Updated on 2025/06/06

写真a

 
SAKAKURA Akira
 
Organization
Faculty of Environmental, Life, Natural Science and Technology Professor
Position
Professor
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Degree

  • 学術 ( 2000.10   名古屋大学 )

Research Interests

  • 生物有機化学

  • 有機合成化学

Research Areas

  • Nanotechnology/Materials / Chemistry and chemical methodology of biomolecules

  • Nanotechnology/Materials / Synthetic organic chemistry

Education

  • Nagoya University   大学院人間情報学研究科  

    1995.4 - 2000.6

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    Country: Japan

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  • Nagoya University   大学院理学研究科   化学専攻

    1993.4 - 1995.3

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    Country: Japan

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  • Nagoya University   理学部   化学科

    1989.4 - 1993.3

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    Country: Japan

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Research History

  • Okayama University   Graduate School of Natural Science and Technology   Professor

    2012.9

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  • Nagoya University   EcoTopia Science Institute   Associate Professor

    2007.4 - 2012.8

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  • Nagoya University   Graduate School of Engineering   Associate Professor

    2003.3 - 2007.3

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  • University of Tsukuba   Department of Chemistry   Assistant Professor

    2001.4 - 2003.2

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Professional Memberships

Committee Memberships

  • 日本化学会中国四国支部   岡山地区幹事  

    2015.4 - 2017.3   

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    Committee type:Academic society

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  • 有機合成化学協会中国四国支部   事務局  

    2013.4   

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    Committee type:Academic society

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  • 日本化学会東海支部   代表正会員  

    2011.4 - 2013.3   

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    Committee type:Academic society

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Papers

  • Rapid construction of a diterpene-inspired tetracyclic skeleton bearing bicyclo[3.2.1]octane rings based on desymmetrization of 1,3-diketones

    Hidetoshi Kamada, Haruki Mizoguchi, Akira Sakakura

    Tetrahedron Letters   2025.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.tetlet.2025.155470

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  • Synthesis and biological evaluation of coprinoferrin, an acylated tripeptide hydroxamate siderophore

    Ichiro Hayakawa, Tomoki Isogai, Jun Takanishi, Shihori Asai, Chika Ando, Tomohiro Tsutsumi, Kenji Watanabe, Akira Sakakura, Yuta Tsunematsu

    Organic & Biomolecular Chemistry   2024

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    Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry (RSC)  

    Coprinoferrin (CPF), originally isolated from a genetically engineered strain (∆laeA) of mushroom fungus Coprinopsis cinerea, is an acylated tripeptide hydroxamate consisting of tandem aligned N5-hexanoyl-N5-hydroxy-L-ornithine with modifications of N-acetyl and...

    DOI: 10.1039/d3ob01850d

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  • Visible-Light-Photoexcited Palladium-Catalyzed Silylmethylation of Benzyl Alcohol Derivatives Invited Reviewed

    Haruki Mizoguchi, Akira Sakakura, Ryuji Yoshida, Haruka Ikeda

    Synlett   34 ( 20 )   2451 - 2454   2023.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1055/s-0042-1752736

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  • Enantioselective construction of beta-hydroxy-alpha,alpha-disubstituted alpha-amino acid derivatives via direct aldol reaction of alpha-imino esters Reviewed

    Yuya Araki, Masato Hanada, Yoshiko Iguchi, Haruki Mizoguchi, Akira Sakakura

    TETRAHEDRON   110   2022.3

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.tet.2022.132695

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  • Annulative coupling of vinylboronic esters: aryne-triggered 1,2-metallate rearrangement Reviewed

    Haruki Mizoguchi, Hidetoshi Kamada, Kazuki Morimoto, Ryuji Yoshida, Akira Sakakura

    Chemical Science   13 ( 33 )   9580 - 9585   2022

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1039/D2SC02623F

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  • Toward the Synthesis of Paspaline-Type Indole-Terpenes: Stereoselective Construction of Core Scaffold with Contiguous Asymmetric Quaternary Carbon Centers Reviewed

    Ichiro Hayakawa, Naochika Matsumaru, Akira Sakakura

    The Journal of Organic Chemistry   86 ( 14 )   9802 - 9810   2021.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society ({ACS})  

    DOI: 10.1021/acs.joc.1c01193

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  • Strain-release Difunctionalization of C–C σ- and π-bonds of an Organoboron Ate-complex through 1,2-Metallate Rearrangement Invited Reviewed

    Haruki Mizoguchi, Akira Sakakura

    Chemistry Letters   50 ( 4 )   792 - 799   2021.4

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Chemical Society of Japan  

    DOI: 10.1246/cl.200926

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  • Dual Inhibition of γ-Tubulin and Plk1 Induces Mitotic Cell Death Reviewed

    Haruna Ebisu, Kana Shintani, Takumi Chinen, Yoko Nagumo, Shuya Shioda, Taisei Hatanaka, Akira Sakakura, Ichiro Hayakawa, Hideo Kigoshi, Takeo Usui

    Frontiers in Pharmacology   11   2021.1

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    α/β-Tubulin inhibitors that alter microtubule (MT) dynamics are commonly used in cancer therapy, however, these inhibitors also cause severe side effects such as peripheral neuropathy. γ-Tubulin is a possible target as antitumor drugs with low side effects, but the antitumor effect of γ-tubulin inhibitors has not been reported yet. In this study, we verified the antitumor activity of gatastatin, a γ-tubulin specific inhibitor. The cytotoxicity of gatastatin was relatively weak compared with that of the conventional MT inhibitors, paclitaxel and vinblastine. To improve the cytotoxicity, we screened the chemicals that improve the effects of gatastatin and found that BI 2536, a Plk1 inhibitor, greatly increases the cytotoxicity of gatastatin. Co-treatment with gatastatin and BI 2536 arrested cell cycle progression at mitosis with abnormal spindles. Moreover, mitotic cell death induced by the combined treatment was suppressed by the Mps1 inhibitor, reversine. These findings suggest that co-treatment with Plk1 and γ-tubulin inhibitors causes spindle assembly checkpoint-dependent mitotic cell death by impairing centrosome functions. These results raise the possibility of Plk1 and γ-tubulin inhibitor co-treatment as a novel cancer chemotherapy.

    DOI: 10.3389/fphar.2020.620185

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  • Kinetic Resolution of α-Nitrolactones by Catalytic Asymmetric Hydrolysis or Ester–Amide Exchange Reaction Reviewed

    Akira Sakakura, Ryota Nakao, Yudai Fujii, Ichiro Hayakawa, Haruki Mizoguchi

    Synlett   31 ( 20 )   2018 - 2022   2020.12

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Georg Thieme Verlag {KG}  

    <title>Abstract</title>
    C
    1-Symmetric chiral ammonium salt catalysts induced a kinetic resolution of racemic α-nitrolactones through an asymmetric ester–amide exchange reaction. The corresponding amides were obtained with high enantioselectivities and high S (= k
    fast/k
    slow) values. This reaction system is a useful approach for obtaining carbocyclic quaternary α-nitroamides as chiral building blocks.

    DOI: 10.1055/s-0040-1707303

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  • Enantioselective Diels–Alder Reaction of 3-Nitrocoumarins Promoted by Chiral Organoammonium Salt Catalysts Reviewed

    Akira Sakakura, Yudai Fujii, Ryota Nakao, Saki Sugihara, Keita Fujita, Yuya Araki, Takayuki Kudoh, Ichiro Hayakawa, Haruki Mizoguchi

    Synlett   31 ( 20 )   2013 - 2017   2020.12

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    <title>Abstract</title>An enantioselective Diels–Alder reaction of 3-nitrocoumarins has been developed. A tryptophan-derived C
    1-symmetric organoammonium thiourea catalyst promoted the reaction of 3-nitrocoumarins with Danishefsky’s diene to give the corresponding adducts with good enantioselectivity (up to 94% ee). One of the resulting adducts was converted into a chiral carbocyclic quaternary β-amino alcohol.

    DOI: 10.1055/s-0040-1707302

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  • Structure Optimization of Gatastatin for the Development of gamma-Tubulin-Specific Inhibitor Reviewed

    Kana Shintani, Haruna Ebisu, Minagi Mukaiyama, Taisei Hatanaka, Takumi Chinen, Daisuke Takao, Yoko Nagumo, Akira Sakakura, Ichiro Hayakawa, Takeo Usui

    ACS MEDICINAL CHEMISTRY LETTERS   11 ( 6 )   1125 - 1129   2020.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/acsmedchemlett.9b00526

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  • Formal Total Synthesis of Manzacidin B via Sequential Diastereodivergent Henry Reaction Reviewed

    Yuya Araki, Natsumi Miyoshi, Kazuki Morimoto, Takayuki Kudoh, Haruki Mizoguchi, Akira Sakakura

    JOURNAL OF ORGANIC CHEMISTRY   85 ( 2 )   798 - 805   2020.1

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    DOI: 10.1021/acs.joc.9b02811

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  • Synthesis of functionalized cyclopropylboronic esters based on a 1,2-metallate rearrangement of cyclopropenylboronate Reviewed

    Haruki Mizoguchi, Masaya Seriu, Akira Sakakura

    Chemical Communications   56 ( 99 )   15545 - 15548   2020

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    DOI: 10.1039/d0cc07134j

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  • Toward the Synthesis of SB-203207: Construction of Four Contiguous Nitrogen-Containing Stereogenic Centers Reviewed

    Ichiro Hayakawa, Anna Nagayasu, Akira Sakakura

    The Journal of Organic Chemistry   84 ( 23 )   15614 - 15623   2019.12

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    DOI: 10.1021/acs.joc.9b02627

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  • Enantioselective 1,3-Dipolar Cycloaddition Reaction of Nitrones with α-(Acyloxy)acroleins Catalyzed by Dipeptide-Derived Chiral Tri- or Diammonium Salts Reviewed

    Chihiro Kidou, Haruki Mizoguchi, Tatsuo Nehira, Akira Sakakura

    Synlett   30 ( 15 )   1835 - 1839   2019.9

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    DOI: 10.1055/s-0039-1690133

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  • Toward the Synthesis of Yuzurimine-Type Alkaloids: Stereoselective Construction of the Heterocyclic Portions of Deoxyyuzurimine and Macrodaphnine Reviewed International journal

    Ichiro Hayakawa, Ryosuke Nagatani, Masaki Ikeda, Dong-eun Yoo, Keita Saito, Hideo Kigoshi, Akira Sakakura

