Development of regioselective sp3 C-H functionalization catalyst with substrate recognition site
| Project/Area Number |
18K06545
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Oisaki Kounosuke 東京大学, 大学院薬学系研究科(薬学部), 講師 (00583999)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | C-H活性化 / 有機ラジカル / フォトレドックス触媒 / 水素原子移動触媒 / 結合弱化触媒 / 有機合成化学 / 化学選択性 / 均一系触媒 |
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| Outline of Final Research Achievements |
We have been working on the development of catalysts that enable catalytic control of site-selectivity, which is an unsolved problem in catalytic C(sp3)-H transformation.
(1) By designing HAT catalysts with alcohol recognition moiety, we attempted to achieve site-selective C(sp3)-H transformations through a pseudo-intramolecular transition state. However, this approach was abandoned in the face of various problems.
(2) We conducted DFT-guided screening of bond-weakening catalysts that could lower the bond dissociation energy (BDE) by recognizing alcohol moiety, and found silicate or borate species to be candidates. Based on this finding, we developed a cooperative catalytic system promoting alcohol alpha-C-H alkylations using Martin spirosilane and electron-deficient boric acid as the embodiment of bond-weakening catalyst.
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| Academic Significance and Societal Importance of the Research Achievements |
最終生成物に頻度高く含まれる官能基（ヒドロキシル基やカルボニル基など）を足がかりとし、各々のC-H結合を区別したうえで位置選択的な変換可能な触媒を開発できれば、物質機能を担保したうえでの構造展開を可能とするLate-Stage誘導体化法の拡充や、複雑化合物の合成短工程化にも寄与し、機能性物質創製プロセスを加速させるような方法論となることが期待される。本研究にて開発に成功した結合弱化触媒系は、現在世界中の研究者が取り組んでいるC(sp3)-H変換触媒開発とその位置選択性制御という重要課題に対し、解決をもたらしうる全く新たな角度からの触媒設計指針を提供する。
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Report
(4 results)
Research Products
(65 results)
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[Presentation] Tryptophan-Targeted Homogeneous Antibody-Drug Conjugates2019
Author(s)
Katsuya Maruyama, Takashi Ishiyama, Atsushi Kawamura, Kuniko Saiki, Yuki Kobayashi, Yohei Seki, Keita Iguchi, Masaru Mitsuda, Kounosuke Oisaki, Motomu Kanai
Organizer
The 1st International Symposium on Hybrid Catalysis for Enabling Molecular Synthesis on Demand
Related Report
Int'l Joint Research
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[Presentation] MSn Analyses for Tryptophan-Conjugated ADC Mimic by Miniature MALDI Digital Ion Trap Mass Spectrometer (MALDI-DIT-MS)2019
Author(s)
Hideharu Shichi, Shuichi Nakaya, Katsuya Maruyama, Kosuke Hosoi, Takashi Nishikaze, Koichi Kojima, Kei Kodera, Sadanori Sekiya, Shinichi Iwamoto, Kounosuke Oisaki, Motomu Kanai, Koichi Tanaka
Organizer
The 67th ASMS Conference on Mass Spectrometry and Allied Topics
Related Report
Int'l Joint Research
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[Presentation] Electrochemical Tryptophan-Selective Bioconjugation2019
Author(s)
Kounosuke Oisaki, Eisho Toyama, Katsuya Maruyama, Tomoya Sugai, Mio Kondo, Shigeyuki Masaoka, Tsuyoshi Saitoh, Motomu Kanai
Organizer
European Federation for Medicinal Chemistry International Symposium on Advances in Synthetic and Medicinal Chemistry (EFMC-ASMC’19)
Related Report
Int'l Joint Research
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