金属基板表面を反応場として利用した新しい触媒の開発

2013 Fiscal Year Annual Research Report

• Project Area: Molecule Activation Directed toward Straightforward Synthesis
• Project/Area Number: 25105702
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Research Institution: Osaka University
• Principal Investigator: 有澤 光弘 大阪大学, 薬学研究科(研究院), 准教授 (40312962)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ナノ粒子 / 環境 / パラジウム / 電子顕微鏡 / X線 / カップリング / リガンドフリー

Research Abstract

本申請研究では、既に申請者らが見いだしている硫黄修飾金担持型パラジウム(Sulfur-modified Au-supported Pd: SAPd)の研究成果を礎に、新しい反応場である硫黄修飾金の生成機構や物性等学術的特徴をまとめている。すなわち、今年度は、SAPdが自己組織的多層状Pdナノ粒子触媒であることが分かり、繰返し利用や金属種低漏洩のメカニズムを知る上で重要な知見を得ることに成功した。また、本Pdナノ粒子触媒の粒子径は約5 nmであること、構成物はゼロ価Pd種であることも分かり、今後、更に高活性な触媒や別の金属種のナノ粒子触媒を理論的に製造する道筋を立てることが出来た。ナノ粒子触媒の有用性は古くから知られているが、再現性良く粒子径を整え、化学実験に適応することは難しかった。しかし、SAPd製造方法を用いれば、5 nm程度の高活性Pdナノ粒子触媒を再現性良く化学合成に利用することが出来る。触媒を使用する反応条件は極めて重要であり、適切な反応条件を用いれば、SAPdが炭素(sp2)-水素活性化反応だけでなく、炭素(sp3)-水素活性化反応の触媒になることも分かった。触媒量のゼロ価ナノ粒子触媒が、炭素(sp3)-水素活性化反応の触媒になることは、Pdナノ粒子触媒の汎用性を開くものである。更に、SAPdの利点を応 用し、フローシステム（試作機）の開発に成功した。現在、本試作機から得られたデータを基に、より小電力で、効率の良いフローシステムの製造を進めている。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本研究課題の当初研究目的の達成度は約９０％である。引き続き、次年度でも大きな成果を求めていく。

Strategy for Future Research Activity

SAPd適応反応を拡大するとともに、より高活性なSAPd触媒を開発する。Pd 以外の担持金属(例えば Pt、Ru、Ni、Fe)、Au 以外の基板について も包括的に展開し、環境調和型有機金属触媒を論理的に開発する。

