or enzymatic reactions. The mechanistic aspects of enantioselective biocatalysts are nevertheless becoming clear. This review provides an overview of the studies aimed at understanding the mechanisms of enantioselectivity of synthetically useful hydrolases such as lipases, subtilisins and chymotrypsins toward unnatural chiral substrates. Several methods for addressing the mechanism are introduced: (i) substrate mapping, (ii) X-ray crystallographic analysis, (iii) computational calculations, (iv) kinetic analysis, (v) thermodynamic analysis, (vi) site-directed or random mutagenesis, (vii) spectroscopic methods such as fluorescence, ESR, and mass spectroscopy. Different models and mechanisms proposed so far are selected and explained. The chemical principles revealed by the mechanistic studies will be useful for (i) using the enzymes in organic synthesis efficiently, (ii) altering the features or the enzymes rationally, (iii) utilizing them as a tool for determining the absolute stereochemistry of molecules, and (iv) designing new artificial catalysts mimicking the catalytic machinery of the enzymes. © 2004 Bentham Science Publishers Ltd.

    DOI: 10.2174/1385272043370230

    Scopus

    researchmap

受賞

  • 日本化学会 学術賞

    2022年  

     詳細を見る

  • 長瀬科学技術振興財団 長瀬研究振興賞

    2021年  

     詳細を見る

  • 八雲環境科学振興財団 八雲賞

    2020年  

     詳細を見る

  • 有機合成化学協会 企業冠賞「東ソー・環境エネルギー賞」

    2020年  

     詳細を見る

  • 科研費審査委員表彰

    2017年  

     詳細を見る

    受賞国:日本国

    researchmap

  • 岡山工学振興会 内山勇三科学技術賞

    2012年  

     詳細を見る

    受賞国:日本国

    researchmap

  • 岡山リサーチパーク研究・展示発表会 産学官連携推進賞

    2011年  

     詳細を見る

    受賞国:日本国

    researchmap

  • HGCS Japan Award of Excellence 2011

    2011年  

     詳細を見る

    受賞国:日本国

    researchmap

  • 岡山工学振興会 科学技術賞

    2008年  

     詳細を見る

    受賞国:日本国

    researchmap

  • 日本化学会第85春季年会「若い世代の特別講演会」講演証

    2005年  

     詳細を見る

    受賞国:日本国

    researchmap

  • 日本化学会生体機能関連化学部会(18回)・バイオテクノロジー部会(7回)合同シンポジウム 部会講演賞

    2003年  

     詳細を見る

    受賞国:日本国

    researchmap

  • 有機合成化学協会中国四国支部 奨励賞

    1999年  

     詳細を見る

    受賞国:日本国

    researchmap

▼全件表示

共同研究・競争的資金等の研究

  • 協同効果を利用する精密制御反応場:多官能性ポルフィリン金属錯体

    研究課題/領域番号:16H01030  2016年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    依馬 正

      詳細を見る

    配分額:6240000円 ( 直接経費:4800000円 、 間接経費:1440000円 )

    異なる長さのメチレン鎖をリンカーとした4種類のZnポルフィリン錯体を合成したところ、メチレン鎖長に依存してポルフィリンの構造やスペクトルが変化した。これらの触媒とテトラブチルアンモニウムハライド(共触媒)を用いて、エポキシドの速度論的光学分割を行ったところ、触媒活性やエナンチオ選択性もメチレン鎖長に依存して変化した。さらに、架橋部位にトリアゾリウム塩を組み込んだキラル二官能性Znポルフィリン錯体を合成し、速度論的光学分割に用いた。二つの官能基による協同効果のため触媒活性が向上し、室温でも速度論的光学分割反応が進行した。この触媒のメチレン鎖長とトリアゾリウム塩の対アニオンを最適化した後、最適触媒を用いて反応条件を最適化し、基質適用範囲を調査した。
    二官能性Alポルフィリン錯体を用いると、シクロヘキセンオキシドと二酸化炭素の交互共重合が進行した。高い触媒活性(TOF = 17,000 h-1)と選択性(>99%)を示し、生成物はほぼポリカーボネートのみであった。比較的分子量が大きいポリカーボネート(約33,000g/mol)が得られた。GPCの結果、二峰性(bimodal)のピークが観測されたため、それぞれについて、数平均分子量(Mn)、多分散度(Mw/Mn)及びポリマー鎖数(1触媒あたり)を算出した。各ピークの多分散度(Mw/Mn)が極めて小さい(1.03)ことから、鎖長の揃ったポリマーが生成していた。各ピークにおいて、触媒1分子によって合成されたポリマー鎖数が23~108本存在していて、連鎖移動反応が進行して、触媒の利用効率が高いことも分かった。
    新たな配位子を設計し金属イオンと混ぜて加熱したところ、ユニークな大環状型多核金属錯体が得られた。上記のタイプの触媒として機能することも確認した。