    Organic Letters   21 ( 16 )   6337 - 6341   2019.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/acs.orglett.9b02232

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  • Thioureas as Highly Active Catalysts for Biomimetic Bromocyclization of Geranyl Derivatives Reviewed

    Miyuki Terazaki, Kei-ichi Shiomoto, Haruki Mizoguchi, Akira Sakakura

    Organic Letters   21 ( 7 )   2073 - 2076   2019.4

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    DOI: 10.1021/acs.orglett.9b00352

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  • Catalytic enantioselective Hosomi–Sakurai reaction of α-ketoesters promoted by chiral copper(ii) complexes Reviewed

    Yutaro Niwa, Mayu Miyake, Ichiro Hayakawa, Akira Sakakura

    Chemical Communications   55 ( 27 )   3923 - 3926   2019

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    DOI: 10.1039/C9CC01159E

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  • Chiral Pyrophosphoric Acid Catalysts for the para-Selective and Enantioselective Aza-Friedel–Crafts Reaction of Phenols Reviewed

    Akira Sakakura, Manabu Hatano, Kazuaki Ishihara, Haruka Okamoto, Kohei Toh, Takuya Mochizuki, Hidefumi Nakatsuji

    Synthesis   50 ( 23 )   4577 - 4590   2018.12

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1055/s-0037-1610250

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  • Enantioselective aza-Friedel–Crafts reaction of furan with α-ketimino esters induced by a conjugated double hydrogen bond network of chiral bis(phosphoric acid) catalysts Reviewed

    Manabu Hatano, Haruka Okamoto, Taro Kawakami, Kohei Toh, Hidefumi Nakatsuji, Akira Sakakura, Kazuaki Ishihara

    Chemical Science   9 ( 30 )   6361 - 6367   2018

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    DOI: 10.1039/C8SC02290A

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  • REGIOSELECTIVE DMAD-INSERTION REACTION OF SILYL DIENOL ETHER OF gamma-PYRONE UNDER CATALYST- AND HEATING-FREE CONDITIONS Reviewed

    Ichiro Hayakawa, Yuji Yamanaka, Koichi Mitsudo, Hiromi Ota, Akira Sakakura

    HETEROCYCLES   94 ( 12 )   2299 - 2306   2017.12

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    DOI: 10.3987/COM-17-13820

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  • Diastereodivergent Henry Reaction for the Stereoselective Construction of Nitrogen-Containing Tetrasubstituted Carbons: Application to Total Synthesis of Manzacidins A and C Reviewed

    Takayuki Kudoh, Yuya Araki, Natsumi Miyoshi, Mizuho Tanioka, Akira Sakakura

    ASIAN JOURNAL OF ORGANIC CHEMISTRY   6 ( 12 )   1760 - 1763   2017.12

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    DOI: 10.1002/ajoc.201700568

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  • Heat Versus Basic Conditions: Intramolecular Dehydro-Diels-Alder Reaction of 1-Indolyl-1,6-heptadiynes for the Selective Synthesis of Substituted Carbazoles Reviewed

    Takayuki Kudoh, Syo Fujisawa, Megumi Kitamura, Akira Sakakura

    SYNLETT   28 ( 16 )   2189 - 2193   2017.10

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    DOI: 10.1055/s-0036-1588461

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  • Reinvestigation of the Biomimetic Cyclization of 3,5-Diketo Esters: Application to the Total Synthesis of Cyercene A, an alpha-Methoxy-gamma-Pyrone-Containing Polypropionate Reviewed

    Kai Onda, Ichiro Hayakawa, Akira Sakakura

    SYNLETT   28 ( 13 )   1596 - 1600   2017.8

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    DOI: 10.1055/s-0036-1588795

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  • Discovery of O-6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of alpha,beta-tubulin polymerization Reviewed

    Ichiro Hayakawa, Shuya Shioda, Takumi Chinen, Taisei Hatanaka, Haruna Ebisu, Akira Sakakura, Takeo Usui, Hideo Kigoshi

    BIOORGANIC & MEDICINAL CHEMISTRY   24 ( 21 )   5639 - 5645   2016.11

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    DOI: 10.1016/j.bmc.2016.09.026

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  • A short access to 3,5-disubstituted piperazinones based on the aza-Michael addition of alpha-amino esters to beta-substituted nitroalkenes Reviewed

    Takayuki Kudoh, Seiji Isoyama, Sachiko Kagimoto, Katsutoshi Kurihara, Akira Sakakura

    TETRAHEDRON LETTERS   57 ( 42 )   4693 - 4696   2016.10

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    DOI: 10.1016/j.tetlet.2016.09.015

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  • Enantioselective bromocyclization of 2-geranylphenols induced by chiral phosphite-urea bifunctional catalysts Reviewed

    Yasuhiro Sawamura, Yoshihiro Ogura, Hidefumi Nakatsuji, Akira Sakakura, Kazuaki Ishihara

    CHEMICAL COMMUNICATIONS   52 ( 36 )   6068 - 6071   2016

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1039/c6cc00229c

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  • Stereoselective Electrophilic Cyclization Reviewed

    Akira Sakakura, Kazuaki Ishihara

    CHEMICAL RECORD   15 ( 4 )   728 - 742   2015.8

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    DOI: 10.1002/tcr.201500005

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  • Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Imines with Propioloylpyrazoles Induced by Chiral pi-Cation Catalysts Reviewed

    Masahiro Hori, Akira Sakakura, Kazuaki Ishihara

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   136 ( 38 )   13198 - 13201   2014.9

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/ja508441t

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  • Selective Bromocyclization of 2-Geranylphenols Promoted by Phosphite-Urea Cooperative Catalysts Reviewed

    Yasuhiro Sawamura, Hidefumi Nakatsuji, Matsujiro Akakura, Akira Sakakura, Kazuaki Ishihara

    CHIRALITY   26 ( 7 )   356 - 360   2014.7

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    DOI: 10.1002/chir.22297

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  • Cooperative Activation with Chiral Nucleophilic Catalysts and N-Haloimides: Enantioselective Iodolactonization of 4-Arylmethyl-4-pentenoic Acids Reviewed

    Hidefumi Nakatsuji, Yasuhiro Sawamura, Akira Sakakura, Kazuaki Ishihara

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   53 ( 27 )   6974 - 6977   2014.7

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/anie.201400946

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  • Catalytic Enantioselective Inverse Electron Demand Hetero-Diels-Alder Reaction with Allylsilanes Reviewed

    Yuki Matsumura, Takahiro Suzuki, Akira Sakakura, Kazuaki Ishihara

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   53 ( 24 )   6131 - 6134   2014.6

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    DOI: 10.1002/anie.201402934

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  • Enantioselective Cyanoethoxycarbonylation of Isatins Promoted by a Lewis Base-Bronsted Acid Cooperative Catalyst Reviewed

    Yoshihiro Ogura, Matsujiro Akakura, Akira Sakakura, Kazuaki Ishihara

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   52 ( 32 )   8299 - 8303   2013.8

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    DOI: 10.1002/anie.201303572

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  • Primary Alkylboronic Acids as Highly Active Catalysts for the Dehydrative Amide Condensation of alpha-Hydroxycarboxylic Acids Reviewed

    Risa Yamashita, Akira Sakakura, Kazuaki Ishihara

    ORGANIC LETTERS   15 ( 14 )   3654 - 3657   2013.7

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/ol401537f

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  • Kinetic Resolution of Racemic Carboxylic Acids through Asymmetric Protolactonization Promoted by Chiral Phosphonous Acid Diester Reviewed

    Masayuki Sakuma, Akira Sakakura, Kazuaki Ishihara

    ORGANIC LETTERS   15 ( 11 )   2838 - 2841   2013.6

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    DOI: 10.1021/ol401313d

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  • "Phosphite-urea" cooperative high-turnover catalysts for the highly selective bromocyclization of homogeranylarenes Reviewed

    Yasuhiro Sawamura, Hidefumi Nakatsuji, Akira Sakakura, Kazuaki Ishihara

    CHEMICAL SCIENCE   4 ( 11 )   4181 - 4186   2013

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1039/c3sc51432c

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  • alpha-Heterosubstituted beta-Alkylacroleins as Useful Multisubstituted Dienophiles for Enantioselective Diels-Alder Reactions Reviewed

    Akira Sakakura, Hiroki Yamada, Kazuaki Ishihara

    ASIAN JOURNAL OF ORGANIC CHEMISTRY   1 ( 2 )   133 - 137   2012.10

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ajoc.201200054

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  • Enantioselective Diels-Alder Reaction of alpha-(Acylthio)acroleins: A New Entry to Sulfur-Containing Chiral Quaternary Carbons Reviewed

    Akira Sakakura, Hiroki Yamada, Kazuaki Ishihara

    ORGANIC LETTERS   14 ( 12 )   2972 - 2975   2012.6

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    DOI: 10.1021/ol300921f

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  • N,N-Diarylammonium Pyrosulfate as a Highly Effective Reverse Micelle-Type Catalyst for Hydrolysis of Esters Reviewed

    Yoshiki Koshikari, Akira Sakakura, Kazuaki Ishihara

    ORGANIC LETTERS   14 ( 12 )   3194 - 3197   2012.6

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    DOI: 10.1021/ol301290c

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  • Hydrophobic N,N-Diarylammonium Pyrosulfates as Dehydrative Condensation Catalysts under Aqueous Conditions Reviewed

    Akira Sakakura, Yoshiki Koshikari, Matsujiro Akakura, Kazuaki Ishihara

    ORGANIC LETTERS   14 ( 1 )   30 - 33   2012.1

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    DOI: 10.1021/ol2027366

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  • Aplyronines D-H from the sea hare Aplysia kurodai: isolation, structures, and cytotoxicity Reviewed

    Makoto Ojika, Hideo Kigoshi, Kiyotake Suenaga, Yoshifumi Imamura, Kohji Yoshikawa, Takeshi Ishigaki, Akira Sakakura, Tsuyoshi Mutou, Kiyoyuki Yamada

    TETRAHEDRON   68 ( 4 )   982 - 987   2012.1

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    DOI: 10.1016/j.tet.2011.11.095

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  • Desymmetrization of meso-Glycerol Derivatives Induced by L-Histidine-Derived Acylation Catalysts Reviewed

