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Strategic Molecular Design Aiming at Streamlined Chemical Transformations

Research Project

Project/Area Number 20H02746
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 33020:Synthetic organic chemistry-related
Research InstitutionKeio University

Principal Investigator

Kumagai Naoya  慶應義塾大学, 薬学部(芝共立), 教授 (40431887)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsヘテロ環 / アミド化 / ホウ素 / キノリン / マクロサイクル / 触媒 / グリーンケミストリー / 金属クラスター / 超分子 / アミド / 非平面芳香族 / ホスト分子 / 超分子錯体 / 非共有結合性相互作用
Outline of Research at the Start

新奇分子の探求は化学を最も化学たらしめる基礎研究の一源流であり,化学者自身が創造者となりオリジナルの物性・機能探索を縦横に展開するための源泉となる。本研究では,独自の新奇分子デザインおよびその戦略的構築を基盤とし,効率的な触媒的分子変換反応を開拓することを主眼とする。分子変換にはサステイナビリティが無視できない時代に突入しており,既存技術の延長線上での解決法の策定は困難と言わざるを得ない。本研究では,従来型の触媒設計から脱却し,抜本的な新奇構造デザインが具現する新奇機能創発アプローチをとることで,反応の超高率化を実現し各種分子変換に最高解を提供することを目指す。

Outline of Final Research Achievements

A new improved synthetic route for DATB derivatives has been identified. This chromatography free method allows us to access wide variety of derivatives in a highly reliable and efficient way, leading to further exploration in practical direct admiration catalysis and integrated one-pot transformations. As for the development of non-flat quinoline oligomers, we have developed the synthetic protocol for TEtraQuinoline and oxo-TriQuinoline. They can serve as a tetra dentate and tridentate nitrogen-based macrocyclic ligands, exhibiting attractive physicochemical properties and catalytic competency.

Academic Significance and Societal Importance of the Research Achievements

DATBはアミド結合形成における強力な触媒として作用することから,試薬援用型の工業的なアミド合成をサステイナブルなクリーンプロセスに刷新する可能性を秘めており,今回見出した新規DATB合成法により社会実装に向けた展開が可能になる。新たな立体型キノリンオリゴマーは予想以上の物性,触媒性能を示すことが明らかとなり,資源に乏しい我が国においても,軽元素を巧みに配列させることで機能性分子の新規開発が十分に可能である事を示した。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (53 results)

All 2023 2022 2021 2020 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 3 results) Presentation (36 results) (of which Int'l Joint Research: 3 results,  Invited: 13 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] TEtraQuinolines: A Missing Link in the Family of Porphyrinoid Macrocycles2023

    • Author(s)
      Xu Wei、Nagata Yuuya、Kumagai Naoya
    • Journal Title

      Journal of the American Chemical Society

      Volume: 145 Issue: 4 Pages: 2609-2618

    • DOI

      10.1021/jacs.2c12582

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Azo-tagged C4N4 fluorophores: unusual overcrowded structures and their application to fluorescent imaging2023

    • Author(s)
      Kohei Miki、Takizawa Naoki、Tsutsumi Ryosuke、Xu Wei、Kumagai Naoya
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 21 Issue: 14 Pages: 2889-2893

    • DOI

      10.1039/d3ob00049d

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Less Is More: N(BOH)2 Configuration Exhibits Higher Reactivity than the B3NO2 Heterocycle in Catalytic Dehydrative Amide Formation2023

    • Author(s)
      Opie Christopher R.、Noda Hidetoshi、Shibasaki Masakatsu、Kumagai Naoya
    • Journal Title

      Organic Letters

      Volume: 25 Issue: 4 Pages: 694-697

    • DOI

      10.1021/acs.orglett.2c04382

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxygen-Fueled Iterative Hydride Transfer Driven by a Rigid Planar Architecture2022

    • Author(s)
      Karimata Taiga、Adachi Shinya、Shibasaki Masakatsu、Kumagai Naoya
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 70 Issue: 9 Pages: 595-598

