Development of Organic Reactions Using New 1,4-Zwitterionic Intermediates

• Project/Area Number: 24590007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: MATSUO Junichi 金沢大学, 薬学系, 教授 (50328580)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 有機化学 / 有機合成 / 有機合成化学 / 全合成 / 付加環化 / ルイス酸

Outline of Final Research Achievements

We found that 1,4-zwitterionic intermediates which were formed by Lewis acid-mediated ring cleavage of 3-alkoxy or 3-aminocyclobutanones reacted with indoles at their C2-C3 double bonds to afford the corresponding hydrocarbazoles. We accomplished total synthesis of racemic aspidospermidine and synthesis of partial structure of racemic strictamine by using the above-mentioned cycloaddition reaction.
Furthermore, we accomplished optically active thromboxane B2 by using formal [4+2] cycloaddition reaction between a 3-alkoxycyclobutanone and an aldehyde.

Research Products

• [Journal Article] 1,4-Zwitterionic intermediates formed by cleavage of a cyclobutane ring and their cycloaddition reactions (2014)
  • Author(s): Jun-ichi Matsuo
  • Journal Title: Tetrahedron Letters Volume: 55 Issue: 16 Pages: 2589-2595
  • DOI: 10.1016/j.tetlet.2014.03.053
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reaction mechanism analysis by using kinetic isotope effect (2013)
  • Author(s): Jun-ichi Matsuo
  • Journal Title: Kagaku to Kyoiku Volume: 61 Pages: 244-247
  • Peer Reviewed
• [Journal Article] The Mukaiyama Aldol Reaction: 40 Years of Continuing Development (2013)
  • Author(s): Jun-ichi Matsuo* and Masahiro Murakami*
  • Journal Title: Angew. Chem. Int. Ed. Volume: 52 Issue: 35 Pages: 9109-9118
  • DOI: 10.1002/anie.201303192
  • Peer Reviewed
• [Journal Article] Chemoselective formal [4+2] cycloaddition of 3-hydroxycyclobutanones with enones (2013)
  • Author(s): Kosuke Harada, Aya Nowaki, and Jun-ichi Matsuo*
  • Journal Title: Asian J. Org. Chem. Volume: 2 Issue: 11 Pages: 923-926
  • DOI: 10.1002/ajoc.201300156
  • Peer Reviewed
• [Journal Article] Regioselective Inter- and Intramolecular Formal [4+2] Cycloaddition of Cyclobutanones to Indoles and Total Synthesis of (±)-Aspidospermidine (2013)
  • Author(s): Mizuki Kawano, Takaaki Kiuchi, Shoko Negishi, Hiroyuki Tanaka, Takaya Hoshikawa, Jun-ichi Matsuo,* and Hiroyuki Ishibashi
  • Journal Title: Angew. Chem. Int. Ed. Volume: 52 Issue: 3 Pages: 906-910
  • DOI: 10.1002/anie.201206734
  • Peer Reviewed
• [Journal Article] Formal [4+2] cycloaddition of cyclobutanones bearing alkyne-cobalt complex at their 3-positions (2012)
  • Author(s): Mizuki Kawano, Takaaki Kiuchi, Jun-ichi Matsuo, Hiroyuki Ishibashi
  • Journal Title: Tetrahedron Lett. Volume: 53 Issue: 4 Pages: 432-434
  • DOI: 10.1016/j.tetlet.2011.11.067
  • Peer Reviewed
• [Journal Article] Intramolecular [2+2] Cycloaddition of Homoallylketenes to Bicyclo[2.1.1]hexan-5-ones (2012)
  • Author(s): Takaya Hoshikawa, Kei Tanji, Jun-ichi Matsuo, Hiroyuki Ishibashi
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 60 Issue: 4 Pages: 548-553
  • DOI: 10.1248/cpb.60.548
  • NAID: 130001852448
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Journal Article] Indium (III) triflate-catalyzed reaction of 2-carbomethoxycyclobutanone with nitrones (2012)
  • Author(s): Jun-ichi Matsuo, Ryosuke Okuno, Hiroyuki Ishibashi
  • Journal Title: Tetrahedron Lett. Volume: 53 Issue: 17 Pages: 2257-2259
  • DOI: 10.1016/j.tetlet.2012.02.092
  • NAID: 120003959451
  • Peer Reviewed
• [Journal Article] Titanium(IV) Chloride-Mediated Ring Cleavage and Michael Addition of 3,3-Dialkylcyclobutanones and 3-[(Trimethylsilyl)methyl]-cyclobutanones (2012)