    Akira Sakakura, Shuhei Umemura, Kazuaki Ishihara

    ADVANCED SYNTHESIS & CATALYSIS   353 ( 11-12 )   1938 - 1942   2011.8

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/adsc.201100252

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  • Chiral Lewis Base-Assisted Brønsted Acid (LBBA)-Catalyzed Enantioselective Cyclization of 2-Geranylphenols Reviewed

    Akira Sakakura, Masayuki Sakuma, Kazuaki Ishihara

    ORGANIC LETTERS   13 ( 12 )   3130 - 3133   2011.6

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    DOI: 10.1021/ol201032t

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  • Bronsted Base-Assisted Boronic Acid Catalysis for the Dehydrative Intramolecular Condensation of Dicarboxylic Acids Reviewed

    Akira Sakakura, Takuro Ohkubo, Risa Yamashita, Matsujiro Akakura, Kazuaki Ishihara

    ORGANIC LETTERS   13 ( 5 )   892 - 895   2011.3

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    DOI: 10.1021/ol102926n

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  • Intramolecular Dehydrative Condensation of Dicarboxylic Acids with Bronsted Base-Assisted Boronic Acid Catalysts Reviewed

    Akira Sakakura, Risa Yamashita, Takuro Ohkubo, Matsujiro Akakura, Kazuaki Ishihara

    AUSTRALIAN JOURNAL OF CHEMISTRY   64 ( 11 )   1458 - 1465   2011

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1071/CH11301

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  • Asymmetric Cu(II) catalyses for cycloaddition reactions based on pi-cation or pi-cation interactions Reviewed

    Akira Sakakura, Kazuaki Ishihara

    CHEMICAL SOCIETY REVIEWS   40 ( 1 )   163 - 172   2011

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    Authorship:Lead author   Language:English  

    DOI: 10.1039/b924478f

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  • NUCLEOPHILIC PHOSPHINE-CATALYZED IODOCYCLIZATION OF ISOPRENOIDS BEARING AN OXYGEN TERMINAL GROUP Reviewed

    Akira Sakakura, Gakujun Shomi, Atsushi Ukai, Kazuaki Ishihara

    HETEROCYCLES   82 ( 1 )   249 - 255   2010.12

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3987/COM-09-S(E)1

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  • Catalytic Enantioselective 1,3-Dipolar Cycloadditions of Nitrones with Propioloylpyrazoles and Acryloylpyrazoles Induced by Chiral pi-Cation Catalysts Reviewed

    Akira Sakakura, Masahiro Hori, Makoto Fushimi, Kazuaki Ishihara

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   132 ( 44 )   15550 - 15552   2010.11

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    DOI: 10.1021/ja1081603

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  • ChemInform Abstract: Jolkinolide D Pharmacophore: Synthesis and Reaction with Amino Acids, Nucleosides, and DNA.

    Akira Sakakura, Yui Takayanagi, Hideo Kigoshi

    ChemInform   33 ( 46 )   no - no   2010.5

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    DOI: 10.1002/chin.200246184

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  • Organoammonium Salt-Catalyzed Enantioselective Cycloaddition Reactions with alpha-(Acyloxy)- or alpha-Diacylaminoacroleins Reviewed

    Akira Sakakura, Kazuaki Ishihara

    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN   83 ( 4 )   313 - 322   2010.4

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    DOI: 10.1246/bcsj.20090345

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  • Rational Design of Highly Effective Asymmetric Diels-Alder Catalysts Bearing 4,4 '-Sulfonamidomethyl Groups Reviewed

    Akira Sakakura, Rei Kondo, Yuki Matsumura, Matsujiro Akakura, Kazuaki Ishihara

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   131 ( 49 )   17762 - 17764   2009.12

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    DOI: 10.1021/ja906098b

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  • 3-Pyrroline-1-carbonyl (Pyroc) Group: A Removable Protecting Group for the Kinetic Resolution of Racemic Carboxylic Acids and Alcohols through Catalytic Asymmetric Acylation Reviewed

    Akira Sakakura, Shuhei Umemura, Kazuaki Ishihara

    SYNLETT   ( 10 )   1647 - 1650   2009.6

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    DOI: 10.1055/s-0029-1217321

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  • Dehydrative cyclization of serine, threonine, and cysteine residues catalyzed by molybdenum(VI) oxo compounds Reviewed

    Akira Sakakura, Rei Kondo, Shuhei Umemura, Kazuaki Ishihara

    TETRAHEDRON   65 ( 10 )   2102 - 2109   2009.3

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    DOI: 10.1016/j.tet.2008.12.074

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  • Design of High-Performance Catalysts Based on Acid-Base Combined Salts and Development of Highly Selective Reactions Reviewed

    Akira Sakakura

    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN   66 ( 10 )   942 - 952   2008.10

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    DOI: 10.5059/yukigoseikyokaishi.66.942

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  • SELECTIVE SYNTHESIS OF CYCLIC PHOSPHORIC ACID DIESTERS THROUGH OXORHENIUM(VII)-CATALYZED DEHYDRATIVE CONDENSATION OF PHOSPHORIC ACID WITH ALCOHOLS Reviewed

    Akira Sakakura, Masayuki Sakuma, Mikimoto Katsukawa, Kazuaki Ishihara

    HETEROCYCLES   76 ( 1 )   657 - 665   2008.9

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  • Kinetic resolution of racemic carboxylic acids by an L-histidine-derived sulfonamide-induced enantioselective esterification reaction Reviewed

    Kazuaki Ishihara, Yuji Kosugi, Shuhei Umemura, Akira Sakakura

    ORGANIC LETTERS   10 ( 15 )   3191 - 3194   2008.8

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    DOI: 10.1021/ol801007m

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  • Open-air and solvent-free ester condensation catalyzed by sulfonic acids Reviewed

    Akira Sakakura, Yoshiki Koshikari, Kazuaki Ishihara

    TETRAHEDRON LETTERS   49 ( 34 )   5017 - 5020   2008.8

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    DOI: 10.1016/j.tetlet.2008.06.058

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  • Rate-accelerating effect by the neighboring-group participation of protecting groups in the dehydrative cyclization of 1,3,5-triketones Reviewed

    Akira Sakakura, Hitoshi Watanabe, Kazuaki Ishihara

    ORGANIC LETTERS   10 ( 12 )   2569 - 2572   2008.6

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    DOI: 10.1021/ol800860p

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  • Convergent total syntheses of fluvibactin and vibriobactin using molybdenum(VI) oxide-catalyzed dehydrative cyclization as a key step Reviewed

    Akira Sakakura, Shuhei Umemura, Kazuaki Ishihara

    CHEMICAL COMMUNICATIONS   ( 30 )   3561 - 3563   2008

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    DOI: 10.1039/b805880f

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  • Widely useful DMAP-catalyzed esterification under auxiliary base- and solvent-free conditions Reviewed

    Akira Sakakura, Kirnio Kawajiri, Takuro Ohkubo, Yuji Kosugi, Kazuaki Ishihara

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   129 ( 47 )   14775 - 14779   2007.11

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    DOI: 10.1021/ja075824w

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  • Enantioselective biomimetic polyene cyclization of polyprenoids - Long-sought enantioselective reaction induced by a "chiral halonium ion" Reviewed

    Akira Sakakura, Kazuaki Ishihara

    CHIMICA OGGI-CHEMISTRY TODAY   25 ( 5 )   9 - 12   2007.9

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  • Catalytic synthesis of peptide-derived thiazolines and oxazolines using Bis(quinolinolato)dioxomolybdenum(VI) complexes Reviewed

    Akira Sakakura, Rei Kondo, Shuhei Umemura, Kazuaki Ishihara

    ADVANCED SYNTHESIS & CATALYSIS   349 ( 10 )   1641 - 1646   2007.7

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    DOI: 10.1002/adsc.200700068

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  • Dehydrative cyclization catalyzed by the combination of molybdenum(VI) oxides and benzoic acids: First synthesis of the antitumour substance BE-70016 Reviewed

    Akira Sakakura, Shuhei Umemura, Rei Kondo, Kazuaki Ishihara

    ADVANCED SYNTHESIS & CATALYSIS   349 ( 4-5 )   551 - 555   2007.3

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    DOI: 10.1002/adsc.200600550

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  • Design of highly functional small-molecule catalysts and related reactions based on acid-base combination chemistry Reviewed

    Kazuaki Ishihara, Akira Sakakura, Manabu Hatano

    SYNLETT   ( 5 )   686 - 703   2007.3

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    DOI: 10.1055/s-2007-970776

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  • Enantioselective halocyclization of polyprenoids induced by nucleophilic phosphoramidites Reviewed

    Akira Sakakura, Atsushi Ukai, Kazuaki Ishihara

    NATURE   445 ( 7130 )   900 - 903   2007.2

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    DOI: 10.1038/nature05553

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  • Unusual rate acceleration in bronsted acid catalyzed dehydration reactions: Local hydrophobic environment in aggregated N-(2,6-diphenylphenyl)-N-mesitylammonium pentafluorobenzenesulfonates Reviewed

    Akira Sakakura, Hitoshi Watanabe, Shoko Nakagawa, Kazuaki Ishihara

    CHEMISTRY-AN ASIAN JOURNAL   2 ( 4 )   477 - 483   2007

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    DOI: 10.1002/asia.200600380

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  • Direct ester condensation catalyzed by bulky diarylammonium pentafluorobenzenesulfonates Reviewed

    Akira Sakakura, Shoko Nakagawa, Kazuaki Ishihara

    NATURE PROTOCOLS   2 ( 7 )   1746 - 1751   2007

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    DOI: 10.1038/nprot.2007.254

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  • Bulky phosphazenium cation catalysis for dehydrative condensation of phosphoric acid with alcohols Reviewed

    Akira Sakakura, Mikimoto Katsukawa, Takaomi Hayashi, Kazuaki Ishihara

    GREEN CHEMISTRY   9 ( 11 )   1166 - 1169   2007

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    DOI: 10.1039/b707974e

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  • The oxorhenium(VII)-catalyzed direct condensation of phosphoric acid with an alcohol Reviewed

    Akira Sakakura, Mikimoto Katsukawa, Kazuaki Ishihara

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   46 ( 9 )   1423 - 1426   2007

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    DOI: 10.1002/anie.200604333

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  • Enantioselective Diels-Alder reaction of alpha-acyloxyacroleins catalyzed by chiral 1,1 '-binaphthyl-2,2 '-diammonium salts Reviewed