Research Products

• [Journal Article] Rational hopping of a peptidic scaffold into non-peptidic scaffolds: structurally novel potent proteasome inhibitors derived from a natural product, belactosin A (2014)
  • Author(s): Shuhei Kawamura, Yuka Unno, Takatsugu Hirokawa, Akira Asai, Mitsuhiro Arisawa and Satoshi Shuto
  • Journal Title: Chem. Commun. Volume: 50 Pages: 2445-2447
  • DOI: 10.1039 /C3CC48818G
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structurally Novel Highly Potent Proteasome Inhibitors Created by the Structure-Based Hybridization of Non-Peptidic Belactosin Derivatives and Peptide Boronates (2014)
  • Author(s): Shuhei Kawamura, Yuka Unno, Akira Asai, Mitsuhiro Arisawa and Satoshi Shuto
  • Journal Title: J. Med. Chem. Volume: 57 Pages: 2726-2735
  • DOI: 10.1021/jm400542h
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Palladium-Nanoparticle-Catalyzed Direct Ethynylation of Aliphatic Carboxylic Acid Derivatives via C(sp3)–H Bond Functionalization (2014)
  • Author(s): Mohammad Al-Amin, Mitsuhiro Arisawa, Satoshi Shuto, Yusuke Ano, Mamoru Tobisu, Naoto Chatani
  • Journal Title: Adv. Synth. Catal. Volume: 356 Pages: 1631-1637
  • DOI: 10.1002/adsc.201301180
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mitsuhiro ARISAWA (2014)
  • Author(s): Ligand-free Suzuki-Miyaura Coupling with Sulfur-modified Gold-supported Palladium in the Synthesis of a Conformationally-Restricted Cyclopropane Compound Library with Three-Dimensional Diversity
  • Journal Title: ACS Combi. Sci. Volume: 16 Pages: 215-220
  • DOI: 10.1021/co4001138
  • Peer Reviewed
• [Journal Article] One-Pot Ring-Closing Metathesis (RCM)/1,3-Dipolar Cycloaddition by an Assisted Tandem Ruthenium Catalysis for the Synthesis of a Novel Dye of Isoindolo[2,1-a]quinoline Structure. (2013)
  • Author(s): Mitsuhiro ARISAWA
  • Journal Title: Angew. Chem. Int. Ed. Engl. Volume: 52 Pages: 1003-1007
  • DOI: 10.1002/anie.201206765
  • Peer Reviewed
• [Journal Article] Three-Dimensional Structural Diversity-Oriented Peptidomimetics Based on the Cyclopropylic Strain. (2013)
  • Author(s): Akira MIZUNO
  • Journal Title: Org. Lett. Volume: 15 Pages: 1686-1689
  • DOI: 10.1021/ol400469w
  • Peer Reviewed
• [Journal Article] Conformational Restriction Approach to BACE1 Inhibitors II: SAR Study of the Isocytosine Derivatives Fixed with a cis-Cyclopropane Ring. (2013)
  • Author(s): Shuji YONEZAWA
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 23 Pages: 2912-2915
  • DOI: 10.1016/j.bmcl.2013.03.056
  • Peer Reviewed
• [Journal Article] Suzuki–Miyaura cross-coupling reactions using a low-leaching and highly recyclable gold-supported palladium material and two types of microwave equipments. (2013)
  • Author(s): Mohammad AL-AMIN
  • Journal Title: Green Chem. Volume: 15 Pages: 1142-1145
  • DOI: 10.1039/C3GC00063J
  • Peer Reviewed
• [Journal Article] Potent Proteasome Inhibitors Derived from the Unnatural Cis-Cyclopropane Isomer of Belactosin A: Synthesis, Biological Activity, and Mode of Action. (2013)
  • Author(s): Shuhei KAWAMURA
  • Journal Title: J. Med. Chem. Volume: 56 Pages: 3689-3700
  • DOI: 10.1021/jm4002296
  • Peer Reviewed
• [Journal Article] Design and Total Synthesis of Cyclic ADP-4-Thioribose as a Chemically and Biologically Stable Equivalent of Cyclic ADP-Ribose, a Ca2+-Mobilizing Second Messenger (2013)
  • Author(s): Takayoshi TSUZUKI
  • Journal Title: Angew. Chem. Int. Ed. Engl. Volume: 52 Pages: 6633-6637
  • DOI: 10.1002/anie.201302098
  • Peer Reviewed
• [Journal Article] Design Synthesis, and Validation of Peptidomimetics with Three-dimentional Structure Diversity (2013)
  • Author(s): Akira MIZUMO
  • Journal Title: Peptide Science Volume: 49 Pages: 9-10
  • Peer Reviewed
• [Journal Article] DJ-1 cooperates with PYCR1 in cell protection against oxidative stress (2013)
