Development of chiral organocatalyst utilizing "distal group participation"

• Project/Area Number: 15K05495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: KUDO Kazuaki 東京大学, 生産技術研究所, 教授 (80251669)
• Research Collaborator: AKAGAWA Kengo ; SATOU Junichi ; HIGUCHI Junichi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 有機分子触媒 / 不斉触媒 / ペプチド / ヒスチジン / プロリン / 加水分解 / ライブラリスクリーニング / Baylis-Hillman反応 / 触媒 / 協同効果 / ライブラリ / 多点活性化

Outline of Final Research Achievements

Before starting this project, we had found that a certain peptide behaves as a catalyst for a specific addition reaction with high activity and high enantioselectivity. We had uncovered that such a catalytic performance of peptide came from cooperative action of proline and histidine in the peptide chain. We tentatively named this phenomenon as "distal group participation".
This time we tried to clarify how general this "distal group participation" concept is. We tried several reactions with several peptides, and found that this concept could also be applicable toward hydrolysis reaction. In addition, we could find completely new peptide catalyst having proline and histidine. These findings show that there remains further extendability with the "distal group participation".

Research Products

• [Journal Article] Biomimetic iterative method for polyketide synthesis (2017)
  • Author(s): Kengo Akagawa, Kazuaki Kudo
  • Journal Title: Chemical Communications Volume: 53 Issue: 62 Pages: 8645-8648
  • DOI: 10.1039/c7cc04033d
  • Peer Reviewed
• [Journal Article] Development of Selective Peptide Catalysts with Secondary Structural Frameworks (2017)
  • Author(s): Kengo Akagawa, Kazuaki Kudo
  • Journal Title: Accounts of Chemical Research Volume: 50 Issue: 10 Pages: 2429-2439
  • DOI: 10.1021/acs.accounts.7b00211
  • Peer Reviewed
• [Journal Article] Helical-Peptide-Catalyzed Enantioselective Michael Addition Reaction and Their Mechanistic Insights (2016)
  • Author(s): Atsushi Ueda, Tomohiro Umeno, Mitsunobu Doi, Kengo Akagawa, Kazuaki Kudo, Masakazu Tanaka
  • Journal Title: The Journal of Organic Chemistry Volume: 81 Issue: 15 Pages: 6343-6356
  • DOI: 10.1021/acs.joc.6b00982
  • Peer Reviewed
• [Journal Article] Library Screening in Aqueous Media To Develop a Highly Active Peptide Catalyst for Enantioselective Michael Addition of a Malonate (2016)
  • Author(s): Kengo Akagawa, Yumika Iwasaki, Kazuaki Kudo
  • Journal Title: European Journal of Organic Chemistry Volume: - Issue: 26 Pages: 4460-4464
  • DOI: 10.1002/ejoc.201600828
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Exploration of Structural Frameworks for Reactive and Enantioselective Peptide Catalysts by Library Screenings (2016)
  • Author(s): Kengo Akagawa, Junichi Satou, Kazuaki Kudo
  • Journal Title: The Journal of Organic Chemistry Volume: 81 Issue: 19 Pages: 9396-9401
  • DOI: 10.1021/acs.joc.6b01591
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Determination of the Absolute Configuration of Side Chains of Basic Amino Acid Residues Using the Water-Soluble Porphyrin-Based Exciton Chirality Method (2016)
  • Author(s): S. Hattori, K. Akagawa, K. Kudo, *K. Ishii
  • Journal Title: J. Phys. Chem. B Volume: 120 Issue: 39 Pages: 10280-10287
  • DOI: 10.1021/acs.jpcb.6b07925
  • Peer Reviewed
• [Journal Article] Solvolysis of Formylphenyl Esters by a Bifunctional Peptide Catalyst (2016)
  • Author(s): K. Akagawa, K. Kudo
  • Journal Title: Chemistry Letters Volume: 45 Issue: 3 Pages: 300-302
  • DOI: 10.1246/cl.151154