    Akira Sakakura, Kenji Suzuki, Kazuaki Ishihara

    ADVANCED SYNTHESIS & CATALYSIS   348 ( 16-17 )   2457 - 2465   2006.11

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    DOI: 10.1002/adsc.200600322

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  • 35 Synthesis of Aurisides A and B, Cytotoxic Macrolide Glycosides of Marine Origin

    Suenaga Kiyotake, Hoshino Hiroshi, Yoshii Takanori, Mori Kazunori, Sone Hiroki, Bessho Yuhki, Sakakura Akira, Hayakawa Ichiro, Yamada Kiyoyuki, Kigoshi Hideo

    Symposium on the Chemistry of Natural Products, symposium papers   ( 48 )   205 - 210   2006.9

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    Aurisides A (1) and B (2) are macrolide glycosides isolated from Japanese sea hare Dolabella auricuralia, which exhibit cytotoxicity against HeLa S_3 cells with IC_<50> values of 0.17 and 1.2μg/mL, respectively. The main structural features of aurisides are a bromine-substituted conjugated diene, a 14-membered lactone, and a cyclic hemiacetal. We achieved the enantioselective synthesis of aurisides A and B by a convergent approach. The C1-C9 segment 4 was prepared from (R)-pantolactone using a reaction of dithiane carbanion with epoxide, stereoselective reduction of β-hydroxyketone with Me_4NBHOAc, and rhodium-catalyzed Reformatsky-type reaction as key steps. The C10-C17 segment 12 was synthesized from (R)-glycidyl trityl ether. The Nozaki-Hiyama-Kishi reaction between 4 and 12 and subsequent reactions including construction of bromine-substituted conjugated diene gave seco acid 10, which was converted into the aglycon (3) of aurisides by construction of the 14-membered lactone. The Mukaiyama glycosylation reaction of the aglycon 3 provided aurisides A (1) and B (2).

    DOI: 10.24496/tennenyuki.48.0_205

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  • 8 Studies on Antitumor Mechanism of Aplyronine A

    Kuroda Takeshi, Suenaga Kiyotake, Handa Tomohisa, Miya Saori, Okamoto Kazuhito, Kanematsu Kengo, Sakakura Akira, Yamada Kiyoyuki, Hirata Kunio, Takata Masaki, Kato Kenichi, Muraoka Shin, Yamamoto Masaki, Tanaka Hiroshi, Kigoshi Hideo

    Symposium on the Chemistry of Natural Products, symposium papers   ( 48 )   43 - 48   2006.9

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    The interaction between actin and aplyronine A, a potent antitumor and actin-depolymerizing substance of marine origin, was investigated by photoaffinity labeling experiments and X-ray structure analysis of actin complex with aplyronine A. Photoaffinity probes consisting of a side-chain portion of aplyronine A as a ligand, a diazirine moiety as a photoaffinity group, and a fluorophor as a detecting group were synthesized. Photolabeling experiments between actin and the probe were carried out. Actin was successfully photolabeled by the fluorescent probe and visualized clearly. The present results provide the first chemical evidence for the direct interaction between actin and the side-chain portion of aplyronine A. X-ray structure analysis of actin-aplyronine A complex was carried out. The analysis showed that Aplyronine A bound to a hydrophobic cleft between subdomains 1 and 3 of actin. The structural feature is that the trimethylserine moiety protrudes toward the bulk solvent region.

    DOI: 10.24496/tennenyuki.48.0_43

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  • Enantioselective synthesis of aurisides A and B, cytotoxic macrolide glycosides of marine origin Reviewed

    Kiyotake Suenaga, Hiroshi Hoshino, Takanori Yoshii, Kazunori Mori, Hiroki Sone, Yuhki Bessho, Akira Sakakura, Ichiro Hayakawa, Kiyoyuki Yamada, Hideo Kigoshi

    TETRAHEDRON   62 ( 33 )   7687 - 7698   2006.8

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    DOI: 10.1016/j.tet.2006.05.077

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  • Synthesis and biological activity of mycalolide analogs Reviewed

    Kiyotake Suenaga, Tomoyuki Kimura, Takeshi Kuroda, Keita Matsui, Saori Miya, Satomi Kuribayashi, Akira Sakakura, Hideo Kigoshi

    TETRAHEDRON   62 ( 35 )   8278 - 8290   2006.8

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    DOI: 10.1016/j.tet.2006.06.046

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  • P-81 ENANTIOSELECTIVE POLYENE HALOCYCLIZATION INDUCED BY NUCLEOPHILIC CHIRAL PHOSPHINES

    Sakakura Akira, Ukai Atsushi, Ishihara Kazuaki

    International Symposium on the Chemistry of Natural Products   2006   "P - 81"   2006.7

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    DOI: 10.24496/intnaturalprod.2006.0__P-81_

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  • Development of environmentally benign catalytic dehydration process Reviewed

    Akira Sakakura, Kazuaki Ishihara

    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN   64 ( 6 )   651 - 663   2006.6

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    DOI: 10.5059/yukigoseikyokaishi.64.651

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  • Chiral 1,1 '-binaphthyl-2,2 '-diammonium salt catalysts for the enantioselective Diels-Alder reaction with alpha-acyloxyacroleins Reviewed

    Akira Sakakura, Kenji Suzuki, Kazuhiko Nakano, Kazuaki Ishihara

    ORGANIC LETTERS   8 ( 11 )   2229 - 2232   2006.5

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    DOI: 10.1021/ol060490l

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  • Study of the interaction between actin and antitumor substance aplyronine A with a novel fluorescent photoaffinity probe Reviewed

    Takeshi Kuroda, Kiyotake Suenaga, Akira Sakakura, Tomohisa Handa, Kazuhito Okamoto, Hideo Kigoshi

    Bioconjugate Chemistry   17 ( 2 )   524 - 529   2006.3

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    DOI: 10.1021/bc050324i

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  • Bulky diarylammonium arenesulfonates as mild and extremely active dehydrative ester condensation catalysts Reviewed

    Akira Sakakura, Shoko Nakagawa, Kazuaki Ishihara

    Tetrahedron   62 ( 2-3 )   422 - 433   2006.1

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    DOI: 10.1016/j.tet.2005.09.059

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  • P-12 Efficient Synthesis of Oxazolines and Thiazolines Using Molybdenum Oxide-Catalyzed Dehydrative Cyclization Reaction

    Sakakura Akira, Kondo Rei, Umemura Shuhei, Ishihara Kazuaki

    Symposium on the Chemistry of Natural Products, symposium papers   ( 47 )   475 - 480   2005.9

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    Oxazoline, oxazole, thiazoline, and thiazole rings are important constituents of numerous bioactive natural products and pharmaceuticals. The biosynthesis of many naturally occurring oxazolines and thiazolines appears to involve the dehydrative cyclization of serine, threonine, and cysteine residues. Oxazoles and thiazoles are synthesized by the oxidation of oxazolines and thiazolines, respectively. We describe here a biomimetic synthesis of oxazolines and thiazolines catalyzed by molybdenum (IV or VI) oxides, their mode of cyclization is retentive at the β-position. In the course of screening various metal oxides as catalysts for the dehydrative cyclization of dipeptides 1a and 1b, we found that molybdenum oxides had good catalytic activities. Interestingly, the ammonium salts of molybdenum(VI) oxides, (NH_4)_6Mo_7O_<24>・4H_2O and (NH_4)_2MoO_4, exhibited remarkable catalytic activities and gave oxazolines 2a and 2b in a short reaction time, along with small amounts of 3a and 3b. Next, we examined the dehydrative cyclization of cysteine derivatives 4a and 4b to thiazolines 5a and 5b using molybdenum oxides as catalysts. In the case of the dehydrative cyclization of 4a, (NH_4)_6Mo_7O_<24>・4H_2O, (NH_4)_2MoO_4 and MoO_2(acac)_2 showed excellent catalytic activities. MoO_2(acac)_2 could catalyze the dehydrative cyclization of 4b, to give 5b in 70% yield along with 5c (15%). To the best of our knowledge, this is the first example of the catalytic dehydrative cyclization of dipeptide substrates that include serine, threonine, and cysteine residues. A key synthetic intermediate 11 of hennoxazole A and bis(oxazoline)s 13a and 13b were synthesized by the dehydrative cyclization using molybdenum oxide catalysts. In addition, polyaniline-supported MoO_2(acac)_2 could easily be recovered and reused.

    DOI: 10.24496/tennenyuki.47.0_475

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  • Selective synthesis of phosphate monoesters by dehydrative condensation of phosphoric acid and alcohols promoted by nucleophilic bases Reviewed

    Akira Sakakura, Mikimoto Katsukawa, Kazuaki Ishihara

    Organic Letters   7 ( 10 )   1999 - 2002   2005.5

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    DOI: 10.1021/ol0504796

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  • Molybdenum oxides as highly effective dehydrative cyclization catalysts for the synthesis of oxazolines and thiazolines Reviewed

    Akira Sakakura, Rei Kondo, Kazuaki Ishihara

    Organic Letters   7 ( 10 )   1971 - 1974   2005.5

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    DOI: 10.1021/ol050543j

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  • Bulky diarylammonium arenesulfonates as selective esterification catalysts Reviewed

    Kazuaki Ishihara, Shoko Nakagawa, Akira Sakakura

    Journal of the American Chemical Society   127 ( 12 )   4168 - 4169   2005.3

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    DOI: 10.1021/ja050223v

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  • Formal synthesis of optically active ingenol via ring-closing olefin metathesis Reviewed

    Kazushi Watanabe, Yuto Suzuki, Kenta Aoki, Akira Sakakura, Kiyotake Suenaga, Hideo Kigoshi

    Journal of Organic Chemistry   69 ( 23 )   7802 - 7808   2004.11

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    DOI: 10.1021/jo048833l

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  • Spongiacysteine, a novel cysteine derivative from marine sponge Spongia sp. Reviewed

    Keiko Kobayashi, Hiroki Shimogawa, Akira Sakakura, Toshiaki Teruya, Kiyotake Suenaga, Hideo Kigoshi

    Chemistry Letters   33 ( 10 )   1262 - 1263   2004.10

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    DOI: 10.1246/cl.2004.1262

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  • 99(P-32) Formal Synthesis of Optically Active Ingenol

    Watanabe Kazushi, Suzuki Yuto, Aoki Kenta, Sakakura Akira, Suenaga Kiyotake, Kigoshi Hideo

    Symposium on the Chemistry of Natural Products, symposium papers   ( 46 )   569 - 574   2004.10

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    Ingenol is a diterpenoid isolated from Euphorbia ingens, possessing a bicyclo[4.4.1]undecane skeleton with a highly strained inside, outside-intrabridgehead stereochemistry. Several strategies for construction of the unique skeleton have been reported, however, direct cyclization to the inside, ousidet-bicyclo[4.4.1]undecane system has not been reported. Recently, two total syntheses in a racemic form using the aforementioned strategies were reported by Winkler and Tanino-Kuwajima. We would like to report the construction of strained carbon skeletons of ingenol by direct cyclization with ring-closing olefin metathesis (RCM). With well-designed diene compounds 4, 23, and 24, RCM was found to be applicable to the formation of a highly strained skeleton of ingenol, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of ketone 21 with an allylic chloride unit and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 17, the key intermediate aldehyde 27 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.