  • Author(s): Tatsuki YASUDA
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 436 Pages: 289-294
  • DOI: Biochem. Biophys. Res. Commun. 2013, 436, 289-294.
  • Peer Reviewed
• [Journal Article] Investigation of the Non-Covalent Binding Mode of Covalent Proteasome Inhibitors around the Transition State by Combined Use of Cyclopropylic Strain-Based Conformational Restriction and Computational Modeling (2013)
  • Author(s): Shuhei KAWAMURA
  • Journal Title: J. Med. Chem. Volume: 56 Pages: 5829-5842
  • DOI: 10.1021/jm400542h
  • Peer Reviewed
• [Journal Article] Development of Second Generation Gold-Supported Palladium Material with Low-Leaching and Recyclable Characteristics in Aromatic Amination (2013)
  • Author(s): Mohmmad AL-AMIN
  • Journal Title: J. Org. Chem. Volume: 78 Pages: 7575-7581
  • DOI: DOI: 10.1021/jo4011415
  • Peer Reviewed
• [Journal Article] Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports (2013)
  • Author(s): Kazuaki NAKADA
  • Journal Title: Bioorg. Med. Chem. Volume: 21 Pages: 4938-4950
  • DOI: Bioorg. Med. Chem. 2013, 21, 4938-4950.
  • Peer Reviewed
• [Journal Article] A fluorescence-based method for evaluating inositol 1,4,5-trisphosphate receptor ligands: Determination of subtype selectivity and partial agonist effects (2013)
  • Author(s): Akihiko TANIMURA
  • Journal Title: Journal of Biotechnology Volume: 167 Pages: 248-254
  • DOI: 10.1016/j.jbiotec.2013.06.012
  • Peer Reviewed
• [Journal Article] Design and synthesis of the stabilized analogs of belactosin A with the unnatural cis-cyclopropane structure (2013)
  • Author(s): Shuhei KAWAMURA
  • Journal Title: Org. Biomol. Chem Volume: 11 Pages: 6615-6622
  • DOI: 10.1039/C3OB41338A
  • Peer Reviewed
• [Journal Article] Conformational restriction approach to β-secretase (BACE1) inhibitors III: Effective investigation of the binding mode by combinational use of X-ray analysis, isothermal titration calorimetry and theoretical calculations (2013)
  • Author(s): Shuji YONEZAWA
  • Journal Title: Bioorg. Med. Chem. Volume: 21 Pages: 6506-6522
  • DOI: Bioorg. Med. Chem. 2013, 21, 6506-6522.
  • Peer Reviewed
• [Journal Article] Preparation of nonracemic bromomethylenecyclopropane and its use in Suzuki-Miyaura coupling; synthesis of the arylmethyl-cis-cyclopropane structure core. (2013)
  • Author(s): Makoto TANABE
  • Journal Title: J. Org. Chem. Volume: 78 Pages: 11714-11720
  • DOI: 10.1021/jo401675z
  • Peer Reviewed
• [Journal Article] Palladium-Catalyzed Arylation of Cyclopropanes via Directing Group-Mediated C(sp3)–H Bond Activation To Construct Quaternary Carbon Centers: Synthesis of cis- and trans-1,1,2-Trisubstituted Chiral Cyclopropanes (2013)
  • Author(s): Naoyuki HOSHIYA
  • Journal Title: Org. Lett. Volume: 15 Pages: 6203-6205
  • DOI: 10.1021/ja00772a052
  • Peer Reviewed
• [Presentation] レゾルビンE2のシクロプロパン環導入による安定等価体の創製 (2014)
  • Author(s): 高倉夕季
  • Organizer: 日本薬学会第１３４年会
  • Place of Presentation: 熊本大学（熊本県）
  • Year and Date: 20140327-20140330
• [Presentation] Pdナノパーティクルを用いたC(sp2)-H結合活性化反応によるベンゾトリアゾール骨格の構築 (2014)
  • Author(s): 高木耕治
  • Organizer: 日本薬学会第１３４年会
  • Place of Presentation: 熊本大学（熊本県）
  • Year and Date: 20140327-20140330
• [Presentation] SAPd触媒を用いたヨウ化アリールへのダブルカルボニル化反応の開発 (2014)
  • Author(s): 谷口敬寿
  • Organizer: 日本薬学会第１３４年会
  • Place of Presentation: 熊本大学（熊本県）
  • Year and Date: 20140327-20140330
• [Presentation] GABAトランスポーターサブタイプ特異的な新規阻害剤候補化合物の薬理活性評価 (2014)
  • Author(s): 井川ありさ
  • Organizer: 日本薬学会第１３４年会
  • Place of Presentation: 熊本大学（熊本県）
  • Year and Date: 20140327-20140330
• [Presentation] Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multi-drug resistant protein without cox inhibitory activity (2013)
  • Author(s): Mitsuhiro ARISAWA
  • Organizer: Asian Federation for Pharmaceutical Sciences Conference
  • Place of Presentation: Ramada Plaza Jeju Hotel（韓国）