    researchmap

  • Mnクラスターの形成を促進する超分子配位システム

    研究課題/領域番号:15K13745  2015年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    依馬 正, 前田 千尋, 高石 和人

      詳細を見る

    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    2つの水分子を4電子酸化して酸素分子を与える光化学系IIの酸素発生中心(Mnクラスター)は、光合成における心臓部である。本研究ではこれによく似たMnクラスターを合成するための超分子戦略として、Mnクラスターに対して3つのカルボキシラート基を真横から配位させ系統的な構造チューニングが可能な超分子配位システムを構築する。6つのピリジン部位を有するテンプレート分子を用いたクロスカップリング反応を駆使して、ポルフィリン単量体から大環状ポルフィリン六量体を収率53%で合成することに成功した。同様に、大環状ポルフィリン四量体を収率14%で合成した。種々の分光学的・光物性測定によりこれらの特徴を精査した。

    researchmap

  • カルバゾール骨格を組み込んだポルフィリン多量体の構築

    研究課題/領域番号:15K05427  2015年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    前田 千尋, 依馬 正, 高石 和人, 戸高 匠, 上田 知美, 田中 祐美, 永幡 敬治

      詳細を見る

    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    ポルフィリン類縁体は光化学、電気化学、超分子化学など様々な分野で注目されている色素である。我々はカルバゾールを組み込んだ縮環ポルフィリンの開発に成功してした。カルバゾールのベンゾ環の縮環により共役系が大きく拡張するため興味深い電子的性質を示す。本研究ではカルバゾール骨格を有するポルフィリン多量体を合成し、多量体内の縮環ポルフィリン間での電子的相互作用について明らかにした。またカルバゾール骨格を組み込んだジピリンも新規に開発し、それらの物性評価と多量化について検討した。

    researchmap

  • 含窒素複素環式カルベンを有する人工生体触媒の創成と有機合成への応用

    研究課題/領域番号:25288078  2013年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    依馬 正

      詳細を見る

    配分額:17940000円 ( 直接経費:13800000円 、 間接経費:4140000円 )

    炭素-炭素結合形成反応を触媒できる人工生体触媒を創成した。リパーゼの活性中心セリン残基と結合させるためにリン酸エステルを連結したNHC前駆体1を13段階で合成した。1をリパーゼに混ぜて両者が連結した人工生体触媒CALB-1を得た。ベンズアルデヒドのベンゾイン反応を触媒した。
    変異導入でリパーゼのイソロイシン287をシステインに置換したI287C変異体を化学修飾した。
    無溶媒でNHC触媒反応を行うと従来より少ない触媒量でも反応が進行することを発見した。触媒的な固体-液体又は固体-固体変換反応も進行した。固体-固体変換反応においては、固体混合物が部分的に融けた半固相状態を経由して反応が進行した。

    researchmap

  • C-C結合形成反応を触媒できる人工生体触媒の創製

    研究課題/領域番号:23655157  2011年 - 2012年

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    依馬 正

      詳細を見る

    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    酵素(リパーゼ)に含窒素複素環式カルベン(N-heterocyclic carbene, NHC)有機触媒を化学修飾した人工生体触媒を創製し、それを用いてエナンチオ選択的なC-C結合形成反応を実施した。NHCは、変異導入部位(システイン)もしくは活性部位に導入した。ベンゾイン反応を試したところ、反応が進行し、低いながらもエナンチオ選択性が発現した。

    researchmap

  • 高機能酵素変異体の創製と合成化学的応用

    研究課題/領域番号:20550152  2008年 - 2010年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    依馬 正