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  • 58(P-35) Synthesis and Biological Activities of Aplyronine A and the Related Compounds

    Suenaga K., K. Takeshi, Handa T., Miya S., K. Kengo, Sakakura A., Yamada K., K. Hideo, Hirata K., Takata M., Kato K., Muraoka S., Yamamoto M., Tanaka H.

    Symposium on the Chemistry of Natural Products, symposium papers   ( 46 )   323 - 328   2004.10

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    Aplyronine A (1) is a potent antitumor macrolide isolated from the sea hare Aplysia kurodai, and mycalolide B (2) is a cytotoxic and antifungal macrolide isolated from a sponge of the genus Mycale. These macrolides interact with actin, one of the major proteins in cytoskeleton. We achieved total synthesis of aplyronine A (1) and its analogs and investigated the structure-activity relationships. We improved the synthesis of the side chain portion of aplyronine A (1) by using the Paterson aldol reaction and subsequent stereoselective reduction with Me_4NBH(OAc)_3 as key steps. The synthetic analogs 3 and 4 that only consists of the side chain part of aplyronine A (1) and mycalolide B (2) turned out to exhibit a strong actin depolymerizing activity, considering the size of the molecule. This result revealed that the side chain portion in aplyronine A (1) and mycalolide B (2) was responsible for the potent activity of 1 and 2. Analysis of the interaction of aplyronine analogs, such as 30 and 31, with actin by a photoaffinity labeling method has been carried out. Crystallization and X-ray structure analysis of actin complex with aplyronine A (1) also are in progress.

    DOI: 10.24496/tennenyuki.46.0_323

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  • Jolkinolide D pharmacophore: Synthesis and reaction with biomolecules Reviewed

    Akira Sakakura, Yui Takayanagi, Hiroki Shimogawa, Hideo Kigoshi

    Tetrahedron   60 ( 33 )   7067 - 7075   2004.8

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    DOI: 10.1016/j.tet.2003.08.080

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  • Synthesis and actin-depolymerizing activity of mycalolide analogs Reviewed

    Kiyotake Suenaga, Saori Miya, Takeshi Kuroda, Tomohisa Handa, Kengo Kanematsu, Akira Sakakura, Hideo Kigoshi

    Tetrahedron Letters   45 ( 28 )   5383 - 5386   2004.7

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    DOI: 10.1016/j.tetlet.2004.05.078

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  • Nonspecificity Induces Chiral Specificity in the Folding Transition of Giant DNA Reviewed

    Michiko Ito, Akira Sakakura, Naomi Miyazawa, Shizuaki Murata, Kenichi Yoshikawa

    Journal of the American Chemical Society   125 ( 42 )   12714 - 12715   2003.10

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    DOI: 10.1021/ja036745x

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  • 106(P-60) Jolkinolide D Pharmacophore : Synthesis and Reaction with Amino Acids, Nucleosides, and DNA

    Sakakura Akira, Takayanagi Yui, Shimogawa Hiroki, Kigoshi Hideo

    Symposium on the Chemistry of Natural Products, symposium papers   ( 44 )   623 - 628   2002.9

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    Jolkinolide D (1) is a diterpenoid isolated from Euphorbia jolkini Boiss in 1974, and its stereostructure was recently determined by X-ray crystallographic analysis. It inhibited tumor invasion into the basement membrane and induced apoptosis in tumor cells. Jolkinolide D (1) has a γ,δ-unsaturated-β-hydroxy-α-methylene lactone unit as the pharmacophore structure, which suggests that jolkinolide D (1) might alkylate biomolecules such as proteins and DNA irreversibly. Since there are no other compounds that have the pharmacophore, reactivities of the unit toward nucleophiles have not hitherto been investigated. For the purpose of obtaining preliminary information on the chemical modification of biomolecules with jolkinolide D (1), jolkinolide D pharmacophore (2) was synthesized from 6-(tert-butyldimethylsilyloxy)-3-methyl-2-cyclohexenone (3) and 2-iodoallylalcohol (4), and its reactivity toward amino acids, nucleosides, and DNA was investigated. It was found that the order of reactivity of jolkinolide D pharmacophore (2) toward the nucleophiles in the amino acids at pH 7.5 is the thiol group in L-cysteine and glutathione > the imidazolyl group in L-histidine, the α-amino groups in amino acids > the carboxyl groups in amino acids. Jolkinolide D pharmacophore (2) alkylated 2'-deoxyguanosine at the N-1 position (pH 7.5) and thymidine at the N-3 position (pH 8.7), and modified DNA at the same sites in lower yields.

    DOI: 10.24496/tennenyuki.44.0_623

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  • Jolkinolide D pharmacophore: Synthesis and reaction with amino acids, nucleosides, and DNA Reviewed

    Akira Sakakura, Yui Takayanagi, Hideo Kigoshi

    Tetrahedron Letters   43 ( 34 )   6055 - 6058   2002.8

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    DOI: 10.1016/S0040-4039(02)01195-4

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  • Effect of molecular sieves in the liquid-phase synthesis of nucleotides via the phosphoramidite method Reviewed

    Yoshihiro Hayakawa, Akiyoshi Hirata, Jun-Ichiro Sugimoto, Rie Kawai, Akira Sakakura, Masanori Kataoka

    Tetrahedron   57 ( 42 )   8823 - 8826   2001.10

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    DOI: 10.1016/S0040-4020(01)00880-8

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  • A facile synthesis of 5′-end solid-anchored, 3′-end free oligodeoxyribonucleotides via the (5′→3′)-elongated phosphoramidite strategy Reviewed

    Akira Sakakura, Yoshihiro Hayakawa

    Nucleosides, Nucleotides and Nucleic Acids   20 ( 3 )   213 - 227   2001

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    DOI: 10.1081/NCN-100002082

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  • Acid/azole complexes as highly effective promoters in the synthesis of DNA and RNA oligomers via the phosphoramidite method Reviewed

    Y. Hayakawa, R. Kawai, A. Hirata, J. I. Sugimoto, M. Kataoka, A. Sakakura, M. Hirose, R. Noyori

    Journal of the American Chemical Society   123 ( 34 )   8165 - 8176   2001

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    DOI: 10.1021/ja010078v

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  • A novel synthesis of oligonucleotide-peptide conjugates with a base- labile phosphate linker between the two components according to the allyl- protected phosphoramidite strategy Reviewed

    Akira Sakakura, Yoshihiro Hayakawa

    Tetrahedron   56 ( 26 )   4427 - 4435   2000.6

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    DOI: 10.1016/S0040-4020(00)00376-8

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  • An efficient synthesis of nucleotides via the phosphoramidite method using a triflic acid salt of an imidazole-related compound as a promoter.

    A. Sakakura, M. Kataoka, R. Kawai, Y. Hayakawa

    Nucleic acids symposium series   ( 44 )   137 - 138   2000

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    DOI: 10.1093/nass/44.1.137

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  • A novel approach to oligodeoxyribonucleotides bearing phosphoric acid esters at the 3'-terminals via the phosphoramidite method with allyl protection: An efficient synthesis of base-labile nucleotide-amino acid and - peptide conjugates Reviewed

    Akira Sakakura, Yoshihiro Hayakawa, Hitoshi Harada, Masaaki Hirose, Ryoji Noyori

    Tetrahedron Letters   40 ( 23 )   4359 - 4362   1999.6

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    DOI: 10.1016/S0040-4039(99)00748-0

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  • Aplyronine A, a potent antitumor substance of marine origin, aplyronines B and C, and artificial analogues: Total synthesis and structure-cytotoxicity relationships Reviewed

    Hideo Kigoshi, Kiyotake Suenaga, Tsuyoshi Mutou, Takeshi Ishigaki, Toshiyuki Atsumi, Hiroyuki Ishiwata, Akira Sakakura, Takeshi Ogawa, Makoto Ojika, Kiyoyuki Yamada

    Journal of Organic Chemistry   61 ( 16 )   5326 - 5351   1996.8

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    DOI: 10.1021/jo9606113

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  • Absolute stereochemistry and synthesis of aplyronines B and C, the congeners of aplyronine A, a potent antitumor substance of marine origin Reviewed

    Kiyotake Suenaga, Takeshi Ishigaki, Akira Sakakura, Hideo Kigoshi, Kiyoyuki Yamada

    Tetrahedron Letters   36 ( 28 )   5053 - 5056   1995.7

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    DOI: 10.1016/0040-4039(95)00921-X

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  • Total synthesis of aplyronine A, a potent antitumor substance of marine origin Reviewed

    Kigoshi Hideo, Ojika Makoto, Ishigaki Takeshi, Suenaga Kiyotake, Mutou Tsuyoshi, Sakakura Akira, Ogawa Takeshi, Yamada Kiyoyuki

    Journal of the American Chemical Society   116 ( 16 )   7443 - 7444   1994.8

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  • Synthetic Studies on Aplyronine A, a Potent Antitumor Substance of Marine Origin: Stereocontrolled Synthesis of the C21-C34 Segment Reviewed

    Hideo Kigoshi, Makoto Ojika, Kiyotake Suenaga, Tsuyoshi Mutou, Junko Hirano, Akira Sakakura, Takeshi Ogawa, Masanori Nisiwaki, Kiyoyuki Yamada

    Tetrahedron Letters   35 ( 8 )   1247 - 1250   1994.2

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    DOI: 10.1016/0040-4039(94)88035-2

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  • 23 STEREOCHEMISTRY AND SYNTHETIC STUDY OF APLYRONINE A, AN ANTITUMOR MACROLIDE OF MARINE ORIGIN

    Kigoshi H., Ojika M., Ishigaki T., Suenaga K., Muto T., Sakakura A., Ogawa T., Nisiwaki M., Tsukada I., Yamada K.

