Development of Catalytic Asymmetric Reactions for the Construction of Stereogenic Tetrasubstituted Carbon with 100% Atom-efficiency and Its Application to the Reactions with Allosteric Regulation

• Project/Area Number: 19790008
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: KUMAGAI Naoya The University of Tokyo, 大学院薬学系研究科, 助教 (40431887)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 不斉触媒 / 4 置換炭素 / 原子効率 / アロステリック制御 / 有機化学 / アリルシアニド / 希土類金属 / プロトン移動 / 不斉4置換炭素 / 動的構造変化 / ソフト金属 / 多機能触媒 / 4置換炭素 / ニトロアルドール反応 / アミノ化反応 / マンニッヒ型反応 / 希土類

Research Abstract

新規触媒の創製により、原子効率100%の不斉4 置換炭素構築型反応の開発に成功し、医薬品の環境調和型短工程合成の有力な手法となることを示した。

Research Products

• [Journal Article] Linking Structural Dynamics and Functional Diversity in Asymmetric Catalysis (2009)
  • Author(s): Akihiro Nojiri, Naoya Kumagai, Masakatsu Shibasaki
  • Journal Title: J. Am. Chem. Soc. 131 Pages: 3779-3784
  • Peer Reviewed
• [Journal Article] Direct Catalytic Asymmetric Addition of Allyl Cyanide to Ketones (2009)
  • Author(s): Ryo Yazaki, Naoya Kumagai, Masakatsu Shibasaki
  • Journal Title: J. Am. Chem. Soc. 131 Pages: 3195-3197
  • Peer Reviewed
• [Journal Article] Direct Catalytic Asymmetric Addition of Allyl Cyanide to Ketones (2009)
  • Author(s): Ryo Yazaki
  • Journal Title: Journal of the American Chemical Society 131 Pages: 3195-3197
  • Peer Reviewed
• [Journal Article] Linking Structural Dynamics and Functional Diversity in Asymmetric Catalysis (2009)
  • Author(s): Akihiro Nojiri
  • Journal Title: Journal of the American Chemical Society 131 Pages: 3779-3784
  • Peer Reviewed
• [Journal Article] Direct Catalytic Asymmetric Addition of Allylic Cyanides to Ketoimines (2008)
  • Author(s): Ryo Yazaki, Tatsuya Nitabaru, Naoya Kumagai, Masakatsu Shibasaki
  • Journal Title: J. Am. Chem. Soc. 130 Pages: 14477-14479
  • Peer Reviewed
• [Journal Article] Asymmetric Catalysis via Dynamic Substrate/Ligand Rare Earth Metal Conglomerate (2008)
  • Author(s): Akihiro Nojiri, Naoya Kumagai, Masakatsu Shibasaki
  • Journal Title: J. Am. Chem. Soc. 130 Pages: 5630-5631
  • Peer Reviewed
• [Journal Article] Asymmetric Catalysis via Dynamic Substrate/Ligand Rare Earth Metal Conglomerate (2008)
  • Author(s): Akihiro Nojiri
  • Journal Title: Journal of the American Chemical Society 130 Pages: 5630-5631
  • Peer Reviewed
• [Journal Article] Strategies for Constructing Diverse Chiral Environments in Multimetallic Bifunctional Asymmetric Catalysis (2008)
  • Author(s): Masakatsu Shibasaki
  • Journal Title: Synlett Pages: 1583-1602
  • Peer Reviewed
• [Journal Article] An Improved Lanthanum Catalytic System for Asymmetric Amination; Toward a Practical Asymmetric Synthesis of AS-3201(Ranirestat) (2008)
  • Author(s): Tomoyuki Mashiko
  • Journal Title: Organic Letters 10 Pages: 2725-2728
  • Peer Reviewed
• [Journal Article] Direct Catalytic Asymmetric Addition of Allylic Cyanides to Ketoimine (2008)
  • Author(s): Ryo Yazaki
  • Journal Title: Journal of the American Chemical Society 130 Pages: 14477-14479
  • Peer Reviewed
• [Journal Article] A Catalytic Asymmetric anti-Selective Nitroaldol Reaction with a Neodymium Sodium Heterobimetallic Complex (2008)
  • Author(s): Tatsuya Nitabaru
  • Journal Title: Tetrahedron Letters 49 Pages: 272-275
  • Peer Reviewed
• [Journal Article] En Route to an Efficient Asymmetric Synthesis of AS-3201 (2007)
  • Author(s): Tomoyuki Mashiko, Keiichi Hara, Daisuke Tanaka, Yuji Fujiwara, Naoya Kumagai, Masakatsu Shibasaki
  • Journal Title: J. Am. Chem. Soc. 129 Pages: 11342-11343
  • Peer Reviewed
• [Journal Article] Catalytic Nucleophilic Activation of Acetonitrile via a Cooperative Catalysis of Cationc Ru Complex, DBU, and NaPF_6. (2007)
