Development of environmentally friendly organometallic synthetic method for nitrogen containing heterocycles and its application to drug discovery

• Project/Area Number: 21790003
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: ARISAWA Mitsuhiro Hokkaido University, 大学院・薬学研究院, 准教授 (40312962)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 有機化学 / 合成化学 / 創薬科学 / 触媒・化学プロセス / 環境技術 / 触媒・化学フロセス

Research Abstract

Development of novel catalyst, reaction, and synthetic method for drug discovery was succeeded. Thus, sulfur-modified Au-supported Pd, ring-closing metathisis/oxidation, and cycloisomerization of ene and 1,3-diene were developed for drug library synthesis and discovery of selective MAO inhibitory agents.

Research Products

• [Journal Article] The Actual Active Species of the Sulfur-modified Gold-supported Palladium as a Highly Effective Palladium Reservoir in the Suzuki-Miyaura Coupling (2011)
  • Author(s): Naoyuki Hoshiya, Satoshi Shuto, Mitsuhiro Arisawa
  • Journal Title: Adv.Synth.Cat. 353 Pages: 743-748
  • Peer Reviewed
• [Journal Article] Alkene isomerization/enamide-ene and diene metathesis for the construction of indoles, quinolines, benzofurans and chromenes with a chiral cyclopropane substituent (2011)
  • Author(s): Takaaki Kobayashi
  • Journal Title: Org.Bio.Chem. Volume: 9 Pages: 1219-1224
  • Peer Reviewed
• [Journal Article] The Actual Active Species of the Sulfur-modified Gold-supported Palladium as a Highly Effective Palladium Reservoir in the Suzuki-Miyaura Coupling (2011)
  • Author(s): Naoyuki HOSHIYA
  • Journal Title: Adv.Synth.Cat Volume: 353 Pages: 743-748
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Conformationally Restricted Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cyclooxygenase Inhibitory Activity (2011)
  • Author(s): Mitsuhiro ARISAWA
  • Journal Title: ACS Med.Chem.Lett. Volume: 2(印刷中)
  • Peer Reviewed
• [Journal Article] Alkene isomerization/enamide-ene and diene metathesis for the construction of indoles, quinolines, benzofurans and chromenes with a chiral cyclopropane substituent (2010)
  • Author(s): Takaaki Kobayashi, Mitsuhiro Arisawa, Satoshi Shuto
  • Journal Title: Org.Bio.Chem. 9 Pages: 1219-1224
  • Peer Reviewed
• [Journal Article] Design and synthesis of indole derivatives of adenophostin A. A entry into subtype-selective IP3 receptor ligands (2010)
  • Author(s): Tetsuya Mochizuki, Akihiko Tanimura, Akihiro Nezu, Mika Ito, Hiroshi Abe, Yoshihiro Ito, Mitsuhiro Arisawa, Satoshi Shuto
  • Journal Title: Tetrahedron Lett. 51 Pages: 977-979
  • Peer Reviewed
• [Journal Article] Structure determination of Pd-catalyst supported on S-terminated GaAs(001) using DFT calculation (2010)
  • Author(s): Akira Ishii, Hiroki Asano, Mami Yokoyama, Shiro Tsukamoto, Satoshi Shuto, Mitsuhiro Arisawa
  • Journal Title: Physica Status Solidi C : Current Topics in Solid State Physics 7 Pages: 359-361
  • Peer Reviewed
• [Journal Article] Investigation of the Bioactive Conformation of Histamine H3 Receptor Antagonists by the Cyclopropylic Strain-Based Conformational Restriction Strategy (2010)