    Symposium on the Chemistry of Natural Products, symposium papers   ( 35 )   174 - 178   1993.9

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    Aplyronine A (1) is a potent antitumor macrolide isolated as a minute component from the sea hare Aplysia kurodai. The gross structure of 1 was determined by the spectral analysis and chemical degradation. We report herein the absolute stereostructure of 1 and the result of the synthetic study. Chemical degradation of 1 afforded five fragments 2-6. Enantioselective syntheses of the fragments 4a and 5a were performed to disclose the absolute stereochemistry of seven chiral centers (C7-C10, C13, C17, and C19). HPLC analyses of the fragments 2 and 3 using chiral columns disclosed that N,N,O-trimethylserine and N,N-dimethylalanine moieties of 1 were scalemic mixtures (S:R=52:48 for 2; 72:28 for 3). On the basis of the result of the previous and present studies, the absolute stereostructure of aplyronine A (1) was elucidated unambiguously. The synthetic study of 1 was carried out using the Evans aldol reaction and the Sharpless epoxidation reaction as key steps. Starting from N-propionylurethane 11, the C5-C20 segment 13 and the C21-C34 segment 16 were synthesized. The Julia coupling reaction of 13 with 16 followed by four-carbons homologation and lactonization provided 24-membered lactone 17.

    DOI: 10.24496/tennenyuki.35.0_174

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MISC

  • Copper(II) Triflimide

    Akira Sakakura, Kazuaki Ishihara

    April 2017   1 - 4   2017

  • Hetero-Diels-Alder Reactions

    K. Ishihara, A. Sakakura

    Comprehensive Organic Synthesis: Second Edition   5   409 - 465   2014.2

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    DOI: 10.1016/B978-0-08-097742-3.00510-3

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  • Intermolecular Diels-Alder Reactions

    K. Ishihara, A. Sakakura

    Comprehensive Organic Synthesis: Second Edition   5   351 - 408   2014.2

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    DOI: 10.1016/B978-0-08-097742-3.00509-7

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  • 6.10 C-C Bond Formation: Diels-Alder Reaction

    K. Ishihara, A. Sakakura

    Comprehensive Chirality   6   264 - 292   2012.9

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    DOI: 10.1016/B978-0-08-095167-6.00610-8

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  • [4+2]-Cycloaddition Reactions

    Akira Sakakura, Kazuaki Ishihara

    Science of Synthesis, Stereoselective Synthesis 3: Stereoselective Pericyclic Reactions, Cross Coupling, and C–H and C–X Activation   67 - 123   2011

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  • A facile solid-phase synthesis of oligodeoxyribo-nucleotides and their amino acid conjugates via the allyl-protected phosphoramidite approach with benzimidazolium triflate as a promoter

    Y Hayakawa, A Sakakura, SB Heidenhain, M Kataoka

    CHEMISTRY OF NUCLEIC ACID COMPONENTS   2   105 - 108   1999

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Presentations

  • Development of convergent synthetic method toward natural products with bicyclo[3.2.1]octane core

    Naochika Matsumaru, Haruki Mizoguchi, Akira Sakakura

    2023.3.25 

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    Event date: 2023.3.22 - 2023.3.25

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  • Toward the biomimetic synthesis of grayanane diterpenoids

    Hidetoshi Kamada, Haruki Mizoguchi, Akira Sakakura

    2023.3.25 

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    Event date: 2023.3.22 - 2023.3.25

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  • Asymmetric Direct Mannich Reaction of α-Ketoesters Catalyzed by Sulfonamide-substituted Chiral Lewis Acid Catalyst

    Takeru Abe, Haruki Mizoguchi, Akira Sakakura

    2023.3.24 

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    Event date: 2023.3.22 - 2023.3.25

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  • Towards the diversity-oriented synthesis of indole diterpenes

    2020.9.23 

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    Event date: 2020.9.22 - 2020.9.24

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  • ジアステレオ選択的Henry反応を鍵とするマンザシジンBの形式全合成

    荒木雄也, 三好夏美, 森本一樹, 溝口玄樹, 坂倉彰

    第61回天然有機化合物討論会  2019.9.11 

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    Event date: 2019.9.11 - 2019.9.13

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  • ゲラニル誘導体のバイオミメティックなブロモ環化反応に有効なチオウレア触媒

    坂倉彰, 寺崎美幸, 塩本啓一, 溝口玄樹

    第60回天然有機化合物討論会  2018.9.27 

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    Event date: 2018.9.26 - 2018.9.28

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  • Development of a conjunctive cross-coupling of vinylboronic ester ate-complex with ketene

    2022.3.26 

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  • Synthesis of polycyclic skeletons including bicyclo[3.2.1]octane ring

    2022.3.26 

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  • Construction of seven-membered carbocycles using 1,2-metallate rearrangement of cyclopropenylboronic ester ate-complex

    2022.3.24 

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  • Asymmetric synthesis of b-hydroxy quaternary amino acids via chiral Lewis acid-catalyzed direct aldol reaction

    2022.3.24 

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  • Mechanistic investigation and substrate scope evaluation of an aryne-triggered 1,2-metallate rearrangement of vinylboronic esters

    2021.3.19 

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  • Enantioselective Diels-Alder Reaction of 3-Nitrocoumarins Promoted by Chiral organoammonium Salt Catalysts

    2021.3.19 

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  • Synthesis of highly substituted boronic ester utilized aryne-triggered 1,2-metallate rearrangement of vinylboronic ester

    2021.3.19 

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  • Design of Chiral Lewis Acid Catalyst for the Asymmetric Direct Mannich Reaction of α-Ketoesters

    2021.3.19 

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  • Stereoselective Construction of Contiguous Asymmetric Quaternary Carbon Centers of Indole Terpenes

    2021.3.19 

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  • Development of an intramolecular C‒H silylmethylation of benzyl alcohol derivatives utilizing photoexcited palladium complex

    2021.3.19 

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  • Synthetic Study of Terpendole E: Stereoselective Construction of Contiguous Asymmetric Quaternary Carbon Centers

    2020.3.25 

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  • Expeditious Construction of Highly Oxygenated Terpenoid Skeletons Utilizing Desymmetrizing Reductive-Heck Cyclization

    2020.3.23 

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  • Investigation of Stereoselective Construction of α,α-Disubstituted β-Hydroxy-α-Amino Acid Structure Using Chiral Lewis Acid Catalysts

    2020.3.23 

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  • Synthesis and Biological Evaluation of Coprinoferrin

    2020.3.22 

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  • Development of a Conjunctive-cross Coupling of Alkenylboronic Ester Ate-complex Enabled by an Aryne Triggered Strain-release 1,2-Metallate Rearrangement

    2020.3.22 

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  • Stereoselective construction of highly substituted cyclopropylboronic esters enabled by 1,2-metallate rearrangement of boron-ate complex

    2020.3.22 

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  • アルテミシジン類のシクロペンタン部の立体選択的合成研究

    早川一郎, 永易杏菜, 坂倉彰

    第116回有機合成シンポジウム2019【秋】  2019.11.1 

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  • Synthetic Study of Yuzurimine-Type Alkaloids: Stereoselective Construction of Heterocyclic Portion

    2019.3.17 

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  • Enantioselective 1,3-Dipolar Cycloaddition of α-Substituted acroleins with Nitrones Catalyzed by Chiral Organoammonium salts

    2019.3.17 

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  • Investigation of Asymmetric Direct Mannich Reaction of α-Ketoesters Promoted by Chiral Lewis Acid Catalyst

    2019.3.17 

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  • Synthetic study of manzacidins A, B and C based on diastereoselective Henry reaction

    2019.3.17 

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  • Synthetic Studies of Altemicidin-type Alkaloids: Stereoselective Construction of Cyclopentane Portion

    2019.3.17 

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  • キラルなブレンステッド酸触媒を用いた3-ニトロクマリンの不斉Diels–Alder反応と速度論的光学分割

    坂倉彰, 藤井裕大, 中尾亮太, 早川一郎, 溝口玄樹

    第11回有機触媒シンポジウム  2018.12.3 

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Industrial property rights

  • γ-チューブリン阻害剤

    臼井健郎, 早川一郎, 畑中大成, 坂倉 彰

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    Application no:特願2018-143346  Date applied:2018.7.31

    Announcement no:特開2020- 019732  Date announced:2020.2.6

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  • ピロリン酸エステル化合物、ビスリン酸エステル化合物及び触媒

    石原一彰, 坂倉 彰

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    Application no:特願2012-160092  Date applied:2012.7.19

    Patent/Registration no:特許第6168665号  Date registered:2017.7.7  Date issued:2017.7.26

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  • 新規なジヒドロピラン化合物及びその製法

    石原一彰, 坂倉 彰

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    Application no:特願2012-032401  Date applied:2012.2.17

    Announcement no:特開2013-166736  Date announced:2013.8.29

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  • α-ヒドロキシカルボン酸アミド化合物の製法及び新規なアリールボロン酸化合物

    石原一彰, 坂倉 彰

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    Application no:特願2012-032400  Date applied:2012.2.17

    Patent/Registration no:特許第5881189号  Date registered:2016.2.12  Date issued:2016.3.9

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  • エステルの加水分解によるカルボン酸及びアルコールの製造方法

    石原一彰, 坂倉 彰, 越仮良樹

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    Application no:特願2011-289040  Date applied:2011.12.28

    Patent/Registration no:特許第6061399号  Date registered:2016.12.22  Date issued:2017.1.18

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  • カルボン酸無水物の製造方法及びアリールボロン酸化合物

    石原一彰, 坂倉 彰

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    Application no:特願2009-058720  Date applied:2009.3.11

    Patent/Registration no:特許第5747330号  Date registered:2015.5.22  Date issued:2015.7.15

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  • 水中での脱水縮合によるエステル製造方法

    石原一彰, 坂倉 彰

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    Application no:特願2009-058719  Date applied:2009.3.11

    Announcement no:特開2010-209027  Date announced:2010.9.24

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  • エステルの製造法

    石原一彰, 坂倉 彰, 木幡康則

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    Application no:特願2007-213235  Date applied:2007.8.20

    Announcement no:特開2009-046415  Date announced:2009.3.5

    Patent/Registration no:特許第5419119号  Date registered:2013.11.29  Date issued:2014.2.19