  • Year and Date: 20131120-20131122
  • Invited
• [Presentation] ペプチド性天然物ベラクトシン A をプロトタイプとする高活性非ペプチド性プロテアソーム 阻害剤の創製:“Scaffold Hopping” に基づく論理的分子設計と合成 (2013)
  • Author(s): 川村周平
  • Organizer: 第39回反応と合成の進歩シンポジウム
  • Place of Presentation: 九州大学医学部百年講堂（福岡県）
  • Year and Date: 20131105-20131106
• [Presentation] 光学活性第三級ヨードシクロプロパンとニッケル触媒を用いた鈴木－宮浦カップリング反応の開発 (2013)
  • Author(s): 四辻慶佑
  • Organizer: 第43回複素環化学討論会
  • Place of Presentation: 長良川国際会議場（岐阜県）
  • Year and Date: 20131017-20131019
• [Presentation] 硫黄修飾金に担持したパラジウム触媒によるリ ガンドフリー条件でのダブルカルボニル化反応の開発 (2013)
  • Author(s): 谷口 敬寿
  • Organizer: 第 60 回 有機金属化学討論会
  • Place of Presentation: 学習院大学（東京都）
  • Year and Date: 20130912-20130914
• [Presentation] Development of sulfur-modified Au-supported palladium and its use in medicinal research (2013)
  • Author(s): Koji TAKAGI
  • Organizer: The Sixteenth International Symposium on Relations between Homogeneous and Heterogeneous Catalysis (ISHHC-16)
  • Place of Presentation: Hokkaido University（北海道）
  • Year and Date: 20130804-20130809
• [Presentation] One-pot Ring-closing Metathesis (RCM)/1,3-Dipolar Cycloaddition by an Assisted Tandem Ruthenium Catalysis for the Synthesis of Pyrrolo[1,2-a]quinolines (2013)
  • Author(s): Mitsuhiro ARISAWA
  • Organizer: 17th International Symposium on Organometallic Chemistry directed toward Organic Synthesis
  • Place of Presentation: Colorado State University（米国）
  • Year and Date: 20130728-20130801
• [Presentation] Palladium(0)-catalyzed Regioselective Intermolecular Direct Arylation of Tertiary Carbon on Cyclopropane (2013)
  • Author(s): Naoyuki HOSHIYA
  • Organizer: 17th International Symposium on Organometallic Chemistry directed toward Organic Synthesis
  • Place of Presentation: Colorado State University（米国）
  • Year and Date: 20130728-20130801
• [Presentation] Sulfur-modified Au-supported Palladium-catalyzed Double Carbonylation Reaction under Ligand-Free Conditions (2013)
  • Author(s): Takahisa TANIGUCHI
  • Organizer: 17th International Symposium on Organometallic Chemistry directed toward Organic Synthesis
  • Place of Presentation: Colorado State University（米国）
  • Year and Date: 20130728-20130801
• [Presentation] One-pot Ring-closing Metathesis (RCM)/1,3-Dipolar Cycloaddition by an Assisted Tandem Ruthenium Catalysis for the Synthesis of Pyrrolo[1,2-a]quinolines (2013)
  • Author(s): Mitsuhiro ARISAWA
  • Organizer: The 3rd International Symposium on Molecular Activation
  • Place of Presentation: Sheraton Steamboat Resort（米国）
  • Year and Date: 20130726-20130728
  • Invited
• [Presentation] Transition-Metal Nanosazied Palladium Particles for Organic Reaction (2013)
  • Author(s): Naoyuki HOSHIYA
  • Organizer: The 3rd International Symposium on Molecular Activation
  • Place of Presentation: Sheraton Steamboat Resort（米国）
  • Year and Date: 20130726-20130728
• [Presentation] One-pot Ring-Closing Metathesis (RCM)/1,3-Dipolar Cycloaddition by an Assisted Tandem Ruthenium Catalysis for the Synthesis of an ISonidolo[2,1-a]quinoline Structure Dye (2013)
  • Author(s): Mitsuhiro ARISAWA
  • Organizer: International Symposium on Olefin Metathesis and Related Chemistry
  • Place of Presentation: Todaiji-temple Lecture Hall（奈良県）
  • Year and Date: 20130714-20130719
• [Presentation] 疎水性相互作用に基づく機能性核酸の開発 (2013)
  • Author(s): 遠藤秀幸
  • Organizer: 日本薬学会北海道支部第140年会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 20130518-20130519
• [Presentation] クロスカップリング反応による芳香環直結型光学活性三置換シクロプロパンの合成
  • Author(s): 四辻 慶佑
  • Organizer: 25周年記念 万有札幌シンポジウム 未来を拓く創造有機化学
  • Place of Presentation: 北海道大学工学部オープンホール（北海道）
• [Patent(Industrial Property Rights)] 触媒金属ナノ粒子含有複合体及びその利用 (2014)
  • Inventor(s): 有澤光弘，周東智，星谷尚亨，新井聡史
  • Industrial Property Rights Holder: 有澤光弘，周東智，星谷尚亨，新井聡史
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2014/59312
  • Filing Date: 2014-03-28
  • Overseas