  • NAID: 130005132168
  • ISSN: 0366-7022, 1348-0715
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Asymmetric Epoxidation of Enones by Peptide-Based Catalyst: A Strategy Inverting Juliá–Colonna Stereoselectivity (2016)
  • Author(s): K. Akagawa,T. Hirata, K. Kudo
  • Journal Title: Synlett Volume: 27 Issue: 08 Pages: 1217-1222
  • DOI: 10.1055/s-0035-1560597
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Kinetic Resolution of a Planar-Chiral [2.2]Paracyclophane Derivative by Helical-Peptide-Catalyzed Michael Addition of Nitromethane (2015)
  • Author(s): K. Akagawa, N. Nishi, I. Yoshikawa, K. Kudo
  • Journal Title: Eur. J. Org. Chem. Volume: 2015 Issue: 23 Pages: 5055-5059
  • DOI: 10.1002/ejoc.201500594
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Peptide-Catalyzed Desymmetrization of an Achiral Ferrocenyl Compound To Induce Planar Chirality (2015)
  • Author(s): K. Akagawa, M. Akiyama, K. Kudo
  • Journal Title: Eur. J. Org. Chem. Volume: 2015 Issue: 18 Pages: 3894-3898
  • DOI: 10.1002/ejoc.201500428
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 固相担持ペプチド触媒を用いた面不斉[n]パラシクロファンの速度論的光学分割 (2018)
  • Author(s): 樋口淳一,赤川賢吾,工藤一秋
  • Organizer: 日本化学会第98春季年会
• [Presentation] Development of Tandem Enantioselective Intramolecular Rauhut Currier Reaction and Aldol Condensation Promoted by Peptide Catalyst (2018)
  • Author(s): Y.Tian,Z.Du,K.Akagawa,K.Kudo
  • Organizer: 日本化学会第98春季年会
• [Presentation] 生合成機構を模倣したポリケチドの固相合成法の開発 (2018)
  • Author(s): 竹内優太,赤川賢吾,工藤一秋
  • Organizer: 日本化学会第98春季年会
• [Presentation] Development of Peptide Catalysts for Activating Substrates via Michael-Type Addition (2016)
  • Author(s): 杜肇南, 赤川賢吾, 工藤一秋
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都）
  • Year and Date: 2016-03-24
• [Presentation] 大規模ライブラリを用いた骨格探索とファインチューニングによるペプチド触媒の開発 (2016)
  • Author(s): 佐藤潤一, 赤川賢吾, 工藤一秋
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都）
  • Year and Date: 2016-03-24
• [Presentation] ライブラリ法による新規ペプチド触媒の探索 (2016)
  • Author(s): 工藤一秋
  • Organizer: 第65回高分子討論会
  • Place of Presentation: 神奈川大学
  • Invited
• [Presentation] Development of selective peptide catalysts having secondary structures (2015)
  • Author(s): K. Kudo, K. Akagawa
  • Organizer: International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Honolulu（USA)
  • Year and Date: 2015-12-17
  • Int'l Joint Research
• [Presentation] Screening of peptide libraries for discovering efficient aminocatalysts (2015)
  • Author(s): K. Akagawa, J. Satou, K. Kudo
  • Organizer: International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Honolulu(USA)
  • Year and Date: 2015-12-16
  • Int'l Joint Research
• [Presentation] 大規模ライブラリスクリーニングによる新規ペプチド触媒の開発 (2015)
  • Author(s): 佐藤潤一, 赤川賢吾, 工藤一秋
  • Organizer: 第5回CSJ化学フェスタ
  • Place of Presentation: 船堀タワーホール（東京都）
  • Year and Date: 2015-10-13
• [Presentation] Asymmetric Intramolecular Morita-Baylis-Hillman Reaction Promoted by Peptide Catalysts with Multiple Functional Groups (2015)
  • Author(s): 杜肇南, 赤川賢吾, 工藤一秋
  • Organizer: 第5回CSJ化学フェスタ
  • Place of Presentation: 船堀タワーホール（東京都）
  • Year and Date: 2015-10-13
• [Presentation] 第一級アミン型ペプチド不斉触媒の開発 (2015)
  • Author(s): 工藤一秋
  • Organizer: 第64回高分子討論会
  • Place of Presentation: 東北大学（仙台）
  • Year and Date: 2015-09-15
• [Book] 有機化学 (2015)
  • Author(s): 工藤一秋，渡辺正
  • Total Pages: 204
  • Publisher: 化学同人
• [Remarks] 発表論文
  • URL: http://www.iis.u-tokyo.ac.jp/~kkudo/publication.html
• [Remarks] 総説・解説
  • URL: http://www.iis.u-tokyo.ac.jp/~kkudo/review.html