      詳細を見る

    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    汎用生体触媒であるリパーゼとカルボニル還元酵素を合理的変異導入あるいはランダム変異導入により進化させて高機能化するとともに、有用な光学活性化合物を不斉合成した。(1)苦手基質に対する触媒活性とエナンチオ選択性が同時に向上した二重変異体(I287F/I290A)リパーゼを創製し、その合成化学的有用性を実証した。(2)カルボニル還元酵素を用いてジフルオロメチレン基を有するβ-ケトエステルを高濃度不斉還元し、得られた光学活性アルコールを含フッ素β-アミノ酸誘導体へ変換した。

    researchmap

  • 汎用生体触媒の機構解明と機能制御

    研究課題/領域番号:17550155  2005年 - 2006年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    依馬 正

      詳細を見る

    配分額:3600000円 ( 直接経費:3600000円 )

    1.リパーゼのエナンチオ選択性の合理的制御
    メカニズムとX-線結晶構造に基づいて、burkholderia cepacia由来リパーゼのエナンチオ選択性を制御するための変異導入サイトを287番目のイソロイシンに決定した。位置指定変異導入により立体的嵩高さを上げて遅く反応するエナンチオマー(S-体)の反応性を押さえればエナンチオ選択性は向上し、逆に立体障害を取り除いてS-体の反応を促進すればエナンチオ選択性は低下すると予測した。種々の変異体を調製し、2種類の2級アルコールの速度論的光学分割を実施した。エナンチオ選択性はE値で評価した。287番目のアミノ酸の嵩高さとエナンチオ選択性(E値)の間には明らかな相関が確認され、合理的にエナンチオ選択性を制御(上げたり下げたり)することに成功した。
    2.リパーゼ反応を経由した光学活性ポルフィリン二量体の合成とその機能
    リパーゼ反応により得た光学的に純粋なポルフィリンアルコールをイソフタル酸で連結し二量体とし、その亜鉛ポルフィリンの不斉識別機能を確認した。
    3.遺伝子組換え大腸菌を用いたケトンの不斉還元
    幅広い範囲の基質に対して高いエナンチオ選択性を示すカルボニル還元酵素を高発現する組換え大腸菌を構築し、それを用いて20種類以上のケトンを不斉還元した。そのうち12種類において98% ee以上の光学純度のアルコールを得た。2,4-オクタンジオンに対する反応条件を最適化したところ、位置特異的かつ立体特異的に還元反応が進行し、対応するアルコールを41g/Lの生産性で単離した。その他、重要医薬品の中間体を高効率・高光学純度で不斉合成した。
    4.カルボニル還元酵素の単結晶作製に向けた実験
    N末端側及びC末端側にヒスチジンタグを有するカルボニル還元酵素の遺伝子を構築し、それを大腸菌にて発現させた。今後、酵素の単結晶を作製する。

    researchmap

  • 組織化ナノリアクターによる生体触媒の高機能化

    研究課題/領域番号:15550093  2003年 - 2004年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    依馬 正, 酒井 貴志, 是永 敏伸

      詳細を見る

    配分額:3800000円 ( 直接経費:3800000円 )