  • Author(s): Mizuki Watanabe, Takatsugu Hirokawa, Takaaki Kobayashi, Akira Yoshida, Yoshihiko Ito, Shizuo Yamada, Naoki Orimoto, Yasundo Yamasaki, Mitsuhiro Arisawa, Satoshi Shuto
  • Journal Title: J.Med.Chem. 53 Pages: 3585-3593
  • Peer Reviewed
• [Journal Article] Sulfur Modification of Au via Treatment with Piranha Solution Provides Low-Pd Releasing and Recyclable Pd Material, SAPd (2010)
  • Author(s): Naoyuki Hoshiya, Masahiko Shimoda, Hideki Yoshikawa, Yoshiyuki Yamashita, Satoshi Shuto, Mitsuhiro Arisawa
  • Journal Title: J.Am.Chem.Soc. 132 Pages: 7270-7272
  • Peer Reviewed
• [Journal Article] Hard X-ray Photoemission Spectroscopic Investigation of Palladium Catalysts immobilized on a GaAs(001) Surface (2010)
  • Author(s): Masahiko Shimoda, Tomoya Konishi, Kazuishi Tateishi, Takuya Toujyou, Shiro Tsukamoto, Nagatoshi Nishiwaki, Mitsuhiro Arisawa, Naoyuki Hoshiya, Satoshi Shuto, Nobuhiro Isomura, Hiroshi Yokota, Yuzo Furukawa, Kanji Iizuka, Tadashi Ogiwara, Yosuke Isozaki, Yoshiyuki Yamashita, Hideki Yoshikawa, Shigeru Ueda, Kazuto Kobayashi
  • Journal Title: J.Appl.Phy. 108
  • Peer Reviewed
• [Journal Article] Structure determination of Pd-catalyst supported on S-terminated GaAs(001) using DFT calculation (2010)
  • Author(s): Akira ISHII
  • Journal Title: Physica Status Solidi C : Current Topics in Solid State Physics Volume: 7 Pages: 359-361
  • Peer Reviewed
• [Journal Article] Design and synthesis of indole derivatives of adenophostin A. A entry into subtype-selective IP3 receptor ligands (2010)
  • Author(s): Tetsuya MOCHIZUKI
  • Journal Title: Tetrahedron Lett. Volume: 51 Pages: 977-979
  • Peer Reviewed
• [Journal Article] Investigation of the Bioactive Conformation of Histamine H3 Receptor Antagonists by the Cyclopropylic Strain-Based Conformational Restriction Strategy (2010)
  • Author(s): Mizuki WATANABE
  • Journal Title: J.Med.Chem Volume: 53 Pages: 3585-3593
  • Peer Reviewed
• [Journal Article] Sulfur Modification of Au via Treatment with Piranha Solution Provides Low-Pd Releasing and Recyclable Pd Material, SAPd (2010)
  • Author(s): Naoyuki HOSHIYA
  • Journal Title: J.Am.Chem.Soc. Volume: 132 Pages: 7270-7272
  • Peer Reviewed
• [Journal Article] Alantrypinone and its Derivatives : Synthesis and Antagonisti Activity toward Insect GABA Receptors (2009)
  • Author(s): Takayuki Watanabe, Mitsuhiro Arisawa, Kenji Narusuye, Mohammad S.Alam, Kazumi Yamamoto, Masaaki Mitomi, Yoshihisa Ozoe, Atsushi Nishida
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 94-110
  • Peer Reviewed
• [Journal Article] Three-dimensional structure-activity relationship study of belactosin A and its stereo- and regioisomers : development of potent proteasome inhibitors by a stereochemical diversity-oriented strategy. (2009)
  • Author(s): Keisuke Yoshida, Kazuya Yamaguchi, Akira Mizuno, Yuka Unno, Akira Asai, Takayuki Sone, Hideyoshi Yokosawa, Akira Matsuda, Mitsuhiro Arisawa, Satoshi Shuto
  • Journal Title: Org.Bioorg.Chem. 7 Pages: 1868-1877
  • Peer Reviewed
• [Journal Article] Development of Recyclabe and Low-leaching Palladium Catalyst Supported on Sulfur-modified Gallium Arsenide (001) plate for Use in Suzuki-Miyaura Coupling (2009)