    • DOI

      10.1248/cpb.c22-00215

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2022-09-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Strategic Synthesis of Asymmetrically Substituted C4N4 Fluorophores2021

    • Author(s)
      Wei Xu, Miki Kohei, Masakatsu Shibasaki, Naoya Kumagai
    • Journal Title

      Synthesis

      Volume: 53 Issue: 18 Pages: 3355-3360

    • DOI

      10.1055/a-1516-9399

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Catalytic Asymmetric Addition of Alkylnitriles to Aldehydes with Designed Nickel-Carbene Complexes2021

    • Author(s)
      Akira Saito, Shinya Adachi, Naoya Kumagai, Masakatsu Shibasaki
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 60 Issue: 16 Pages: 8739-8743

    • DOI

      10.1002/anie.202016690

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly Enantio- and Diastereoselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes from α,β-Unsaturated Amides and Stabilized Sulfur Ylides Catalyzed by a Chiral Copper(I) Complex2021

    • Author(s)
      Santosh K. Pagire, Naoya Kumagai, and Masakatsu Shibasaki
    • Journal Title

      ACS Catalysis

      Volume: 11 Issue: 18 Pages: 11597-11606

    • DOI

      10.1021/acscatal.1c02723

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytic Asymmetric 1,3-Dipolar Cycloaddition of α,β-Unsaturated Amide and Azomethine Imine2020

    • Author(s)
      Zhao Li, Naoya Kumagai, and Masakatsu Shibasaki
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 68 Issue: 6 Pages: 552-554

    • DOI

      10.1248/cpb.c20-00130

    • NAID

      130007850053

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2020-06-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Catalytic Asymmetric Addition of α‐Fluoronitriles to Aldehydes2020

    • Author(s)
      Pandur Venkatesan Balaji, Zhao Li, Akira Saito, Naoya Kumagai, Masakatsu Shibasaki
    • Journal Title

      Chem. Eur. J.

      Volume: 26 Issue: 67 Pages: 15524-15527

    • DOI

      10.1002/chem.202004743

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, Synthesis, and Application of Multiboron Heterocycle to Direct Amidation Catalyst2020

    • Author(s)
      Noda Hidetoshi、Shibasaki Masakatsu、Kumagai Naoya
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 78 Issue: 10 Pages: 971-978

    • DOI

      10.5059/yukigoseikyokaishi.78.971

    • NAID

      130007923156

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Different Faces of [Ru(bpy)3Cl2] and fac[Ir(ppy)3] Photocatalysts: Redox Potential Controlled Synthesis of Sulfonylated Fluorenes and Pyrroloindoles from Unactivated Olefins and Sulfonyl Chlorides2020

    • Author(s)
      Santosh Kisan Pagire , Naoya Kumagai, Masakatsu Shibasaki
    • Journal Title

      Org. Lett.

      Volume: 22 Issue: 20 Pages: 7853-7858

    • DOI

      10.1021/acs.orglett.0c02760

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct catalytic asymmetric and anti-selective vinylogous addition of butenolides to chromones2020

    • Author(s)
      Cui Jin、Kumagai Naoya、Watanabe Takumi、Shibasaki Masakatsu
    • Journal Title

      Chemical Science

      Volume: 11 Issue: 27 Pages: 7170-7176

    • DOI

      10.1039/d0sc01914c

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Introduction of a 7-aza-6-MeO-indoline auxiliary in Lewis-acid/photoredox cooperative catalysis: highly enantioselective aminomethylation of α,β-unsaturated amides2020

    • Author(s)
      Santosh K. Pagire, Naoya Kumagai* and Masakatsu Shibasaki*
    • Journal Title

      Chem. Sci.

      Volume: 2020 Issue: 20 Pages: 5168-5174

    • DOI

      10.1039/d0sc01890b

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] (2R,3S)‐3,4,4,4‐Tetrafluorovaline: A Fluorinated Bioisostere of Isoleucine2020

    • Author(s)
      Lennart Brewitz, Hidetoshi Noda, Naoya Kumagai*, Masakatsu Shibasaki*
    • Journal Title

      Eur. J. Org. Chem.

