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異種アジド基の選択的な利用を鍵とする機能性中分子の迅速合成法の開発

Publicly Offered Research

Project AreaMiddle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis.
Project/Area Number 18H04386
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Research InstitutionTokyo Medical and Dental University

Principal Investigator

細谷 孝充  東京医科歯科大学, 生体材料工学研究所, 教授 (60273124)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords有機化学 / ケミカルバイオロジー / 分子プローブ / アジド / 中分子 / アルキン / クリック反応 / ホスフィン / 複素環
Outline of Annual Research Achievements

中分子化合物は、生物活性など、その魅力的な性質にもかかわらず、これらを用いる生命有機化学は小分子を扱う研究と同じアプローチで行われてきたため、所望の中分子を供給するためには多大な労力・時間を要する。これに対して本研究では、アジド化学に基づく分子連結を基盤として、複雑な構造の中分子を用いる生命有機化学研究を大きく加速させる手法の創出を目指している。特に、区別して利用できる連結部位を組み込んだプラットフォーム分子の開発と、これを用いた逐次分子連結反応の開発に取り組み、多成分を集積した中分子化合物群の簡便合成法を開発してきた。
平成31/令和元年度は、主に、以下の2つのテーマに取り組んだ。まず、(1)前年度までに開発に成功した、アジド化合物にAmphosを作用させることで安定なホスファジドを形成し、クリック反応から保護する手法の高度化に取り組んだ。その結果、本手法により様々なアジド化合物を保護できることを明らかにするとともに、アジド基を損なうことなく、エステルの還元など、共存する他の官能基を変換できることを明らかにした。また、(2)異なる環境のアジド基が示す、特異な反応性を利用したマルチアジド型プラットフォーム分子を用いる機能性分子の集積法の開発に関して、以前開発した芳香族アジドと脂肪族アジドを有するジアジドビルディングブロックを用いた、遷移金属触媒による炭素-ヘテロ原子結合反応を検討した。とくに、ジアジド型のヨウ化アリールのアミノ化反応について精査したところ、パラジウム触媒を用いるカップリング反応がアジドを損なうことなく、効率的に進行する条件を見出した。さらに、本反応条件で医薬品化合物のような多彩な官能基を有するアミン類とのカップリングにも成功した。

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。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (32 results)

All 2020 2019 2018

All Journal Article (21 results) (of which Peer Reviewed: 21 results,  Open Access: 11 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Consecutive Aryne Generation Strategy for the Synthesis of 1,3-Diarylpyrazoles2020

    • Author(s)
      Kobayashi Tsuneyuki、Hosoya Takamitsu、Yoshida Suguru
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 85 Issue: 6 Pages: 4448-4462

    • DOI

      10.1021/acs.joc.0c00172

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Phenoxathiins and Phenothiazines by Aryne Reactions with Thiosulfonates2020

    • Author(s)
      Kanemoto Kazuya、Sakata Yuki、Hosoya Takamitsu、Yoshida Suguru
    • Journal Title

      Chemistry Letters

      Volume: 49 Issue: 5 Pages: 593-596

    • DOI

      10.1246/cl.200132

    • NAID

      130007840185

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functionalization of a Single C?F Bond of Trifluoromethylarenes Assisted by an ortho ‐Silyl Group Using a Trityl‐Based All‐in‐One Reagent with Ytterbium Triflate Catalyst2020

    • Author(s)
      Kim Youngchan、Kanemoto Kazuya、Shimomori Ken、Hosoya Takamitsu、Yoshida Suguru
    • Journal Title

      Chemistry ? A European Journal

      Volume: 26 Issue: 28 Pages: 6136-6140

    • DOI

      10.1002/chem.202001315

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facile assembly of three cycloalkyne-modules onto a platform compound bearing thiophene S,S-dioxide moiety and two azido groups2020

    • Author(s)
      Meguro Tomohiro、Sakata Yuki、Morita Takamoto、Hosoya Takamitsu、Yoshida Suguru
    • Journal Title

      Chemical Communications

      Volume: 56 Issue: 34 Pages: 4720-4723

    • DOI

      10.1039/d0cc01810d

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modular Synthesis of Unsymmetrical Doubly-ring-fused Benzene Derivatives Based on a Sequential Ring Construction Strategy Using Oxadiazinones as a Platform Molecule2019

    • Author(s)
      Meguro Tomohiro、Chen Shengnan、Kanemoto Kazuya、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Chemistry Letters

      Volume: 印刷中 Issue: 6 Pages: 582-585

    • DOI

      10.1246/cl.190118

    • NAID

      130007659771

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Facile Synthesis of Diverse o-Iodoaryl Triflates from o-Silylaryl Triflates by Aluminum-mediated Desilyliodination2019

    • Author(s)
      Yoshida Suguru、Hazama Yuki、Kanemoto Kazuya、Nakamura Yu、Hosoya Takamitsu
    • Journal Title

