Development of gold-catalyzed synthetic reactions utilizing the properties revealed by theoretical calculations

• Project/Area Number: 18K06571
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: SAITO Tatsuo 東京農業大学, 生命科学部, 准教授 (40612065)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 金触媒 / ポリエーテル / 環化反応 / 金触媒反応 / DFT計算 / 天然物合成 / 創薬化学 / 機能性分子 / 理論化学 / 有機合成化学

Outline of Final Research Achievements

In this study, we have developed a short-step synthesis of heteroaromatic compounds based on the stabilization of unstable gold intermediates by proton sources. Furthermore, we revealed that the proton source is involved not only in the stabilization of vinyl gold intermediates but also in the reactivation of the gold catalyst from resting state.

Academic Significance and Societal Importance of the Research Achievements

医薬品、蛍光分子などの分子機能は構造などを精密に制御した効率的合成法に立脚しており、その背景にある元素レベル、分子レベルの設計が分子機能創出の鍵となっています。すなわち、機能創発を志向した反応設計、開発を基盤として未踏の分子機能の実現が可能となります。本研究では金の特性を最大限に活用することで、機能性分子のコアとして重要ながらその効率的合成が困難であった骨格群を標的に、生命科学、物質科学を切り拓く新物性、新機能の創出を狙います。

Research Products

• [Journal Article] Disproof of the Proposed Structures of Bradyoxetin, a Putative Bradyrhizobium japonicum Signaling Molecule, and HMCP, a Putative Ralstonia solanacearum Quorum-Sensing Molecule (2021)
  • Author(s): Yajima Arata、Katsuta Ryo、Shimura Mikaho、Yoshihara Ayaka、Saito Tatsuo、Ishigami Ken、Kai Kenji
  • Journal Title: Journal of Natural Products Volume: 84 Issue: 2 Pages: 495-502
  • DOI: 10.1021/acs.jnatprod.0c01369
  • Peer Reviewed
• [Journal Article] Synthesis and Determination of Absolute Configuration of Zealexin A1, a Sesquiterpenoid Phytoalexin from Zea mays (2021)
  • Author(s): Yajima Arata、Shimura Mikaho、Saito Tatsuo、Katsuta Ryo、Ishigami Ken、Huffaker Alisa、Schmelz Eric A.
  • Journal Title: European Journal of Organic Chemistry Volume: 2021 Issue: 7 Pages: 1174-1178
  • DOI: 10.1002/ejoc.202001596
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones (2019)
  • Author(s): Kamo Shogo、Saito Tatsuo、Kusakabe Yasuha、Tomoshige Shusuke、Uchiyama Masanobu、Tsubaki Kazunori、Kuramochi Kouji
  • Journal Title: The Journal of Organic Chemistry Volume: 84 Issue: 21 Pages: 13957-13966
  • DOI: 10.1021/acs.joc.9b02119
  • Peer Reviewed
• [Journal Article] Reaction Development Utilizing the Features of Chemical Elements and Synthesis of Marine Natural Products (2018)
  • Author(s): 斉藤竜男
  • Journal Title: YAKUGAKU ZASSHI Volume: 138 Issue: 11 Pages: 1335-1344
  • DOI: 10.1248/yakushi.18-00126
  • NAID: 130007502929
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2018-11-01
  • Peer Reviewed
• [Journal Article] Discovery of a Small Molecule to Increase Cardiomyocytes and Protect the Heart After Ischemic Injury (2018)
  • Author(s): Hara H, Takeda N, Kondo M, Kubota M, Saito T, Maruyama J, Fujiwara T, Maemura S, Ito M, Naito AT, Harada M, Toko H, Nomura S, Kumagai H, Ikeda Y, Ueno H, Takimoto E, Akazawa H, Morita H, Aburatani H, Hata Y, Uchiyama M, Komuro I.
  • Journal Title: JACC: Basic to Translational Science Volume: 3 Issue: 5 Pages: 639-653
  • DOI: 10.1016/j.jacbts.2018.07.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Direct synthesis of aryl-annulated [c]carbazoles by gold(I)-catalysed cascade reaction of azide-diynes and arenes (2018)
  • Author(s): Yuiki Kawada, Shunsuke Ohmura, Misaki Kobayashi, Wataru Nojo, Masaki Kondo, Yuka Matsuda, Junpei Matsuoka, Shinsuke Inuki, Shinya Oishi, Chao Wang, Tatsuo Saito, Masanobu Uchiyama, Takanori Suzuki, Hiroaki Ohno
  • Journal Title: Chem. Sci. Volume: 9 Issue: 44 Pages: 8416-8416
  • DOI: 10.1039/c8sc03525c
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ゴニオドミンAのDE環部の合成研究 (2019)
  • Author(s): 斉藤竜男
  • Organizer: 日本農芸化学会2019年度大会
• [Presentation] ゴニオドミンAのDE環部の合成研究 (2019)
  • Author(s): 斉藤竜男
  • Organizer: 第99回日本化学会春季年会
• [Presentation] 心筋細胞の増殖を活性化する新規化合物の合成研究 (2018)
  • Author(s): 近藤正樹，原弘典，武田憲文，斉藤竜男，畑裕，小室一成，内山真伸
  • Organizer: 第44回反応と合成の進歩シンポジウム
• [Presentation] 元素の特性を活かしたエーテル環合成反応の開発と海洋さんポリエーテル系天然物の合成研究 (2018)
  • Author(s): 斉藤竜男
  • Organizer: 有機合成化学協会関東支部若手研究者のためのセミナー
  • Invited