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Divergent synthesis of unsymmetrical polysulfides by the selective activation of sulfur-bonded leaving groups

Research Project

Project/Area Number 22K14687
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 33020:Synthetic organic chemistry-related
Research InstitutionTohoku University

Principal Investigator

Kanemoto Kazuya  東北大学, 薬学研究科, 助教 (90849100)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsジスルフィド / 多様性合成 / 脱離基 / アミノ基 / イミド基 / トリフルオロ酢酸 / アリルシラン / 芳香族求電子置換反応 / アズラクトン / ペプチド / ポリスルフィド / 求電子的チオ化 / チオ化試薬
Outline of Research at the Start

多数の硫黄原子が連続した構造を持つポリスルフィド類は,様々な応用研究が期待されている有用な化合物群である.一方で,その合成の難しさ故にこれらの応用研究はゆっくりとしか進展してきていなかった.これに対して本研究課題では,「硫黄原子上の2つの脱離基の反応性を制御して使い分ける」という,新たなアプローチを提案する.具体的には,硫黄原子上に2つの脱離基を配置した新たなプラットフォーム分子を開発し,これに対して2つの炭素置換基を集積的に導入することで,短段階で多彩な置換基の組み合わせのポリスルフィドを合成できる基盤を整備し,幅広い分野への貢献を目指す.

Outline of Final Research Achievements

Disulfide bonds are prevalent in diverse fields, including medicinal chemistry, food chemistry, and materials science. Despite their wide applications, the synthesis of unsymmetrical disulfides is challenging because conventional methods tend to provide a mixture of symmetrical and unsymmetrical disulfides. To address this issue, we developed a new bilateral disulfurating reagent, N-(morpholine-4-dithio)phthalimide. This reagent has amino and imide leaving groups that can be orthogonally transformed. Under acidic conditions, the amino leaving group undergoes selective protonation and thus can be displaced by various carbon nucleophiles, such as allyl trimethylsilanes, alkynyl silanes, and electron-rich arenes. Meanwhile, the remaining phthalimide moiety is substituted by amines, thiols, and azlactones under basic or neutral conditions. The combination of these transformations provides access to diverse unsymmetrical disulfides through two C-S bond-forming reactions.

Academic Significance and Societal Importance of the Research Achievements

ジスルフィド化合物は,多彩な生物活性天然物に含まれることに加え,環状ペプチドの構築,機能性ポリマーやリチウム電池電極への利用など,様々な応用研究が期待される有用な化合物群である.その一方で,置換基導入の選択性の低さや,置換基のスクランブルなどにより,非対称なジスルフィドの精密合成は困難であった.本研究課題で開発した手法は,独自に開発したジスルフィドプラットフォーム分子の両側に多彩な置換基を選択的に導入できることから,自在な置換基の組み合わせを有する非対称ジスルフィドの短段階精密合成を可能とし,上記の応用研究を強く後押しするものと期待される.

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (49 results)

All 2024 2023 2022 Other

All Journal Article (17 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 6 results) Presentation (31 results) (of which Int'l Joint Research: 7 results) Remarks (1 results)

  • [Journal Article] Amino- and Alkoxybenziodoxoles: Facile Preparation and Use as Arynophiles2024

    • Author(s)
      Kanemoto Kazuya、Yoshimura Ken、Ono Koki、Ding Wei、Ito Shingo、Yoshikai Naohiko
    • Journal Title

      ChemRxiv

      Volume: -

    • DOI

      10.26434/chemrxiv-2023-kzh7p-v2

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Carboiodanation of Arynes: Organoiodine(III) Compounds as Nucleophilic Organometalloids2024

    • Author(s)
      Arakawa Chisaki、Kanemoto Kazuya、Nakai Katsuya、Wang Chen、Morohashi Shunya、Kwon Eunsang、Ito Shingo、Yoshikai Naohiko
    • Journal Title

