One-pot reactions for synthesis of non-standard peptides by controlling hydrogen-transfer fields

• Project Area: Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions
• Project/Area Number: 18H04247
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: Nagoya University
• Principal Investigator: 斎藤 進 名古屋大学, 物質科学国際研究センター, 教授 (90273268)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: アミノ酸 / アミド化 / 脱水縮合 / トリアザホスホリン / ペプチド / 精密水素移動触媒 / アミド / 脱水 / 有機分子触媒 / カルボン酸 / アミン / フォスファゼン / ジボロン / 精密水素移動場 / 非天然ペプチド / 分子触媒

Outline of Annual Research Achievements

アデノシントリリン酸（ATP）を模した触媒前駆体トリアザホスホリン(TAP)骨格をカテコールで修飾したリン化合物TAP(catec)3を触媒量用いた場合、芳香族カルボン酸とアミンとの縮合反応を効果的に促進し、アミド合成に有用なことを証明した。TAP(catec)3は化学量論量の反応剤として反応の初期段階では働くが、その結果分解を経て反応の後期で生成した環状カテコールホスファイトが触媒として機能するという「異なる活性種が段階的に働く反応促進作用」をNMRおよびESIMS
分析などを駆使して明確化した。現在本成果は論文として国際学術雑誌で印刷中である（Synthesis 2020）。
続いてTAP(catec)3を用いたアミド基構築反応は二種の異なるアミノ酸同士（N末端保護alpha-アミノ酸とC末端保護alpha-アミノ酸）の縮合によるペプチド鎖合成にも有用であることを証明した。実にアミノ酸側鎖が異なる38種類のalpha-アミノ酸へと応用することに成功し、ジペプチド、トリペプチド、テトラペプチドを合成することもできる。本成果は現在、学術論文を執筆中である。
TAP(catec)3はさらに多機能性である。例えばセリンやスレオニン残基をもつペプチドを用いた場合、分子内脱水縮合が進行し、効率的にオキサゾリン骨格が形成されることも見出した。触媒回転数は最高で１万回を優に超えている極めて活性の高い触媒系である。触媒作用機構についても一部明らかとなり、アミド基形成過程とは微妙に違う反応機構が提案された。本成果も現在、学術論文を執筆中である。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Iwa Womens University(韓国)
• [Int'l Joint Research] University of Cambridge(英国)
• [Journal Article] TAP(catecholate)3 as Promoter for Amide Bond Formation between Aromatic Acids and Amines (2020)
  • Author(s): Farzaneh Soleymani Movahed, Dinesh N. Sawant, Dattatraya B. Bagal, Susumu Saito*
  • Journal Title: Synthesis Volume: TBD
  • Peer Reviewed
• [Journal Article] Catalytic hydrogenation of N-protected alpha-amino acids using ruthenium complexes with monodentate phosphine ligands (2020)
  • Author(s): Akari Saito, Shota Yoshioka, Masayuki Naruto, Susumu Saito*
  • Journal Title: Adv. Synth. Catal. Volume: 362 Issue: 2 Pages: 424-429
  • DOI: 10.1002/adsc.201901298
  • Peer Reviewed
• [Journal Article] Photocatalytic CO2 reduction using a robust multifunctional iridium complex towards selective formation of formic acid (2020)
  • Author(s): Kenji Kamada, Jieun Jung* Taku Wakabayashi, Keita Sekizawa, Shunsuke Sato, Takeshi Morikawa, Shunichi Fukuzumi, Susumu Saito*
  • Journal Title: J. Am. Chem. Soc. Volume: 142 Issue: 23 Pages: 10261-10266
  • DOI: 10.1021/jacs.0c03097
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 高機能性金属錯体によるカルボン酸の水素化 (2020)
  • Author(s): 吉岡頌太，斎藤進
  • Journal Title: CSJ Current Review Volume: 37 Pages: 63-73
  • Peer Reviewed
• [Journal Article] Pd/TiO2-photocatalyzed self-condensation of primary amines to afford secondary amines at ambient temperature (2019)
  • Author(s): Lyu-Ming Wang, Mitushiro Arisawa, Susumu Saito*, Hiroshi Naka*
  • Journal Title: Org. Lett. Volume: 21 Issue: 2 Pages: 341-344
  • DOI: 10.1021/acs.orglett.8b03271
  • NAID: 120006623817
  • Peer Reviewed
• [Journal Article] Diboron-catalyzed dehydrative amidation of aromatic carboxylic acids with amines (2018)
  • Author(s): Dinesh N. Sawant, Dattatraya B. Bagal, Saeko Ogawa, Selvam Kaliyamoorthy, Susumu Saito