    多孔質セラミックスToyonite 200Mに固定化したリパーゼを用いて1,1-ジフェニル-2-プロパノールに対して高温下で反応させた。120℃でも反応が進行し光学的に純粋なエステル生成物を与えた。セライト固定リパーゼを用いた場合は100℃ですら全く反応しなかった。超臨界二酸化炭素中でも温度効果を調査したところ、80℃で変換率42%、E値211を得た。ポルフィリンを置換基として持つ2級アルコールに対しては60℃で最も効率よく反応し、得られたエステル並びにアルコールの光学純度は共に100%であった。
    リパーゼ変異体を多孔質セラミックスに固定化し、そのエナンチオ選択的アシル化を実施した。その際、メカニズムに基づいたエナンチオ選択性の人為的制御がどの程度可能かを調査した。その結果、活性部位近傍の1アミノ酸を別のアミノ酸で置換することにより、エナンチオ選択性は予想どおりの変化を示した。熱力学パラメータを算出したところ、エンタルピー駆動型でエナンチオ選択性が変化していることが明らかになった。
    固定化リパーゼを用いた2級アルコールの絶対配置決定法を開発した。異なる置換基を持つ2種類の1-置換エタノールに対するエナンチオ選択性(E値)を測定し、それらの置換基を両側に併せ持つ2級アルコールに対するE値と絶対配置を予測・決定した。20例中19例に対して予測と実験結果が一致し定量的にも良好な相関を示した。
    組換え大腸菌を用いて取得したカルボニル還元酵素を多孔質セラミックスに固定化し、それを用いて不斉還元を実施したが特に変化は認められなかった。むしろ、大腸菌中でカルボニル還元酵素と補酵素再生用酵素の遺伝子を共発現させて、全細胞系で反応させる方が簡便かつ効率よく光学活性アルコールを合成できた。16種類のケトンを還元したところ高エナンチオ選択的不斉還元反応が進行し、8例において98%ee以上の純度でアルコール体を与えた。

    researchmap

  • 多孔質セラミックス固定化酵素触媒の開発と光学活性含フッ素超分子材料の創製

    研究課題/領域番号:13555255  2001年 - 2003年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    酒井 貴志, 安井 茂男, 是永 敏伸, 依馬 正

      詳細を見る

    配分額:13600000円 ( 直接経費:13600000円 )

    (1)極低温下での高効率および高エナンチオ選択的リパーゼ光学分割反応の開発
    (a)セラミックスを担体とする固定化リパーゼ触媒の開発のために、セラミックスに取り付ける有機架橋剤の探索を行った。有機架橋剤とセラミックス部の結合は、末端のシラノール部との共有結合により固定化し、さらに他端の官能基としてイソ酪酸エステル基を用いた時、-30℃におけるエナンチオ選択性、触媒回転数が共に良い結果を与えることを見出した。
    (b)固定化リパーゼ触媒のさらなる高効率化のため、ラセミ体アルコールの光学分割反応に用いるアシル化反応剤の最適化検討を行った。アシル化剤としてブタン酸ビニルエステルを用い、-40℃における固定化リパーゼ触媒の活性およびエナンチオ選択性を調査した所、極低温化でも極めて高い触媒活性を維持したまま高いエナンチオ選択性を得ることに成功した。
    (2)リパーゼ光学分割反応を鍵とした含フッ素光学活性アミン化合物の合成及び超分子材料の開発
    (a)リパーゼ触媒を用いて、高光学純度のペンタフルオロフェニル置換のシアノヒドリンを調製し、それを鍵中間体として、ペンタフルオロフェニル基とフェニル基を同一分子内に有する新規不斉1,2-アミノアルコールの合成に成功した。この化合物のX線結晶解析を行った所、アルコール原子とペンタフルオロフェニル基の相互作用という珍しい現象を見出し、超分子材料の創製に対する新たな知見が得られた。
    (b)ペンタフルオロフェニル基を有するイミンのカップリング反応から、新規不斉1,2-ジアミンの合成に成功した。1,2-ジアミンに導入されたペンタフルオロフェニル基の影響により、ペンタフルオロフェニル基を導入したジアミンの塩基性はフェニル基類縁体に比べ大きく低下していることがわかり、ペンタフルオロフェニル基の窒素原子への電子求引効果の影響が判明した。

    researchmap

  • 光学活性高歪み化合物アジリン類の効率的調製と天然,非天然アミン,アミノ酸類の合成

    研究課題/領域番号:12450366  2000年 - 2002年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    酒井 貴志, 是永 敏伸, 依馬 正

      詳細を見る

    配分額:13100000円 ( 直接経費:13100000円 )