  • Author(s): Ryosuke Okuno, Jun-ichi Matsuo,* and Hiroyuki Ishibashi
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 60 Issue: 6 Pages: 793-797
  • DOI: 10.1248/cpb.60.793
  • NAID: 130001852483
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Presentation] Lewis acid-catalyzed Formal [4+2] Cycloaddition of Cyclobutanones (2015)
  • Author(s): Junichi Matsuo
  • Organizer: 2nd International Symposium on Catalysis Toward Green Sustainable Chemistry
  • Place of Presentation: University of Tokyo
  • Year and Date: 2015-03-30
  • Invited
• [Presentation] アゾ化合物と３－エトキシシクロブタノンとの形式的[4+2]環化付加反応 (2015)
  • Author(s): 嶋佑介、松尾淳一
  • Organizer: 日本薬学会第１３５年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] シクロブタノンを用いる環化付加反応の開発 (2015)
  • Author(s): 松尾淳一
  • Organizer: 創薬基盤化学研究第９回若手セミナー
  • Place of Presentation: 立命館大学
  • Year and Date: 2015-01-16
  • Invited
• [Presentation] New Synthetic Utility of beta-Silyl Ketones (2013)
  • Author(s): Jun-ichi Matsuo, Aya Nowaki, and Mizuki Kawano
  • Organizer: The 13th Tateshina Conference on Organic Chemistry
  • Place of Presentation: 蓼科フォーラム（長野県茅野市）
• [Presentation] トロンボキサンＢ２の全合成研究 (2013)
  • Author(s): 木内貴彬、松尾淳一
  • Organizer: 第４３回複素環討論会
  • Place of Presentation: 長良川国際会議場（岐阜県岐阜市）
• [Presentation] β―シリルケトンとアルデヒドとの反応によるβ,γ―不飽和ケトンの合成 (2013)
  • Author(s): 野脇綾、河野瑞貴、原田紘佑、松尾淳一
  • 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（福岡県福岡市）
• [Presentation] Synthesis of beta,gamma-unsaturated ketones from beta-silyl ketones and aldehydes (2013)
  • Author(s): Aya Nowaki, Mizuki Kawano, Kosuke Harada, Jun-ichi Matsuo
  • Organizer: 10th International Symposium on Carbanion Chemistry
  • Place of Presentation: 同支社大学（京都市上京区）
• [Presentation] Formal [4+2] cycloaddition of cyclobutanones and indoles: Total synthesis of (±)-aspidospermidine (2013)
  • Author(s): Jun-ichi Matsuo, Mizuki Kawano, Takaaki Kiuchi, Hiroyuki Ishibashi
  • Organizer: 14th Tetrahedron Symposium
  • Place of Presentation: ウィーン（オーストリア）
• [Presentation] シクロブタノンとインドールとの形式的環化付加によるアスピドスペルミジンの全合成 (2013)
  • Author(s): 松尾淳一・河野瑞貴・木内貴彬・石橋弘行
  • Organizer: 日本化学会第９３春季年会
  • Place of Presentation: 立命館大学くさつキャンパス（滋賀県）
• [Presentation] β－シリルケトンとアルデヒドとの反応による β,γ－不飽和ケトンの合成 (2013)
  • Author(s): 野脇 綾、河野 瑞貴、松尾 淳一、石橋 弘行
  • Organizer: 日本薬学会第１３３年会
  • Place of Presentation: 横浜（神奈川県）
• [Presentation] ThromboxaneB2の合成研究 (2013)
  • Author(s): 木内貴彬、松尾淳一、石橋弘行
  • Organizer: 日本薬学会第１３３年会
  • Place of Presentation: 横浜（神奈川県）
• [Presentation] シクロブタノン類のインドール誘導体への[4+2]環化付加反応の開発と(±)-Aspidospermidineの全合成 (2012)
  • Author(s): 河野 瑞貴，木内 貴彬，根岸 祥子，田中 宏幸，干川 貴也， 橋詰 未央，松尾 淳一，石橋 弘行
  • Organizer: 第３８回反応と合成の進歩シンポジウム
  • Place of Presentation: タワーホール船堀（千葉県）
• [Presentation] β－シリルケトンとアルデヒドとの反応 (2012)
  • Author(s): 野脇綾、松尾淳一、石橋弘行
  • Organizer: 日本薬学会北陸支部第１２４例会
  • Place of Presentation: 富山大学（富山県）
• [Presentation] [4+2]-Type Cycloadditions of 1,4-Zwitterionic Intermediates (2012)
  • Author(s): Junichi Matsuo, Mizuki Kawano, Ryohei Okado, Shun Sasaki, and Hiroyuki Ishibashi
  • Organizer: Tateshina Conference on Organic Chemistry
  • Place of Presentation: 蓼科（長野県）
• [Presentation] Formal [4+2] Cycloaddition of Cyclobutanones to Indoles and Total Synthesis of (±)-Aspidospermidine (2012)
  • Author(s): Mizuki Kawano, Takaaki Kiuchi, Shoko Negishi, Takaya Hoshikawa, Jun-ichi Matsuo, Hiroyuki Ishibashi
  • Organizer: The 6th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: Osaka（大阪府）
• [Remarks] 金沢大学 機能性分子設計学研究室ホームページ
  • URL: http://www.p.kanazawa-u.ac.jp/~gousei/