      Journal of the American Chemical Society

      Volume: 146 Issue: 6 Pages: 3910-3919

    • DOI

      10.1021/jacs.3c11524

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] N‐Terminal‐Specific Dual Modification of Peptides through Copper‐Catalyzed [3+2] Cycloaddition2024

    • Author(s)
      Machida Haruka、Kanemoto Kazuya
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 63 Issue: 12

    • DOI

      10.1002/anie.202320012

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] N‐Terminal‐Specific Dual Modification of Peptides through Copper‐Catalyzed [3+2] Cycloaddition2024

    • Author(s)
      Machida Haruka、Kanemoto Kazuya
    • Journal Title

      Angewandte Chemie

      Volume: 136 Issue: 12

    • DOI

      10.1002/ange.202320012

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Construction of Diverse Pyrrolidine-Based Skeletons through the Ag-Catalyzed Stereoselective Addition?Elimination Reaction of Azomethine Ylides with Nitroallyl Acetates2024

    • Author(s)
      Ohno Itsuki、Kanemoto Kazuya、Furuya Shohei、Suzuki Yuko、Fukuzawa Shin-ichi
    • Journal Title

      Organic Letters

      Volume: 26 Issue: 9 Pages: 1880-1885

    • DOI

      10.1021/acs.orglett.4c00184

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amino‐ and Alkoxybenziodoxoles: Facile Preparation and Use as Arynophiles2024

    • Author(s)
      Kanemoto Kazuya、Yoshimura Ken、Ono Koki、Ding Wei、Ito Shingo、Yoshikai Naohiko
    • Journal Title

      Chemistry A European Journal

      Volume: - Issue: 29

    • DOI

      10.1002/chem.202400894

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zinc‐Mediated Diastereoselective Annulation of Cyclopropanols with Alkylidenemalononitriles via Enolized Homoenolate2023

    • Author(s)
      Tsukiji Kento、Hayakawa Takeru、Kanemoto Kazuya、Yoshikai Naohiko
    • Journal Title

      Asian Journal of Organic Chemistry

      Volume: 12 Issue: 5

    • DOI

      10.1002/ajoc.202300114

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carboiodanation of arynes: Organoiodine(III) compounds as nucleophilic organometalloids2023

    • Author(s)
      Arakawa Chisaki、Kanemoto Kazuya、Nakai Katsuya、Wang Chen、Morohashi Shunya、Kwon Eunsang、Ito Shingo、Yoshikai Naohiko
    • Journal Title

      ChemRxiv

      Volume: -

    • DOI

      10.26434/chemrxiv-2023-knrnb-v2

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Cationic Iridium‐Catalyzed Decarboxylation of Aromatic Carboxylic Acids2023

    • Author(s)
      Nonami Reina、Kishino Yu、Yamasaki Tomokazu、Kanemoto Kazuya、Iwai Kento、Nishiwaki Nagatoshi、Shibatomi Kazutaka、Shirai Tomohiko
    • Journal Title

      Chemistry An Asian Journal

      Volume: 18 Issue: 17

    • DOI

      10.1002/asia.202300533

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amination of <i>N</i>-(Organodithio)phthalimides for the Modular Synthesis of Aminodisulfides2023

    • Author(s)
      Asanuma Hayato、Kanemoto Kazuya
    • Journal Title

      Organic Letters

      Volume: 26 Issue: 2 Pages: 438-443

    • DOI

      10.1021/acs.orglett.3c03419

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Hydroxyallylation of Cyclopropenes with Cyclopropanols via NHC Catalysis of Transient Organozinc Species2023

    • Author(s)
      Tsukiji Kento、Matsumoto Arimasa、Kanemoto Kazuya、Yoshikai Naohiko
    • Journal Title

      ChemRxiv

      Volume: -

    • DOI

      10.26434/chemrxiv-2023-hch07-v2

    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] Chiral Silver Complex-Catalyzed Asymmetric Conjugate Addition of 1-Pyrroline-5-Carbonitrile to α-Enones2023