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  • リン酸エステルの製造方法

    石原一彰, 坂倉 彰, 勝川幹基, 井上佳尚

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    Application no:特願2007-42875  Date applied:2007.2.22

    Announcement no:特開2008-201764  Date announced:2008.9.4

    Patent/Registration no:特許第5067752号  Date registered:2012.8.24  Date issued:2012.11.7

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  • リン酸モノエステル製造用触媒及びリン酸モノエステルの製造方法

    石原一彰, 坂倉 彰

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    Application no:PCT/JP2006/324852  Date applied:2006.12.13

    Announcement no:WO2007/097100  Date announced:2007.8.30

    Patent/Registration no:特許第4210764号  Date registered:2008.11.7  Date issued:2009.1.21

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  • チアゾリン製造用触媒、チアゾリン化合物の製法、オキサゾリン製造用触媒及びオキサゾリン化合物の製法

    石原一彰, 坂倉 彰

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    Application no:特願2006-050064  Date applied:2006.2.27

    Announcement no:特開2007-222851  Date announced:2007.9.6

    Patent/Registration no:特許第4178251号  Date registered:2008.9.5  Date issued:2008.11.12

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  • ディールス・アルダー反応触媒および不斉環化付加生成物の製造方法

    石原一彰, 坂倉 彰

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    Application no:特願2006–050063  Date applied:2006.2.27

    Announcement no:特開2007-222850  Date announced:2007.9.6

    Patent/Registration no:特許第4189500号  Date registered:2008.9.26  Date issued:2008.12.3

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  • エステル製造方法及びエステル化触媒

    石原一彰, 坂倉 彰

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    Application no:PCT/JP2005/004398  Date applied:2005.3.8

    Announcement no:WO2005/085172  Date announced:2005.9.15

    Patent/Registration no:特許第4734607号  Date registered:2011.5.13  Date issued:2011.7.27

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  • オキサゾリン化合物の製法及びチアゾリン化合物の製法

    石原一彰, 坂倉 彰

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    Application no:特願2004-141263  Date applied:2004.5.11

    Announcement no:特開2005-320304  Date announced:2005.11.17

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Awards

  • Asian Core Program Lectureship Award

    2010.11  

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  • Banyu Chemist Award

    2009.12  

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  • 有機合成化学奨励賞

    2008.2  

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  • 日本化学会第86春季年会 若い世代の特別講演賞

    2006.3  

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  • 萬有製薬研究企画賞

    2006.2   有機合成化学協会  

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  • Thieme Chemistry Journal Award

    2006  

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  • 有機合成化学協会東海支部奨励賞

    2005.7  

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Research Projects

  • Development of Methods for Synthesis of Aminosugars by Catalytic Asymmetric Addition Reactions of alpha-Ketoesters

    Grant number:18K05123  2018.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sakakura Akira

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    Grant amount:\4420000 ( Direct expense: \3400000 、 Indirect expense:\1020000 )

    Amino sugars, which are useful antibiotics, have carbon skeleton bearing several hydroxy and amino groups. Since the structures of amino sugars are highly complex, the stereoselective synthesis of amino sugars is quite difficult. In this study, we have developed the methods of stereoselective synthesis of amino sugars by using asymmetric catalyst. As results, we succeeded to develop several enantioselective carbon-carbon bond forming reaction. In addition, we achieved formal total synthesis of manzacidin B, which have carbon skeleton bearing continuous amino and hydroxy groups.

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  • 分子内n-カチオン相互作用を利用した有機分子ルイス酸触媒の精密設計

    Grant number:26105739  2014.04 - 2016.03

    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)  新学術領域研究(研究領域提案型)

    坂倉 彰

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    Grant amount:\7020000 ( Direct expense: \5400000 、 Indirect expense:\1620000 )

    1.カチオン性キラルホウ酸エステル触媒の精密設計
    我々はこれまでに,配位子のルイス塩基性部位と金属カチオンとの相互作用(n-カチオン相互作用)を鍵とする分子設計により,優れた基質一般性を示すキラル金属ルイス酸触媒の開発に成功している。この研究を基に,これまであまり研究が進んでいないカチオン性ルイス酸性有機分子触媒の精密設計を行った。分子内のルイス塩基性部位による相互作用によってカチオン性をもたせつつ安定性を確保する触媒設計である。N-アルキルアミノアルコールとホウ酸トリメチルからカチオンホウ酸エステル触媒を調製し,trans-シンナムアルデヒドとシクロペンタジエンのDiels-Alder反応においてその触媒活性を検討した。その結果,収率は低いものの,中程度のエナンチオ選択性でDiels-Alder付加体得ることができた。
    <BR>
    2.亜リン酸エステル-ウレア協働作用型触媒によるエナンチオ選択的ブロモ環化反応の開発
    キラルな亜リン酸エステル-ウレア協働作用型触媒の精密設計に基づき,2-ゲラニルフェノール誘導体のエナンチオ選択的ブロモ環化反応の開発を行った。触媒構造や反応条件を精査した結果,良好なエナンチオ選択性で,対応するブロモ環化生成物を得ることができた。特筆すべきは,2つの環を形成したAB環生成物よりも1つの環のみが形成されたA環生成物の方がエナンチオ選択性が高かったことである。A環生成物が生成する際の遷移状態において,基質のヒドロキシ基と触媒のウレア基とが水素結合を形成することにより,遷移状態の立体配座が適切に制御されたものと考えられる。

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  • Design of High Performance Catalysts Based on Biomimetic Approach

    Grant number:23350039  2011.04 - 2014.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    SAKAKURA Akira

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    Grant amount:\19370000 ( Direct expense: \14900000 、 Indirect expense:\4470000 )

    Based on acid-base combination chemistry, we conducted the rational design of high performance catalysts with functionalities such as weak secondary interaction and acid-base dual activation. Using these catalysts, we developed highly selective synthetic processes. For example, we achieved dehydrative ester condensation in water using organoammonium catalysts, enantioselective carbon-carbon bond forming reactions (Diels-Alder reaction, polyene cyclization and iodolactonization of unsaturated carboxylic acids) and acylation reaction based on acid-base combination catalysis (cyanoethoxycarbonylation of isatins and dehydrative amide condensation of alpha-hydroxy carboxylic acids).

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  • Design of highly functional catalysts based on acid. base combination chemistry

    Grant number:20245022  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    ISHIHARA Kazuaki, SAKAKURA Akira, HATANO Manabu, UYANIK Muhammet

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    Grant amount:\49660000 ( Direct expense: \38200000 、 Indirect expense:\11460000 )

    Rational design of catalysts is very important to control not only reactivity of target reactions but also chemoselectivity, stereoselectivity, regioselectivity, enantioselectivity, and substrate selectivity. Enzymes almost perfectly control target reactions even in vivo. On the other hand, small molecule artificial catalysts cannot perfectly control reactions. In this research project, the development of new acid. base combined catalysts was performed to attain high level of catalytic functions. As results, we succeeded in the development of several high functional catalysts based on acid. base combination chemistry.

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  • カルボン酸の触媒的脱水縮合による酸無水物合成プロセスの開拓

    Grant number:20655019  2008

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    坂倉 彰

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    Grant amount:\3600000 ( Direct expense: \3600000 )

    カルボン酸無水物は、DMAP触媒によるエステル化反応を始めとする様々な反応に用いられている有用なアシル化剤である。カルボン酸無水物は、カルボン酸の触媒的脱水縮合で合成されるのが最も理想的である。しかし,これまでのところカルボン酸の直接脱水縮合に有効な触媒は開発されておらず,カルボン酸塩化物やジシクロヘキシルカルボジイミドのような脱水縮合剤を用いるのが一般的である。これらの従来法では,副生成物として腐食性の塩化水素が発生したり,多量の副生成物が生成したりするという問題がある。そこで,本萌芽研究では直接脱水縮合によるカルボン酸無水物の合成に有効な触媒の開発を行った。
    カルボン酸の活性化に有効な触媒を中心に詳細な検討を行った結果,いくつかのアリールボロン酸がカルボン酸間の直接脱水縮合に対して良好な触媒活性を示すことを見出した。特に,2,6位にジアルキルアミノメチル基やトリアルキルアンモニウムメチル基を持つアリールボロン酸が優れた触媒活性を示し,炭化水素などの非極性溶媒中で脱水加熱還流させることにより,対応するカルボン酸無水物が良好な収率で得られた。例えば,2,6-ビス[(N,N-ジイソプロピルアミノ)メチル]フェニルボロン酸触媒(10 mol%)存在下,ピロメリット酸のオクタン溶液を12時間脱水加熱還流させることにより,耐熱性ポリイミド樹脂の原料であるピロメリット酸無水物をほぼ定量的に合成することに成功した。また,低収率ではあるがモノカルボン酸の分子間脱水縮合によるカルボン酸無水物の合成にも成功した。

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  • 生物活性物質合成を指向した環境低負荷型触媒的脱水反応の開拓

    Grant number:18750082  2006 - 2007

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    坂倉 彰

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    Grant amount:\3700000 ( Direct expense: \3700000 )

    高効率的な触媒的脱水縮合反応(脱水環化反応)の開発およびそれを利用した有用生物活性物質の合成研究を行った。多くの生物活性物質に含まれるチアゾリンは、システイン残基の脱水環化によって合成できるが、C5エキソメチン部位のラセミ化が深刻な問題である。本研究では、このラセミ化を引き起こすことなくシステイン残基の脱水環化を促進できる触媒として、酸化モリブデンービスキノリノラート錯体の開発に成功した。本触媒を用いる合成法により、生物活性物質の合成に有効なチアゾリンやオキサゾリンを含むビルディングブロックが効率よく簡便に合成できる。
    リン酸モノエステルはリン酸とアルコールの触媒的脱水縮合によって合成するのがもっとも理想的である。昨年度開発した過酸化レニウム触媒法に引き続き、新規なリン酸の脱水縮合法の開発を行った結果、ホスファゼン塩基が優れた触媒活性を示し、リン酸モノエステルが選択的に合成できることを見出した。本研究成果は、有機触媒によるリン酸の脱水縮合としての初の成功例であり、核酸塩基部を保護しなくてもヌクレオシドの5'水酸基が選択的にリン酸化できるのが特長である。
    DMAP触媒を用いた酸無水物によるアルコールのアシル化が無塩基・無溶媒条件下で効率よく進行することを見出した。本反応条件下、酸に不安定な3級アルコールや反応性の低いフェノール類、難溶性のポリオールなどのエステルが高収率で合成できた。また、ピバル酸無水物を用いることにより、無塩基・無溶媒条件下でのカルボン酸とアルコールの直接エステル化にも成功した。無塩基・無溶媒で実施できるため、小規模な反応容器で大量のエステルが合成でき、極めて実用性の高いエステル合成法である。