  • Journal Title: Organic Letters Volume: 20 Issue: 15 Pages: 4397-4400
  • DOI: 10.1021/acs.orglett.8b01480
  • NAID: 120006536931
  • Peer Reviewed
• [Journal Article] Photocatalytic hydrogenolysis of allylic alcohols for rapid access to platform chemicals and fine chemicals (2018)
  • Author(s): Takada Yuki、Caner Joaquim、Naka Hiroshi、Saito Susumu
  • Journal Title: Pure Appl. Chem. Volume: 90 Issue: 1 Pages: 167-174
  • DOI: 10.1515/pac-2017-0501
  • Peer Reviewed / Open Access
• [Journal Article] Catalytic hydrogenation of carboxylic acids using low-valent and high-valent metal complexes (2018)
  • Author(s): Shota Yoshioka, Susumu Saito
  • Journal Title: Chemical Communications Volume: 54 Issue: 95 Pages: 13319-13330
  • DOI: 10.1039/c8cc06543h
  • NAID: 120006534459
  • Peer Reviewed
• [Journal Article] Photocatalytic N-Methylation of Amines over Pd/TiO2 for the Functionalization of Heterocycles and Pharmaceutical Intermediates (2018)
  • Author(s): Lyu-Ming Wang, Kellie Jenkinson, Andrew E. H. Wheatley, Keiko Kuwata, Susumu Saito, Hiroshi Naka
  • Journal Title: ACS Sustainble Chemical Engineering Volume: 6 Issue: 11 Pages: 15419-15424
  • DOI: 10.1021/acssuschemeng.8b03855
  • NAID: 120006577073
  • Peer Reviewed
• [Journal Article] N-Alkylation of functionalized amines with alcohols using a copper?gold mixed photocatalytic system (2018)
  • Author(s): Wang Lyu-Ming、Morioka Yuna、Jenkinson Kellie、Wheatley Andrew E. H.、Saito Susumu、Naka Hiroshi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 6931-6931
  • DOI: 10.1038/s41598-018-25293-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] カルボン酸水素化触媒の高機能化と光学活性化合物合成への展開 (2019)
  • Author(s): 斎藤進
  • Organizer: 長瀬科学技術振興財団 平成30年度成果発表会
  • Invited
• [Presentation] Semiconductor Photocatalysis of Renewable Alcohol and Amine Feedstock: Hydrogen Management for Fine Chemical Synthesis (2019)
  • Author(s): Susumu Saito
  • Organizer: International Conference on Photocatalysis and Photoenergy 2019 (ICOPP2019)
  • Int'l Joint Research / Invited
• [Presentation] 精密錯体触媒を用いる安定カルボン酸誘導体の水素化法の開拓と応用 (2019)
  • Author(s): 斎藤進
  • Organizer: 第115回有機合成シンポジウム企業冠賞受賞講演
  • Invited
• [Presentation] Looking for the bridge between photo-organic synthesis and surface catalysis science (2019)
  • Author(s): Susumu Saito
  • Organizer: The 1st Workshop of Reaction Infography (R-ing) Unit of WPI-next, Nagoya University
  • Int'l Joint Research / Invited
• [Presentation] Catalytic Hydrogen Management for Sustainable Future (2019)
  • Author(s): Susumu Saito
  • Organizer: NU-UoE JD and JSPS CtC Joint Workshop “New Horizons in Chemistry and Materials Science
  • Int'l Joint Research / Invited
• [Presentation] 再生可能資源とCO2からのモノづくり (2019)
  • Author(s): 斎藤進
  • Organizer: 夢ナビTalk 2019
  • Invited
• [Presentation] 水素と光を操り有機物質生産を変える (2019)
  • Author(s): 斎藤進
  • Organizer: 夢ナビ講義ライブ 2019
  • Invited
• [Presentation] Catalytic hydrogen management: Dehydrogenative photocatalysis follows hydrogenation of carboxylic acid derivatives (2019)
  • Author(s): Susumu Saito