    アジリンメタノールに対して種々の試薬を反応させ、立体選択的な変換反応を開発した。中でも、AlMe_3を反応させて合成したアジリジンに対する立体選択的水素添加反応においては、3位選択的な開環反応が起こり、β-アミノアルコールのみが得られた。溶媒の種類に応じて3位の立体保持、立体反転がある程度の規則性をもって進行することが分かった。溶媒の比誘電率とジアステレオマー過剰率の間には相関関係が認められた。また、新規アジリンカルボン酸エステルの合成にも成功した。β-ケトエステルをヒドロキシアミンでオキシムへ誘導し、トシル化後にトリエチルアミンを添加するとアジリンが得られた。
    多孔質セラミックスに固定化したリパーゼを用いることにより、アジリンの速度論的光学分割の反応速度が著しく向上したが、エナンチオ選択性は低下した。これを克服するために、アシル化試薬の種類を検討したところ、エナンチオ選択性が上がる条件が見つかった。酪酸ビニルを用いたときE値=96で、触媒回転数は10倍以上になった。
    リパーゼを用いた光学分割において、反応温度を下げることによってエナンチオ選択性が向上することを以前に見出している。このときエナンチオ選択性は熱力学式に従って向上するが、ある温度以下になると、エナンチオ選択性は別の熱力学式に従って低下することが分かった。この温度を「転化温度」と呼ぶ。アジリンメタノールを基質とした反応において、溶媒を変えて調査したところ、溶媒の種類によって転化温度が異なることが判明した。更に、リパーゼの種類を変えても、異なる転化温度が得られた。転化温度と溶媒の種々のパラメータとの相関を調べた。基質の溶媒和状態を調べるために、低温NMR測定も行った。酵素及び基質が溶媒と複雑に影響しあった複合的要因により転化温度が決定されているものと考えられる。

    researchmap

  • ペンタフルオロフェニル基をもつ光学活性化合物の合成-その高次構造と機能の解明

    研究課題/領域番号:10555321  1998年 - 1999年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    宇高 正徳, 南井 正好, 依馬 正, 酒井 貴志

      詳細を見る

    配分額:12600000円 ( 直接経費:12600000円 )

    ペンタフルオロフェニル基(C_6F_5)は、電子吸引性基としてだけでなく、電子豊富な芳香環とのスタッキング相互作用を示すなど、ユニークな物性をもつことが知られているが、機能性物質として応用されるには至っていない。この化合物に不斉を導入すると不斉分子認識剤など、新たな機能の発現が期待できると考えられる。本研究において、リパーゼを用いた速度論的光学分割により高光学純度の(R)-および(S)-2-hydroxy-2-(pentafluorophenyl)acetonitrilre(1)をそれぞれ合成し、それらをジアステレオ選択的に光学活性1,2-ジオール類bis(pentafluorophenyl)ethane-1,2-diol、1-(pentafluorophenyl)-2-phenylethane-1,2-diolおよびβ-アミノアルコール類2-amino-1,2-bis(pentafluorophenyl)ethanol、2-amino-1-(pentafluorophenyl)-2-phenylethanolに変換することに成功した。すなわち、ラセミ体(±)-1をlipase LIPを用いて0℃で速度論的光学分割を行ったところ、高い光学純度で(R)-1(96%ee)とそのアセテート(S)-2(98%ee)を得ることができた。さらに(R)-1からthreo選択的にジオール(1R,2R)-体(94%ee)および(1R,2R)-体(87%ee)にそれぞれ選択的に変換することに成功した。本合成経路では、経由するイミン中間体のNaBH_4による還元反応が収率、ジアステレオ選択性を決める重要な鍵反応になっているが、系中にTMSClと水を加えることによって反応が促進され、さらにラセミ化を抑えることを見いだし、threo選択的に(1R,2R)-ジオールを84%eeで得ることができた。また、X線結晶構造解析やNMR測定から、C_6F_5基と電子供与性芳香環化合物との間に興味あるのスタッキング相互作用が観察され、今後こうした物理的性質を分子認識機能や自己集合化機能として新物質に応用する研究の基盤ができた。また、以上で合成された新規化合物を鍵物質として利用して、新しい機能性化合物が合成できると考えられ、引き続き研究を発展させたい。

    researchmap

  • 生体触媒の人為的制御による新規キラルシントンの効率的調製と光学活性医薬品の開発

    研究課題/領域番号:09555288  1997年 - 1999年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    酒井 貴志, 南井 正好, 依馬 正, 宇高 正徳