      Chemistry Letters

      Volume: 48 Issue: 7 Pages: 742-745

    • DOI

      10.1246/cl.190223

    • NAID

      130007675010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Alkynyl Sulfides by Copper-Catalyzed Thiolation of Terminal Alkynes Using Thiosulfonates2019

    • Author(s)
      Kanemoto Kazuya、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Organic Letters

      Volume: 21 Issue: 9 Pages: 3172-3177

    • DOI

      10.1021/acs.orglett.9b00875

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Resonance on the Clickability of Alkenyl Azides in the Strain-promoted Cycloaddition with Dibenzo-fused Cyclooctynes2019

    • Author(s)
      Yoshida Suguru、Goto Sayuri、Nishiyama Yoshitake、Hazama Yuki、Kondo Masakazu、Matsushita Takeshi、Hosoya Takamitsu
    • Journal Title

      Chemistry Letters

      Volume: 48 Issue: 9 Pages: 1038-1041

    • DOI

      10.1246/cl.190400

    • NAID

      130007703048

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of (2,2-Diborylvinyl)arenes by Rhodium-Catalyzed Desulfanylative gem-Diborylation of 2-Arylvinyl Sulfides2019

    • Author(s)
      Uetake Yuta、Isoda Motoyuki、Niwa Takashi、Hosoya Takamitsu
    • Journal Title

      Organic Letters

      Volume: 21 Issue: 13 Pages: 4933-4938

    • DOI

      10.1021/acs.orglett.9b01253

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 3-Thioaryne Intermediates for the Synthesis of Diverse Thioarenes2019

    • Author(s)
      Nakamura Yu、Miyata Yoshihiro、Uchida Keisuke、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Organic Letters

      Volume: 21 Issue: 13 Pages: 5252-5258

    • DOI

      10.1021/acs.orglett.9b01862

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facile Synthesis of Diverse 2,6-Disubstituted Arylsilanes via Silylamination and Silylsulfanylation of Aryne Intermediates Generated from o-Iodoaryl Triflates2019

    • Author(s)
      Nakamura Yu、Ozawa Saki、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Chemistry Letters

      Volume: 48 Issue: 11 Pages: 1296-1299

    • DOI

      10.1246/cl.190573

    • NAID

      130007741802

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Diverse γ-Aryl-β-ketoesters via Aryne Intermediates Generated by C?C Bond Cleavage2019

    • Author(s)
      Uchida Keisuke、Minami Yasunori、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Organic Letters

      Volume: 21 Issue: 22 Pages: 9019-9023

    • DOI

      10.1021/acs.orglett.9b03418

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent Advances in Synthetic Hetaryne Chemistry2019

    • Author(s)
      Nakamura Yu、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      HETEROCYCLES

      Volume: 98 Issue: 12 Pages: 1623-1677

    • DOI

      10.3987/rev-19-917

    • NAID

      40022163326

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Diverse 3-Azido-5-(azidomethyl)benzene Derivatives via Formal C-H Azidation and Functional Group-Selective Transformations2019

    • Author(s)
      Nishiyama Yoshitake、Misawa Yoshihiro、Hazama Yuki、Oya Kazuhiro、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      HETEROCYCLES

      Volume: 99 Issue: 2 Pages: 1053-1072

    • DOI

      10.3987/com-18-s(f)72

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A facile preparation of functional cycloalkynes via an azide-to-cycloalkyne switching approach2019

    • Author(s)
      Yoshida Suguru、Kuribara Tomoko、Ito Harumi、Meguro Tomohiro、Nishiyama Yoshitake、Karaki Fumika、Hatakeyama Yasutomo、Koike Yuka、Kii Isao、Hosoya Takamitsu
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 24 Pages: 3556-3559

    • DOI

      10.1039/c9cc01113g

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Diverse Phenothiazines by Direct Thioamination of Arynes with S-(o-Bromoaryl)-S-methylsulfilimines and Subsequent Intramolecular Buchwald?Hartwig Amination2018

    • Author(s)
      Matsuzawa Tsubasa、Uchida Keisuke、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Chemistry Letters

      Volume: 47 Issue: 7 Pages: 825-828

    • DOI

      10.1246/cl.180304

    • NAID

      130007402803

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Staudinger reaction using 2,6-dichlorophenyl azide derivatives for robust aza-ylide formation applicable to bioconjugation in living cells2018

    • Author(s)
      Meguro Tomohiro、Terashima Norikazu、Ito Harumi、Koike Yuka、Kii Isao、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Chemical Communications

      Volume: 54 Issue: 57 Pages: 7904-7907

    • DOI

      10.1039/c8cc00179k

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expanding the synthesizable multisubstituted benzo[b]thiophenes via 6,7-thienobenzynes generated from o-silylaryl triflate-type precursors2018

    • Author(s)
      Yoshida Suguru、Kuribara Tomoko、Morita Takamoto、Matsuzawa Tsubasa、Morimoto Kazushi、Kobayashi Takuya、Hosoya Takamitsu
    • Journal Title