      Volume: 2020 Issue: 11 Pages: 1745-1752

    • DOI

      10.1002/ejoc.202000109

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Z-Enolate Geometry in the Thioamide Aldol Reaction Illuminated by the 7-Azaindoline Auxiliary2020

    • Author(s)
      Roman Pluta, Zhao Li, Naoya Kumagai*, and Masakatsu Shibasaki*
    • Journal Title

      Org. Lett.

      Volume: 22 Issue: 3 Pages: 791-794

    • DOI

      10.1021/acs.orglett.9b04120

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 特殊ヘテロ環の化学2023

    • Author(s)
      熊谷直哉
    • Organizer
      京都大学大学院工学研究科 講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Palladium応答性新規C4N4蛍光プローブの創製2023

    • Author(s)
      公平実希、新村万緒、Wei Xu、熊谷直哉
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 光応答性自己集合3量体分子[HyAl-Py]3の機能開発2023

    • Author(s)
      鶴岡航太朗、野崎雅人、熊谷直哉
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] キノリン/インドール環状4量体(Q2In2)のデザイン・合成および物性評価2023

    • Author(s)
      木原和輝、木村美玲、Wei Xu、熊谷直哉
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] キノリン及びナフタレンを構成単位とする環状4量体の合成と物性2023

    • Author(s)
      野仲はる、Wei Xu、熊谷直哉
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 酸素原子架橋型TEtraQuinoline(o-TEQ)の合成とその物理化学的特性2023

    • Author(s)
      小林透威、熊谷直哉
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TEtraQuinoline (TEQ) and Other Cyclic Quinoline Oligomers, a New Family of Macrocycles2023

    • Author(s)
      Wei Xu, Haru Nonaka, Ryota Yagami, Mizuki Nishiwaki, Ayami Takeda, Naoya Kumagai
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 酸素原子架橋による立体型TriQuinolineの合成とその物理化学的特性2023

    • Author(s)
      小林透威、根本春美、熊谷直哉
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 一原子欠損π平面環状分子トリキノリン誘導体DQMQzの新規合成法とその機能展開2023

    • Author(s)
      狩俣太雅、Wei Xu、山崎洋子、熊谷直哉
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ジアミノピリミジン型アゾ化合物:ねじれ型構造特性と蛍光バイオイメージングへの応用2023

    • Author(s)
      公平実希、滝沢直己、堤亮祐、Wei Xu、熊谷直哉
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 特殊ヘテロ環の化学2022

    • Author(s)
      熊谷直哉
    • Organizer
      大阪大学産業技術研究所 講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 特殊ヘテロ環の化学2022

    • Author(s)
      熊谷直哉
    • Organizer
      有機合成化学協会関東支部ミニシンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 特殊ヘテロ環の化学2022

    • Author(s)
      熊谷直哉
    • Organizer
      京都工芸繊維大学 講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 特殊ヘテロ環の化学2022

    • Author(s)
      熊谷直哉
    • Organizer
      第45回フッ素化学討論会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Chemistry Driven by Quinoline Oligomers2022

    • Author(s)
      Naoya Kumagai
    • Organizer
      SICC-11
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Design, Synthesis, Properties of TEtraQuinoline (TEQ) and Its Application as Zinc Cation Fluorescent Probe2022

    • Author(s)
      Wei Xu, Naoya Kumagai,
    • Organizer
      25th IUPAC International Conference on Physical Organic Chemistry (ICPOC 25)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Design, Synthesis, and Physicochemical Properties of Oxygen-Embedded TriQuinoline2022

    • Author(s)
      Toi Kobayashi, Naoya Kumagai
    • Organizer
      25th IUPAC International Conference on Physical Organic Chemistry (ICPOC 25)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規ピアノスツール型三座配位子; oxa-TriQuinoline (o-TQ)2022