      詳細を見る

    配分額:8000000円 ( 直接経費:8000000円 )

    1.光学活性化合物の合成
    医農薬や液晶などの機能性化合物を合成する上で有用と期待される不斉合成中間体を設計・合成した。含窒素不飽和三員環アジリンを有する1級アルコールやペンタフルオロフェニル基を有するシアノヒドリン類、テトラフェニルポルフィリンを置換基として有する不斉2級アルコールを中心に研究した。これらの不斉化合物の光学活性体は、リパーゼやスブチリシンといった加水分解酵素を触媒とする速度論的光学分割やパン酵母或いはその還元酵素を用いた不斉還元によって合成した。概して、高いエナンチオ選択性で光学活性体を得ることができた。3-フェニル-2H-アジリン-2-メタノールからは高ジアステレオ選択的な付加反応により、4種類の立体異性体をつくり分けることに成功した。また、2-アシロキシ-2-(ペンタフルオロフェニル)アセトニトリルからは、数ステップで新規な1,2-ジオール及び1,2-アミノアルコール誘導体へ導くことができた。
    2.極低温下でのリパーゼ反応
    リパーゼを用いた速度論的光学分割におけるエナンチオ選択性の温度依存性を系統的に調査した。上で述べた不斉アルコールをはじめとして様々なアルコールを試した。30℃からー60℃付近の温度範囲で反応を行ったところ、温度を下げるにつれてエナンチオ選択性が向上した。lnEを1/Tに対してプロットすると、ほとんどの場合、30℃からー40℃までは直線関係が認められた。直線部分からは理論式によりΔΔH^<【double plus】>とΔΔS^<【double plus】>が算出でき、反応機構に関する知見も得られた。
    3.パン酵母またはその還元酵素を用いたカルボニル化合物の不斉還元
    パン酵母またはそこから単離精製した還元酵素を用いた不斉還元により、医農薬合成に有用と考えられる光学活性アルコールを合成した。一般にパン酵母を用いた場合よりも単離精製した還元酵素を用いた方がエナンチオ選択性は高く、後者の多くの場合で、光学的に純粋なアルコールが得られた。

    researchmap

  • 新規高歪みポルフィリンの合成とその反応性に関する研究

    研究課題/領域番号:08751009  1996年

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    依馬 正

      詳細を見る

    配分額:1000000円 ( 直接経費:1000000円 )

    二つのポルフィリンを共有結合で連結する際、嵩高いスペーサーを用いることによりポルフィリン環に歪みを誘導しようと試みた。分子内架橋化ユニットとしてはキシリレンやナフタレンを試したが、目的化合物は得られないか得られても収率が低く単離精製が困難であった。そこで架橋ユニットとしては嵩高くないトリメチレン鎖を選び(架橋化反応の収率62%)、その亜鉛錯体に対して種々の異なる鎖長のジアミンH_2N(CH_2)_nNH_2を取り込ませることにより歪みが誘導されるか検討することにした。鎖長はn=2〜7のものを試し、紫外可視吸収スペクトルによる滴定実験を行った。全ての場合において、1等量のジアミンを添加した時点で吸収変化は無くなり定量的に1:1の会合錯体が形成されることが分かった。どの場合も会合定数は>10^7と大きな値を示すことが明らかになった。このような強い結合は二つの配位結合が同時に働くことによるものと思われる。さらに円二色性(CD)スペクトルを測定したところ、ジアミンの鎖長に応じて不斉励起子相互作用に基づく分裂型のコットン効果の大きさが劇的に変化した。これは、非常に強い二重配位結合により二つのポルフィリン間の距離と配向が柔軟に変化したものと考えられる。現在、このコンフォメーション変化(inducedfit)がポルフィリン環の歪みを誘起しているか調査中である。
    合成した不斉ポルフィリン二量体の配座解析は、NMR,CDスペクトル及び分子力場計算によって行った。その結果、二つのポルフィリンは互いにほぼ並行でずれた配置(slipped cofacial orientation)をとっていることが示唆された。これは生体中で見られるクロロフィルの配列様式と似ており、そのような配置とエネルギー及び電子移動効率との関係を研究する上で興味深い系が構築されたといえる。

    researchmap

  • 生体触媒の機能開発による多官能性キラル分子の創製

    研究課題/領域番号:07455362  1995年 - 1997年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    宇高 正徳, 坪井 貞夫, 依馬 正, 酒井 貴志