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  • Development of environmentally benign and highly active acid-base catalysts and their synthetic application

    Grant number:15205021  2003 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    ISHIHARA Kazuaki, SAKAKURA Akira, HATANO Manabu

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    Grant amount:\51480000 ( Direct expense: \39600000 、 Indirect expense:\11880000 )

    The design of small but highly functional artificial catalysts is very important for practical organic synthesis. We have succeeded in the rational design of small and simple catalysts and related reactions based on acid-base combination chemistry. Acid-base combined catalysts can be classified into three types: (1) acid-base combined salt catalysts (Type A), (2) conjugate acid-base catalysts (Type B), and (3) non-conjugate acid-base catalysts (Type C):
    1. Acid-base combined salt catalysts (Type A)
    1-1. Bronsted acid-base combined salt catalysts (Type A-1): bulky diarylammonium pentafluorobenzenesulfonates as mild and extremely active dehydrative ester condensation catalysts; chiral ammonium alkanesulfonates as asymmetric Diels-Alder catalysts
    1-2. Lewis acid-base combined salt catalysts and reagents (Type A-2): magnesium ate complexes derived from Grignard reagents and alkyllithium as highly alkyl-selective reagents to ketones; zinc ate complexes as catalysts for the highly alkyl-selective addition of Grignard reagents to ketones and aldimines
    1-3. Cation-anion pair catalysts (Type A-3): lithium N, N-diisopropylamide in Haller-Bauer and Cannizzaro reactions; chiral lithium binaphtholate aqua complex as a highly effective asymmetric catalyst for trimethylsilylcyanation
    1-4. Cation-a complex catalysts (Type A-4): chiral Cu(II)・L-DOPA-derived monopeptide complex as an asymmetric Diels-Alder and Mukaiyama-Michael catalyst
    2. Lewis acid-base conjugate catalysts (Type B): molybdenum oxides as highly effective dehydrative cyclization catalysts directed toward the synthesis of oxazolines and thiazolines (Type B-1(monoconjugation)); zinc(II)・3,3'-diphosphinoyl-BINOLates in the asymmetric addition of organozinc reagents to aldehydes (Type B-2 (triconjugation))
    3. Bronsted acid-Lewis base non-conjugate asymmetric catalysts (separated type) (Type C): L-histidine-derived sulfonamide as a minimal artificial acylase for the kinetic resolution of racemic alcohols
    Thus, we developed new acid-base combined catalysts bearing excellent functions such as dual activation, control of nucleophilicity and basicity, asymmetric induction, hydrophobic effect, and so on. Current research is focused on the development of artificial highly functional catalysts which are superior to natural enzymes.

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  • アクチン脱重合活性をもつ海洋天然有機化合物の探索

    Grant number:15710155  2003 - 2004

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    坂倉 彰

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    Grant amount:\3700000 ( Direct expense: \3700000 )

    アプリロニンAは海洋動物アメフラシから単離された抗腫瘍性物質である。従来の抗腫瘍性物質とは異なり、細胞骨格タンパク質のアクチンの重合・脱重合に関与することは分かっているが、抗腫瘍活性発現の分子機構は現在のところ不明である。そこで、アクチンとアプリロニンAの結合を化学的に明らかにすることを目的として、以下の研究を行った。活性に重要な側鎖部に光反応基と蛍光基を有するプローブ分子を4種類合成し、光親和性標識実験を行ったところ,1つのプローブ分子において,光標識されたアクチンを電気泳動で検出することに成功した。さらに,アプリロニンAとの競合実験により,プローブ分子がアプリロニンAと同じ位置でアクチンに結合していることを明らかにした。また,アクチン-アプリロニンA複合体の結晶化に成功し,放射光を用いて結晶構造解析を行った。その結果,アプリロニンAはアクチンのサブドメイン1と3の間の脂溶性クレフトに結合することが明らかになった。さらに詳細に複合体の構造を検討したところ,これまで報告されているアクチン脱重合マクロリドとは異なり,ラクトン部がサブドメイン1の方を向いて結合していることが分かった。この特徴的な構造がアプリロニンAの強い抗腫瘍性に関係するものと考えられる。
    また、アプリロニンAと同様にアクチンを脱重合するミカロライドBの側鎖部を合成した。このもののアクチン脱重合活性を測定したところ,アプリロニンAに匹敵する非常に強い活性を示した。

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  • アクチン、ホスファターゼなどの生体高分子と複合する有機化合物の創製と反応

    Grant number:13024215  2001 - 2002

    日本学術振興会  科学研究費助成事業  特定領域研究

    木越 英夫, 坂倉 彰

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    Grant amount:\4200000 ( Direct expense: \4200000 )

    有機小分子と生体高分子との相互作用の研究は有機化合物による分子認識機構を解明するとともに医学・生物学の分野では生物活性物質の作用機構解明や医薬品開発につながる必須の研究領域である。今回、対象生体高分子として細胞骨格タンパク質のアクチンと新型のプロテインホスファターゼに着目した。
    海洋動物アメフラシから単離されたアプリロニンAは、細胞骨格タンパク質のアクチンに作用する新しい型の抗腫瘍性物質である。これまでの知見よりアプリロニンAの側鎖部がアクチン脱重合活性に重要な部分構造であることが判明していたので、アプリロニンAの約十分の一の活性を持つ側鎖部人工類緑体に光アフィニティ官能基を導入した誘導体2種を合成した。これらの化合物とアクチンの反応を行ったところ、アクチンを効率良く標識することが明らかとなった。現在は、標識部位の特定のために、標識体の酵素加水分解と断片の構造を検討している。
    最近、9-アントラセンカルボン酸(9AC)に阻害されるこれまでには知られていない型のプロテインホスファターゼが存在していることが報告された。そこで、9AC誘導体を設計・合成し、これらのブロテインホスファターゼ阻害活性を検定した。その結果、3位にリンカーをつけた誘導体は目的とする酵素を阻害することが分かった。
    新型の海洋産細胞毒性物質ハテルマライドNAの構造確定と標的分子検索を目的として、合成研究を行い、提出していた構造を修正した。

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  • Internship in Applied Chemistry (2021academic year) Prophase  - その他

  • Seminar on Applied Chemistry 1 (2021academic year) Prophase  - その他

  • Seminar on Applied Chemistry 2 (2021academic year) Late  - その他

  • Basic Applied Chemistry (2021academic year) Late  - 月3~4,火3~4

  • Research Works for Master Thesis on Applied Chemistry (2021academic year) Year-round  - その他

  • Organic Chemistry and its Exercises 2 (2021academic year) Second semester  - 月3,月4,木1,木2

  • Fundamental Organic Chemistry (2021academic year) 1st and 2nd semester  - 金3,金4

  • Fundamental Organic Chemistry 1 (2021academic year) 1st semester  - 金3,金4

  • Fundamental Organic Chemistry 2 (2021academic year) Second semester  - 金3,金4

  • Organic Chemistry 1 (2021academic year) 1st and 2nd semester  - 金3,金4

  • Organic Chemistry 1 (2021academic year) 1st and 2nd semester  - 金3,金4

  • Organic Chemistry 2 (2021academic year) Second semester  - 月3,月4,木1,木2

  • Organic Chemistry 3 (2021academic year) 1st semester  - 月1,月2,木1,木2

  • Organic Chemistry 4 (2021academic year) 1st semester  - 月1,月2,木1,木2

  • Synthetic Organic Chemistry (2021academic year) Third semester  - 木1,木2

  • Synthetic Organic Chemistry (2021academic year) Third semester  - 木1,木2

  • Industrial Organic Chemistry (2021academic year) Fourth semester  - 木5,木6

  • Industrial Organic Chemistry (2021academic year) Fourth semester  - 木5,木6

  • Advanced Synthetic Chemistry 3 (2021academic year) Concentration  - その他

  • Current Chemistry (2021academic year) Fourth semester  - 月3~4

  • Chemistry of Biological Reactions (2021academic year) Late  - その他

  • Bioorganic Chemistry (2021academic year) Prophase  - 水1~2

  • Seminar in Bioorganic Chemistry (2021academic year) Year-round  - その他

  • Topics in Synthetic Chemistry 3 (2020academic year) Summer concentration  - その他

  • Topics in Synthetic Chemistry 2 (2020academic year) Summer concentration  - その他

  • Topics in Synthetic Chemistry 2 (2020academic year) Second semester  - 金3,金4

  • Topics in Synthetic Chemistry 4 (2020academic year) Summer concentration  - その他

  • Topics in Synthetic Chemistry 5 (2020academic year) Summer concentration  - その他

  • Internship in Applied Chemistry (2020academic year) Prophase  - その他

  • Seminar on Applied Chemistry 1 (2020academic year) Prophase  - その他

  • Seminar on Applied Chemistry 2 (2020academic year) Late  - その他

  • Basic Applied Chemistry (2020academic year) Late  - 月3~4,火3~4

  • Research Works for Master Thesis on Applied Chemistry (2020academic year) Year-round  - その他

  • Organic Chemistry and its Exercises 2 (2020academic year) Second semester  - 月3,月4,木1,木2

  • Fundamental Organic Chemistry (2020academic year) 1st and 2nd semester  - 金3,金4

  • Fundamental Organic Chemistry 2 (2020academic year) Second semester  - 金3,金4

  • Organic Chemistry 2 (2020academic year) Second semester  - 月3,月4,木1,木2

  • Organic Chemistry 3 (2020academic year) 1st semester  - 月1,月2,木1,木2

  • Organic Chemistry 4 (2020academic year) 1st semester  - 月1,月2,木1,木2

  • Synthetic Organic Chemistry (2020academic year) Third semester  - 木1,木2

  • Synthetic Organic Chemistry (2020academic year) Third semester  - 木1,木2

  • Advanced Synthetic Chemistry 7 (2020academic year) Winter concentration  - その他

  • Current Chemistry 2 (2020academic year) Fourth semester  - 月3,月4

  • Chemistry of Biological Reactions (2020academic year) Late  - その他

  • Bioorganic Chemistry (2020academic year) Late  - 水1,水2

  • Seminar in Bioorganic Chemistry (2020academic year) Year-round  - その他

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