  • Author(s): Naoyuki Hoshiya, Nobuhiko Isomura, Masahiko Shimoda, Hideki Yoshikawa, Yoshiyuki Yamashita, Kanji Iizuka, Shiro Tsukamoto, Satoshi Shuto, Mitsuhiro Arisawa
  • Journal Title: Chem Cat Chem 1 Pages: 279-285
  • Peer Reviewed
• [Journal Article] Aromatic Enamide-Ene Metathesis toward Substituted Indoles and its Application to the Synthesis of Indomethacins (2009)
  • Author(s): Yayoi Kasaya, Kosuke Hoshi, Yukiyoshi Terada, Atsushi Nishida, Satoshi Shuto, Mitsuhiro Arisawa
  • Journal Title: Eur.J.Org.Chem. Pages: 4606-4613
  • Peer Reviewed
• [Journal Article] Development of recyclable and environmentally benign palladium catalyst supported on sulfur-terminated gallium arsenide(001)for use in Suzuki-Miyaura coupling (2009)
  • Author(s): Naoyuki HOSHIYA
  • Journal Title: ChemCatChem 1 Pages: 279-285
  • Peer Reviewed
• [Journal Article] Aromatic enamide-ene metathesis toward substituted indoles and its application to the synthesis of indomethacin (2009)
  • Author(s): Yayoi KASAYA
  • Journal Title: European Journal of Organic Chemistry Pages: 4606-4613
  • Peer Reviewed
• [Journal Article] Three-dimensional structure-activity relationship study of belactosin A and its stereo- and regioisomers : development of potent proteasome inhibitors by the stereochemical diversity-oriented strategy (2009)
  • Author(s): Keisuke YOSHIDA
  • Journal Title: Organic & Bioorganic Chemistry 7 Pages: 1868-1877
  • Peer Reviewed
• [Journal Article] Alantrypinone and its derivatives and Synthesis and antagonist activity toward insect GABA receptors (2009)
  • Author(s): Takayuki WATANABE
  • Journal Title: Bioorganic & Medicinal Chemistry 17 Pages: 94-110
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Conformationally Restricted Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cyclooxygenase Inhibitory Activity
  • Author(s): Mitsuhiro Arisawa, Yayoi Kasaya, Tohru Obata, Takuma Sasaki, Mika Ito, Hiroshi Abe, Yoshihiro Ito, Akihito Yamano, Satoshi Shuto
  • Journal Title: ACS Med.Chem.Lett. in press
  • Peer Reviewed
• [Presentation] Development of environmentally friendly organometallic catalysis for drug discovery (2011)
  • Author(s): 有澤光弘
  • Organizer: 2010年アメリカ化学会秋季大会
  • Place of Presentation: ボストンコンベンションセンター、米国ボストン
  • Year and Date: 2011-08-24
• [Presentation] Enamide-ene metathesis for constructing chiral 2-cyclopropylheterocycles : Indole, quinoline, benzofuran and chromene (2011)
  • Author(s): 小林高明
  • Organizer: 2010年アメリカ化学会秋季大会
  • Place of Presentation: ボストンコンベンションセンター、米国ボストン
  • Year and Date: 2011-08-24
• [Presentation] 制がん性プロテアソーム阻害剤ベラクトシンAシス形立体異性体の構造活性相関研究 (2011)
  • Author(s): 川村周平
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡、静岡市
  • Year and Date: 2011-03-31
• [Presentation] β-C-グルコシド型イノシトールリン脂質ミミックの設計と合成 (2011)
  • Author(s): 大浦泰
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡、静岡市
  • Year and Date: 2011-03-31
• [Presentation] 光学活性ブロモメチレンシクロプロパンを用いる鈴木-宮浦クロスカップリング反応 (2011)
  • Author(s): 田辺真人
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: グランシップ、静岡市
  • Year and Date: 2011-03-29
• [Presentation] 4"-分枝型サイクリックADPカーボサイクリックリボースの合成研究 (2010)
  • Author(s): 佐藤隆俊