      詳細を見る

    配分額:6500000円 ( 直接経費:6500000円 )

    1.多官能性キラル合成素子の高立体選択的合成
    パン酵母無細胞抽出液から4段階のクロマトグラフィーにより1-クロロ-2-ヘキサノンに還元活性を示す酵素を単離精製し、それを用いて種々の多官能性ケトンを還元したところ、高光学純度で還元生成物が得られた。
    リパーゼ触媒エステル交換反応により種々のキラル合成中間体の速度論的光学分割を行ったところ、高いエナンチオ選択性で分割できた。
    2.エナンチオ選択性の人為的向上
    1-クロロ-2,4-アルカンジオンのパン酵母還元において、偶然、微量の有機溶媒が特定の酵素を阻害し立体選択性を変化させることを見いだした。有機溶媒と阻害剤と熱処理を併用することにより、6%eeを94%eeまで向上できた。
    有機溶媒中におけるリパーゼ触媒エステル化反応においては、系中でアシル-酵素中間体が生成するので、アシル化試薬のアシル基の構造を変えれば中間体の構造も変化し、エナンチオ選択性が変化すると期待される。2-置換シクロペンテノールについて試したところ、E値が大きく変化した。
    リパーゼ触媒エステル交換反応を室温から-60℃の温度範囲で行ったところ、温度を下げるにつれてエナンチオ選択性が向上する事実を見いだした。このような極低温下での酵素反応は前例のない新規なものである。lnEを1/Tに対してプロットすると-40℃までは直線関係が得られた。直線部分からは理論式によりΔΔH^‡とΔΔS^‡を算出できた。
    3.エナンチオ選択性の発現機構
    種々のリパーゼの2級アルコールに対するアシル化反応を速度論的に解析した結果、基質結合段階における分子認識は重要ではなく、遷移状態において不斉識別が行われている事実を見い出した。遷移状態の性質を立体電子理論の立場から考察し、分子軌道計算を行った。リパーゼの結晶構造を用いた分子モデリングを行った。リパーゼのエナンチオ選択性の起源を説明できる「遷移状態モデル」を提唱した。

    researchmap

▼全件表示

 