      RSC Advances

      Volume: 8 Issue: 39 Pages: 21754-21758

    • DOI

      10.1039/c8ra04035d

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient Protection of Organic Azides from Click Reactions with Alkynes by Phosphazide Formation2018

    • Author(s)
      Meguro Tomohiro、Yoshida Suguru、Igawa Kazunobu、Tomooka Katsuhiko、Hosoya Takamitsu
    • Journal Title

      Organic Letters

      Volume: 20 Issue: 13 Pages: 4126-4130

    • DOI

      10.1021/acs.orglett.8b01692

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Arynes by Selective Cleavage of a Carbon?Phosphorus Bond of o-(Diarylphosphinyl)aryl Triflates Using a Grignard Reagent2018

    • Author(s)
      Nishiyama Yoshitake、Kamada Shuhei、Yoshida Suguru、Hosoya Takamitsu
    • Journal Title

      Chemistry Letters

      Volume: 47 Issue: 9 Pages: 1216-1219

    • DOI

      10.1246/cl.180555

    • NAID

      130007472141

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Further enhancement of the clickability of doubly sterically-hindered aryl azides by para-amino substitution2018

    • Author(s)
      Yoshida Suguru、Tanaka Junko、Nishiyama Yoshitake、Hazama Yuki、Matsushita Takeshi、Hosoya Takamitsu
    • Journal Title

      Chemical Communications

      Volume: 54 Issue: 96 Pages: 13499-13502

    • DOI

      10.1039/c8cc05791e

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 遷移金属触媒存在下での炭素ーヘテロ原子結合形成反応を利用したジアジド化合物群の簡便合成法の開発2020

    • Author(s)
      坂田優希、吉田 優、細谷孝充
    • Organizer
      新学術領域研究「反応集積化が導く中分子戦略:高次生物機能分子の創製」第9回成果報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ホスファジド形成を利用した多彩なアジド化合物の保護2020

    • Author(s)
      會見貴宏、目黒友啓、細谷孝充、吉田 優
    • Organizer
      日本化学会第100春季年会(2020)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 環状アルキン保護法の開発と生体分子の化学修飾への応用2019

    • Author(s)
      吉田 優、畠山泰朋、栗原ともこ、伊藤晴海、目黒友啓、西山義剛、唐木文霞、小池悠華、上本紘平、植草秀裕、喜井 勲、細谷孝充
    • Organizer
      第77回有機合成化学協会関東支部シンポジウム(横浜シンポジウム)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 異種アジド基の選択的な利用を鍵とする機能性中分子の迅速合成法の開発2019

    • Author(s)
      細谷孝充
    • Organizer
      新学術領域研究「反応集積化が導く中分子戦略:高次生物機能分子の創製」第8回成果報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アジド化合物とホスフィン類との反応を活用した新しい分子連結法の開発2019

    • Author(s)
      吉田 優、目黒友啓、寺嶌紀和、伊藤晴海、小池悠華、井川和宣、友岡克彦、喜井 勲、細谷孝充
    • Organizer
      第115回有機合成シンポジウム2019年【春】
    • Related Report
      2019 Annual Research Report
  • [Presentation] ペプチド型プラットフォーム分子を用いた逐次クリック反応の開発2019

    • Author(s)
      郡 大輔、西山義剛、藤井 咲、吉田 優、細谷孝充
    • Organizer
      第78回有機合成化学協会関東支部シンポジウム(新津シンポジウム)
    • Related Report
      2019 Annual Research Report
  • [Presentation] リンと銅塩との錯形成を利用した末端アルキン選択的反応による機能性ホスフィン類の簡便合成法の開発2019

    • Author(s)
      寺嶌紀和、目黒友啓、吉田 優、細谷孝充
    • Organizer
      第78回有機合成化学協会関東支部シンポジウム(新津シンポジウム)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 多機能性分子プローブの効率的合成のための新規クリック反応ツールの開発2019

    • Author(s)
      郡 大輔、西山義剛、牧尾直明、藤井 咲、吉田 優、細谷孝充
    • Organizer
      日本化学会第99春季年会(2019)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 多機能性分子プローブ創製を指向した新たなクリック反応ツールの開発2018

    • Author(s)
      郡 大輔、西山義剛、牧尾直明、藤井 咲、吉田 優、細谷孝充
    • Organizer
      第35回有機合成化学セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] 環状アルキンと銀塩および金塩との錯形成を利用した選択的クリック反応の開発2018

    • Author(s)
      安立啓介、目黒友啓、吉田 優、細谷孝充
    • Organizer
      第44回反応と合成の進歩シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Facile Synthesis of Diazido Compounds via Formal C-H Azidation and Functional Group-Selective Conversions2018

    • Author(s)
      Nishiyama Y, Misawa Y, Hazama Y, Oya K, Yoshida S, Hosoya T
    • Organizer
      The 4th International Symposium of Middle Molecular Strategy and The 7th Innovative Area Symposium on Middle Molecular Strategy: Creation of Higher Bio-Functional Molecules by Integrated Synthesis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-01-27  

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