    • Author(s)
      小林透威、熊谷直哉
    • Organizer
      第32回基礎有機化学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 立体障害性オルトテトラアリールアゾ化合物の合成とその低酸素バイオイメージングへの応用2022

    • Author(s)
      公平実希、堤亮祐、熊谷直哉
    • Organizer
      第32回基礎有機化学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 特殊ヘテロ6員環化合物DATBの改良合成法の開発2022

    • Author(s)
      堤亮祐、柏木伸章、熊谷直哉
    • Organizer
      日本化学会 第103春季年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Design and Synthesis of Oxygen Embedded TriQuinoline and Its Strategic Applications2022

    • Author(s)
      Toi Kobayashi, Naoya Kumagai
    • Organizer
      日本化学会第102春期年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Design, Synthesis, Properties of TEtraQuinoline (TEQ) and Its Application as Zinc(II) Ion Fluorescence Sensor2022

    • Author(s)
      Wei Xu, Naoya Kumagai
    • Organizer
      日本化学会第102春期年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] π平面型大環状イミニウム塩の酸化触媒機能2022

    • Author(s)
      狩俣太雅, 熊谷直哉
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 立体障害性オルトテトラアリールアゾ化合物の合成とその応用2022

    • Author(s)
      公平実希, 堤亮祐, 熊谷直哉
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] アルキルニトリルを基質に用いた触媒的不斉付加反応の開発2022

    • Author(s)
      齊藤誠, 足立慎弥, 熊谷直哉, 柴崎正勝
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒト肝細胞を用いたトラッピング試験系の確立とその評価2022

    • Author(s)
      柴崎智香子, 増野匡彦, 熊谷直哉, 大江知之
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マロン酸型フラーレン誘導体はSARS-CoV-2メインプロテアーゼを強く阻害する2022

    • Author(s)
      片岸大紀, 岩﨑彩希子, 安田大輔, 高橋恭子, 中村成夫, 増野匡彦, 熊谷直哉, 大江知之
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 胆道がん治療薬を目指したフェンチコナゾール誘導体の合成と評価2022

    • Author(s)
      木原和輝, 柏木伸章, 村松俊英, 高橋恭子, 中村成夫, 熊谷直哉, 増野匡彦, 齋藤義正, 大江知之
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] パーキンソン病治療薬を目指したオキシカムアナログIY104のADME評価および類縁体合成2022

    • Author(s)
      鶴岡航太朗, 高橋恭子, 中村成夫, 熊谷直哉, 増野匡彦, 大久保知子, 眞鍋貴行, 田﨑嘉一, 大江知之
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 特殊ヘテロ環の化学2021

    • Author(s)
      熊谷直哉
    • Organizer
      白鷺セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 特殊ヘテロ環の化学2021

    • Author(s)
      熊谷直哉
    • Organizer
      京都大学薬学部講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 特殊へテロ環の化学2020

    • Author(s)
      熊谷直哉
    • Organizer
      有機合成化学講習会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 特殊へテロ環の化学2020

    • Author(s)
      熊谷直哉
    • Organizer
      九州大学講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ラクしてスライド用3D動画をつくる2020

    • Author(s)
      熊谷直哉
    • Organizer
      第10回化学フェスタ
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 特殊へテロ環の化学2020

    • Author(s)
      熊谷直哉
    • Organizer
      長崎大学講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 特殊へテロ環の化学2020

    • Author(s)
      熊谷直哉
    • Organizer
      高砂香料工業講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 平べったくない「ポルフィリン2.0」の創製-平面化合物では到達不可能な超機能性分子への展開に期待-

    • URL

      https://www.keio.ac.jp/ja/press-releases/2023/2/2/28-135221/

    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物、及びその製造方法2021

    • Inventor(s)
      熊谷直哉、Wei Xu
    • Industrial Property Rights Holder
      熊谷直哉、Wei Xu
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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