担当授業科目

  • 先端分子デザイン概論2 (2023年度) 夏季集中  - その他

  • 化学・生命系英語1 (2023年度) 第1学期  - 水3~4

  • 化学・生命系英語2 (2023年度) 第2学期  - 水3~4

  • 化学生命系概論 (2023年度) 第1学期  - その他

  • 化学生命系英語1 (2023年度) 第1学期  - 水3~4

  • 化学生命系英語2 (2023年度) 第2学期  - 水3~4

  • 合成化学各論2 (2023年度) 夏季集中  - その他

  • 合成有機化学演習 (2023年度) その他  - その他

  • 合成有機化学演習 (2023年度) 通年  - その他

  • 合成有機化学特別演習 (2023年度) 通年  - その他

  • 基礎有機化学 (2023年度) 第1学期  - 金3~4

  • 外国書講読A (2023年度) 第1学期  - 水3~4

  • 外国書講読B (2023年度) 第2学期  - 水3~4

  • 実用分子設計 (2023年度) 後期  - 木1~2

  • 工業概論 (2023年度) 3・4学期  - 木1~2

  • 工業概論 (2023年度) 3・4学期  - [第3学期]木1~2, [第4学期]その他

  • 工業概論 (2023年度) 3・4学期  - 木1~2

  • 応用化学ゼミナール1 (2023年度) 前期  - その他

  • 応用化学ゼミナール2 (2023年度) 後期  - その他

  • 応用化学特別研究 (2023年度) 通年  - その他

  • 応用化学系演習 (2023年度) その他  - その他

  • 日英実践技術表現法 (2023年度) 通年  - 金3~4

  • 日英実践技術表現法 (2023年度) 通年  - [前期]金3~4, [後期]その他

  • 有機化学1A (2023年度) 第1学期  - 月1~2

  • 有機化学1B (2023年度) 第1学期  - 木3~4

  • 有機化学Ⅱ (2023年度) 第1学期  - 月1,木3

  • 有機化学Ⅲ (2023年度) 第1学期  - 月2,木4

  • 有機化学基礎1 (2023年度) 第1学期  - 金3~4

  • 有機化学基礎2 (2023年度) 第2学期  - 金3~4

  • 有機化学1 (2023年度) 1・2学期  - 金3~4

  • 有機化学2 (2023年度) 第1学期  - 月1~2,木3~4

  • 有機化学I (2023年度) 第2学期  - 金3~4

  • 機能性分子合成論 (2023年度) 後期  - その他

  • 機能性分子合成論 (2023年度) 後期  - その他

  • 物質合成化学特論2 (2023年度) 夏季集中  - その他

  • 特別研究 (2023年度) その他  - その他

  • 生体関連有機化学 (2023年度) 後期  - その他

  • 生物有機化学 (2023年度) 後期  - その他

  • 立体化学 (2023年度) 第4学期  - 金3~4

  • 化学生命系概論 (2022年度) 第1学期  - その他

  • 化学生命系英語 (2022年度) 1・2学期  - 水3~4

  • 化学生命系英語1 (2022年度) 第1学期  - 水3~4

  • 化学生命系英語2 (2022年度) 第2学期  - 水3~4

  • 合成化学各論2 (2022年度) 夏季集中  - その他

  • 合成化学各論4 (2022年度) 夏季集中  - その他

  • 合成化学各論1 (2022年度) 第1学期  - 金3~4

  • 合成化学各論2 (2022年度) 第2学期  - 金3~4

  • 合成有機化学演習 (2022年度) 通年  - その他

  • 基礎有機化学 (2022年度) 第1学期  - 金3~4

  • 実践応用化学 (2022年度) 前期  - その他

  • 専門英語 (2022年度) 3・4学期  - 木3~4

  • 専門英語1 (2022年度) 第3学期  - 木3~4

  • 専門英語2 (2022年度) 第4学期  - 木3~4

  • 工業概論 (2022年度) 3・4学期  - 木1~2

  • 工業概論 (2022年度) 3・4学期  - 木1~2

  • 応用化学ゼミナール1 (2022年度) 前期  - その他

  • 応用化学ゼミナール2 (2022年度) 後期  - その他

  • 応用化学基礎 (2022年度) 後期  - 月3~4,火3~4

  • 応用化学特別研究 (2022年度) 通年  - その他

  • 日英実践技術表現法 (2022年度) 前期  - 金3,金4

  • 有機化学1A (2022年度) 第1学期  - 月1~2

  • 有機化学1B (2022年度) 第1学期  - 木3~4

  • 有機化学Ⅱ (2022年度) 第1学期  - 月1,木3

  • 有機化学Ⅲ (2022年度) 第1学期  - 月2,木4

  • 有機化学及び演習1 (2022年度) 第1学期  - 月1~2,木3~4

  • 有機化学基礎 (2022年度) 1・2学期  - 金3~4

  • 有機化学基礎1 (2022年度) 第1学期  - 金3~4

  • 有機化学基礎2 (2022年度) 第2学期  - 金3~4

  • 有機化学1 (2022年度) 第1学期  - 月1~2,木3~4

  • 有機化学1 (2022年度) 1・2学期  - 金3~4

  • 有機化学2 (2022年度) 第1学期  - 月1~2,木3~4

  • 有機化学I (2022年度) 第2学期  - 金3~4

  • 機能分子化学 (2022年度) 第2学期  - 木5~7

  • 機能分子化学 (2022年度) 第2学期  - 木5~7

  • 機能性分子合成論 (2022年度) 後期  - その他

  • 物質合成化学特論6 (2022年度) 夏季集中  - その他

  • 生体関連有機化学 (2022年度) 後期  - 木1,木2

  • 立体化学 (2022年度) 第4学期  - 火3~4

  • 立体化学 (2022年度) 第4学期  - 火3~4

▼全件表示