  • Organizer: 日本薬学会北海道支部第135回例会
  • Place of Presentation: 北海道大学学術交流会館、札幌市
  • Year and Date: 2010-11-27
• [Presentation] 硫黄就職した金に担持した高性能パラジウム触媒-SAPd-の開発と三次元多様型創薬ライブラリー構築への展開 (2010)
  • Author(s): 有澤光弘
  • Organizer: 第36回反応と合成の進歩シンポジウム
  • Place of Presentation: ウインク愛知、名古屋市
  • Year and Date: 2010-11-02
• [Presentation] 硫黄就職した金に担持した高性能パラジウム触媒-SAPd-の開発と三次完多様型創薬ライブラリー構築への展開 (2010)
  • Author(s): 有澤光弘
  • Organizer: 第36回反応と合成の進歩シンポジウム
  • Place of Presentation: ウインク愛知、名古屋市
  • Year and Date: 2010-11-02
• [Presentation] インドールアルカロイド、シンコナミノンおよびその類縁体の合成研究:ジエンとオレフィンの環化異性化反応 (2010)
  • Author(s): 小川貴大
  • Organizer: 第40回複素環化学討論会
  • Place of Presentation: 仙台市民会館、仙台市
  • Year and Date: 2010-10-14
• [Presentation] 液層コンビナトリアル合成用硫黄修飾金担持型パラジウムの開発:繰返し利用と低漏洩 (2010)
  • Author(s): 新井聡史
  • Organizer: 第57回有機金属化学討論会
  • Place of Presentation: 第57回有機金属化学討論会
  • Year and Date: 2010-09-18
• [Presentation] 液層コンビナトリアル合成用硫黄修飾金担持型パラジウムの関発:繰返し利用と低漏洩 (2010)
  • Author(s): 新井聡史
  • Organizer: 第57回有機金属化学討論会
  • Place of Presentation: 第57回有機金属化学討論会
  • Year and Date: 2010-09-18
• [Presentation] Development of environmentally friendly organometallic catalysis for drug discovery (2010)
  • Author(s): 有澤光弘
  • Organizer: 2010年アメリカ化学会秋季大会
  • Place of Presentation: ボストンコンベンションセンター、米国ボストン(招待講演)
  • Year and Date: 2010-08-24
• [Presentation] 機能性分子合成用硫黄修飾金担持型Pd(SAPd)の開発 (2010)
  • Author(s): 有澤光弘
  • Organizer: 環境に優しい材料の為の融合領域研究会
  • Place of Presentation: 鳥取大学、鳥取市
  • Year and Date: 2010-08-04
• [Presentation] 機能性分子合成用硫黄修飾金担持型Pd(SAPd)の開発 (2010)
  • Author(s): 有澤光弘
  • Organizer: 環境に優しい材料の為の融合領域研究会
  • Place of Presentation: 鳥取大学、鳥取市(招待講演)
  • Year and Date: 2010-08-04
• [Presentation] 環化異性化反応を鍵反応としたシンコナミノン及び類縁体の合成研究 (2010)
  • Author(s): 小川貴大
  • Organizer: 第22回万有札幌シンポジウム
  • Place of Presentation: 札幌芸術文化の館、札幌市
  • Year and Date: 2010-07-03
• [Presentation] 機能性分子合成用硫黄修飾金担持型パラジウムの開発 (2010)
  • Author(s): 星谷尚亨
  • Organizer: 第8回次世代を担う有機化学シンポジウム
  • Place of Presentation: 日本薬学会長井記念ホール、東京都渋谷区
  • Year and Date: 2010-05-13
• [Presentation] Grubbs触媒を用いたRing-closing metathesis (RCM)-酸化ワンポット反応による2-キノロン誘導体新規合成法の開発 (2010)
  • Author(s): 加藤宏茂
  • Organizer: 日本薬学会北海道支部第134回例会
  • Place of Presentation: 札幌コンベンションセンター、札幌市
  • Year and Date: 2010-05-08
• [Presentation] Grubbs触媒を用いたRing-closing metathesis(RCM)-酸化ワンポット反応による2-キノロン誘導体新規合成法の開発 (2010)
  • Author(s): 加藤宏茂
  • Organizer: 日本薬学会北海道支部第134回例会
  • Place of Presentation: 札幌コンベンションセンター、札幌市
  • Year and Date: 2010-05-08
• [Presentation] 8-置換サイクリックADP-4-チオリボースの合成及び生物活性 (2010)
  • Author(s): 高野智史
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学津島キャンパス、岡山市
  • Year and Date: 2010-03-28
• [Presentation] 三次元構造的多様性を鍵とするGABAトランスポーターサブタイプ選択的リガンドの設計と合成 (2010)
  • Author(s): 中田和彰
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学津島キャンパス、岡山市
  • Year and Date: 2010-03-28
• [Presentation] アイソザイム選択的COX阻害剤の開発を目的とする配座制御型インドメタシン類縁体の合成と薬理活性 (2010)
  • Author(s): 笠谷弥生
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学津島キャンパス、岡山市
  • Year and Date: 2010-03-28
• [Presentation] 光学活性シクロプロパンを有する複素環化合物合成法の開発 (2010)
  • Author(s): 小林高明
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学津島キャンパス、岡山市