  • Organizer: School of Chemical Engineering, Nanjing University of Science and Technology (NJUST) Chemical Enginnering Visiting Professor Seminar
  • Int'l Joint Research / Invited
• [Presentation] Hydrogenation catalysis followed by semiconductor photocatalysis for fine chemicals synthesis (2019)
  • Author(s): Susumu Saito
  • Organizer: Zhejiang University Pharmaceutical Seminar
  • Int'l Joint Research / Invited
• [Presentation] Catalytic hydrogen management: Dehydrogenative photocatalysis follows hydrogenation of carboxylic acid derivatives (2019)
  • Author(s): Susumu Saito
  • Organizer: School of Chemical Engineering, Soochow University, SU Materials Chemistry Seminar
  • Int'l Joint Research / Invited
• [Presentation] Catalytic hydrogen management: Dehydrogenative photocatalysis follows hydrogenation of carboxylic acid derivatives (2019)
  • Author(s): Susumu Saito
  • Organizer: School of Chemical Engineering, Nanjing Tech University, NJTech Chemistry Seminar
  • Int'l Joint Research / Invited
• [Presentation] TiO2-based photocatalysis for selective organic synthesis and fine chemicals (2019)
  • Author(s): Susumu Saito
  • Organizer: 3rd International Solar Fuels Conference/International Conference on Artificial Photosynthesis-2019
  • Int'l Joint Research / Invited
• [Presentation] Catalytic hydrogen management for sustainable resources：hydrogenation under dark and dehydrogenation under light (2019)
  • Author(s): Susumu Saito
  • Organizer: Kolloquium fur Chemie und Chemische Biologie, Fachbereich Chemie, Phillipps-Universitat Marburg (University of Marburg)
  • Int'l Joint Research / Invited
• [Presentation] Catalytic hydrogen management for sustainable resources：hydrogenation under dark and dehydrogenation under light (2019)
  • Author(s): Susumu Saito
  • Organizer: OC Colloquium, Justus-Liebig-Universitat-Giessen (University of Giessen)
  • Int'l Joint Research / Invited
• [Presentation] Catalytic hydrogen management for sustainable resources：hydrogenation under dark and dehydrogenation under light (2019)
  • Author(s): Susumu Saito
  • Organizer: Institute of Technical and Macromolecular Chemistry Seminar, RWTH Aahen University
  • Int'l Joint Research / Invited
• [Presentation] Catalytic hydrogen management for sustainable resources：hydrogenation under dark and dehydrogenation under light (2019)
  • Author(s): Susumu Saito
  • Organizer: WWU Chemistry Seminar, University of Muenster, Muenster
  • Int'l Joint Research / Invited
• [Presentation] 有機合成・物質生産を変えるか：触媒的水素マネージメント (2019)
  • Author(s): 斎藤進
  • Organizer: 第2回名古屋大学理学部化学教室IDAB委員会，名古屋大学
  • Invited
• [Presentation] Catalytic hydrogen management for renewable feedstock：hydrogenation under dark and dehydrogenation under light (2018)
  • Author(s): Susumu Saito
  • Organizer: International Conference on Advanced and Applied Petroleum, Petrochemicals, and Polymers in 2018 (ICAPPP 2018)
  • Int'l Joint Research / Invited
• [Remarks] 水素が与えてくれる、持続可能な社会への夢
  • URL: https://yumenavi.info/lecture_sp.aspx?GNKCD=g009882&OraSeq=56&ProId=WNA002_Sp&SerKbn=Z&SearchMod=6&Page=1&KeyWord=
• [Remarks] 再生可能資源やCO2からのモノづくり
  • URL: https://talk.yumenavi.info/archives/2534?site=p&close=true