  • Author(s): Naoya Kumagai
  • Journal Title: Tetrahedron 63 Pages: 8598-8608
  • Peer Reviewed
• [Journal Article] En Route to an Efficient Catalytic Asymmetric Synthesis of AS-3201. (2007)
  • Author(s): Tomoyuki Mashiko
  • Journal Title: Journal of the American Chemical Society 129 Pages: 11342-11343
  • Peer Reviewed
• [Presentation] アリリックシアニドのケトンへの触媒的不斉付加反応 (2009)
  • Author(s): 熊谷直哉
  • Organizer: 第129回日本薬学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-03-26
• [Presentation] ジアステレオスイッチングを示す希土類・アミド錯体 : 触媒的不斉Mannich型反応による不斉4級炭素構築 (2008)
  • Author(s): 熊谷直哉
  • Organizer: 第94回有機合成シンポジウム
  • Place of Presentation: 早稲田大学国際会議場
  • Year and Date: 2008-11-07
• [Presentation] Mannich-type Reaction with Amide Ligand/Rare Earth Metal Complexes (2008)
  • Author(s): Naoya Kumagai, Masakatsu Shibasaki
  • Organizer: Dynamic Nature of the Catalyst Complex and Stereochemical Diversity 5th Balticum Organicum Syntheticum
  • Place of Presentation: Lithuania IMS Univ.
  • Year and Date: 2008-07-02
• [Presentation] Mannich-type Reaction with Amide Ligand/Rare 'Earth Metal Complexes: Dynamic Nature of the Catalyst Complex and Stereochemical Diversity (2008)
  • Author(s): Naoya Kumagai
  • Organizer: 5_<th> Balticum Organicum Syntheticum
  • Place of Presentation: Lithuania IMS Univ
  • Year and Date: 2008-07-02
• [Presentation] Scアミド錯体による触媒的不斉Mannich型反応 (2008)
  • Author(s): 野尻明宏
  • Organizer: 日本薬学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-03-27
• [Presentation] 新規ランタノイドーアミド錯体を用いた触媒的不斉アミノ化反応の開発とAS-3201(ranirestat)の不斉合成への展開 (2007)
  • Author(s): 熊谷直哉
  • Organizer: 第33回反応と合成の進歩シンポジウム
  • Place of Presentation: 長崎ブリックホール
  • Year and Date: 2007-11-05
• [Presentation] Catalytic Nucleophilic Activation of Acetonitrile via a Cooperative Catalysis of Cationic Ru Complex, DBU, and NaPF6. (2007)
  • Author(s): Naoya Kumagai and Masakatsu Shibasaki
  • Organizer: 40th NOS
  • Place of Presentation: Duke Univ., NC, USA
  • Year and Date: 2007-07-06
• [Presentation] Catalytic Nucleophilic Activation of Acetonitrile via a Cooperative Catalysis of Cationic Ru Complex, DBU, and NaPF_6. (2007)
  • Author(s): Naoya Kumagai
  • Organizer: 40th NOS
  • Place of Presentation: Duke Univ., NC, USA
  • Year and Date: 2007-07-06
• [Book] Acid Catalysis in Modern Organic Synthesis (2008)
  • Author(s): Masakatsu Shibasaki, Shigeki Matsunaga, Naoya Kumagai
  • Publisher: Wiley-VCH
• [Book] Acid Catalysis in Modern Organic Synthesis (chapter 13) (2008)
  • Author(s): Masakatsu Shibasaki
  • Total Pages: 85
  • Publisher: Wiley-VCH
• [Remarks] 薬事日報 掲載2008年12月
• [Remarks] 日本経済新聞 掲載2007年5月4日
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jprkanai/~kanai/index.html
• [Patent(Industrial Property Rights)] 立体選択的不斉ニトロアルドール反応用触媒 (2009)
  • Inventor(s): 二田原達也、熊谷直哉、柴崎正勝
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2009-01-26
• [Patent(Industrial Property Rights)] 不斉アミノ化反応用触媒 (2008)
  • Inventor(s): 柴崎正勝, 熊谷直哉, 益子智之
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2008-02-13
• [Patent(Industrial Property Rights)] 斉アミノ化反応用触媒 (2008)
  • Inventor(s): 柴崎正勝、熊谷直哉、益子智之
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2008-02-13
• [Patent(Industrial Property Rights)] 立体選択的不斉ニトロアルドール反応用触媒 (2007)
  • Inventor(s): 柴崎正勝, 熊谷直哉, 二田原達也
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2007-11-01
• [Patent(Industrial Property Rights)] 不斉アミノ化反応用触媒 (2007)
  • Inventor(s): 柴崎正勝、熊谷直哉、益子智之
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2007-04-20
• [Patent(Industrial Property Rights)] 立体選択的不斉ニトロアルドール反応用触媒 (2007)
  • Inventor(s): 柴崎正勝、熊谷直哉、二田原達也
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2007-11-01