  • Year and Date: 2010-03-28
• [Presentation] 創薬用低分子化合物ライブラリー構築を指向した硫黄修飾金担持型パラジウムの開発 (2009)
  • Author(s): 星谷尚亨
  • Organizer: 第133回日本薬学会北海道支部例会
  • Place of Presentation: 北海道医療大学札幌サテライトキャンパス、札幌市
  • Year and Date: 2009-11-28
• [Presentation] サブタイプ選択的COX阻害剤の開発を目的とする配座制御型インドメタシン類縁隊の設計・合成及び配座解析 (2009)
  • Author(s): 笠谷弥生
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京大学安田講堂、東京都文京区
  • Year and Date: 2009-11-25
• [Presentation] シクロプロパン歪みに基づくヒスタミンH3受容体リガンドの設計と活性配座解析 (2009)
  • Author(s): 小林高明
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京大学安田講堂、東京都文京区
  • Year and Date: 2009-11-25
• [Presentation] サブタイブ選択的COX阻害剤の開発を目的とする配座制御型インドメタシン類縁隊の設計・合成及び配座解析 (2009)
  • Author(s): 笠谷弥生
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京大学安田講堂、東京都文京区
  • Year and Date: 2009-11-25
• [Presentation] 強力な細胞内Ca2+放出活性を有するサイクリックcADPtRの設計と合成 (2009)
  • Author(s): 有澤光弘
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢市文化ホール、金沢市
  • Year and Date: 2009-11-16
• [Presentation] Recyclable and environmentally friendly palladium catalyst supported on sulfur-modified metal surface (2009)
  • Author(s): 星谷尚亨
  • Organizer: 第56回有機金属化学討論会
  • Place of Presentation: 同志社大学、京都市
  • Year and Date: 2009-09-11
• [Presentation] Synthesis of 2-quinolone derivatives : ring-closing metathesis (RCM)-oxidation tandem reaction, by Grubbs catalyst (2009)
  • Author(s): 加藤宏茂
  • Organizer: 第56回有機金属化学討論会
  • Place of Presentation: 同志社大学、京都市
  • Year and Date: 2009-09-10
• [Presentation] Synthesis of 2-quinolone derivatives : ring-closing metathesis(RCM)-oxidation tandem reaction, by Grubbs catalyst (2009)
  • Author(s): 加藤宏茂
  • Organizer: 第56回有機金属化学討論会
  • Place of Presentation: 同志社大学、京都市
  • Year and Date: 2009-09-10
• [Presentation] 立体多様性を鍵とするシクロプロパン型ペプチドミメティックーメラノコルチンリガンドの創製研究 (2009)
  • Author(s): 水野彰
  • Organizer: 第7回次世代を担う有機化学シンポジウム
  • Place of Presentation: 大阪大学コンベンションセンターMOホール、吹田市
  • Year and Date: 2009-07-24
• [Remarks] ホームページ
  • URL: http://www.pharm.hokudai.ac.jp/yuuki/index.html
• [Patent(Industrial Property Rights)] Gold-based catalyst precursors, their manufacture, their uses in mesh form, and reactors employing the same (2010)
  • Inventor(s): 有澤光弘, 周東智, 星谷尚亨
  • Industrial Property Rights Holder: National University Corporation Hokkaido University, Japan ; Furuya Metal Co., Ltd
  • Filing Date: 2010-07-27
• [Patent(Industrial Property Rights)] Gold-based catalyst precursors, their manufacture, their uses in mesh form, and reactors employing the same (2010)
  • Inventor(s): Arisawa, Mitsuhiro ; Shuto, Satoshi ; Hoshiya, Naoyuki
  • Industrial Property Rights Holder: National University Corporation Hokkaido University, Japan ; Furuya Metal Co., Ltd.
  • Filing Date: 2010-07-27
  • Overseas
• [Patent(Industrial Property Rights)] 触媒前駆体、その製造方法、その使用方法、及びそれを用いたリアクター (2009)
  • Inventor(s): 有澤光弘、周東智、星谷尚亨
  • Industrial Property Rights Holder: 北海道大学・(株)フルヤ金属
  • Filing Date: 2009-07-21
• [Patent(Industrial Property Rights)] 触媒前駆体、その製造方法、その使用方法、及びそれを用いたリアクター (2009)
  • Inventor(s): 有澤光弘、周東智、星谷尚亨
  • Industrial Property Rights Holder: 北海道大学・(株)フルヤ金属
  • Industrial Property Number: 2009-170507
  • Filing Date: 2009-07-21