    • Author(s)
      Araki Haruna、Furuya Shohei、Kanemoto Kazuya、Fukuzawa Shin-ichi
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 88 Issue: 2 Pages: 924-932

    • DOI

      10.1021/acs.joc.2c02315

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] <i>N</i> ‐(Morpholine‐4‐dithio)phthalimide: A Shelf‐Stable, Bilateral Platform Molecule Enabling Access to Diverse Unsymmetrical Disulfides**2023

    • Author(s)
      Asanuma Hayato、Kanemoto Kazuya、Watanabe Tokiharu、Fukuzawa Shin‐ichi
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 62 Issue: 18

    • DOI

      10.1002/anie.202219156

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] N-Terminal-selective Cu-catalyzed [3+2] cycloaddition for irreversible assembly of two modules with a peptide2023

    • Author(s)
      Machida Haruka、Kanemoto Kazuya、Fuwa Haruhiko
    • Journal Title

      ChemRxiv

      Volume: -

    • DOI

      10.26434/chemrxiv-2023-sxw2w

    • Related Report
      2022 Research-status Report
  • [Journal Article] exo'-Selective Construction of Spirobipyrrolidines by the Silver-catalyzed Asymmetric [3+2] Cycloaddition of Imino Esters with 4-Benzylidene-2,3-dioxopyrrolidines2022

    • Author(s)
      Shohei Furuya、Kanemoto Kazuya、Fukuzawa Shin-ichi
    • Journal Title

      Chemistry An Asian Journal

      Volume: - Issue: 15

    • DOI

      10.1002/asia.202200239

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diastereoselective Conversion of Cyclopropanols to Cyclopentane-1,3-diols via Aldol Dimerization of Zinc Homoenolates2022

    • Author(s)
      Tsukiji Kento、Sekiguchi Yoshiya、Kanemoto Kazuya、Yoshikai Naohiko
    • Journal Title

      Chemistry Letters

      Volume: 51 Issue: 10 Pages: 1012-1014

    • DOI

      10.1246/cl.220311

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] N-(N-Morpholindithio)phthalimide: A Shelf-Stable, Bilateral Platform Molecule for Accessing Diverse Unsymmetrical Disulfides2022

    • Author(s)
      Asanuma Hayato、Kanemoto Kazuya、Watanabe Tokiharu、Fukuzawa Shin-ichi
    • Journal Title

      ChemRxiv

      Volume: -

    • DOI

      10.26434/chemrxiv-2022-t1xn4

    • Related Report
      2022 Research-status Report
  • [Presentation] アラインのジアゾメチルヨウ素(III)化反応2024

    • Author(s)
      大槻 真也 ,金本 和也 ,吉戒 直彦
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Stereoselective Hydroxyallylation of Cyclopropropenes with Cyclopropanols via NHC Control of Enolized Zinc Homoenolate2024

    • Author(s)
      築地 健人, 松本 有正, 金本 和也, 吉戒 直彦
    • Organizer
      日本化学会第104春期年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Stereoselective Hydroxyallylation of Cyclopropenes via NHC Catalysis of Enolized Homoenolate2024

    • Author(s)
      築地 健人, 金本 和也, 吉戒 直彦
    • Organizer
      2024 Bowei Research Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 位置選択的な1,3-双極子環化付加反応を介したキメラ型ペプチドのモジュラー合成2024

    • Author(s)
      岩田 真輝,吉戒 直彦,金本 和也
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヘキサデヒドロDiels-Alder・アルキニルヨウ素(III)化カスケード反応2024

    • Author(s)
      諸橋 駿矢,周 列錦,金本 和也,吉戒 直彦
    • Organizer
      日本化学会第104春期年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ジチオ環化反応によるジスルフィドを置換基に持つ多彩なヘテロ環の構築2024

    • Author(s)
      鷹見 優月,浅沼 隼人,金本 和也,吉戒 直彦
    • Organizer
      第144回日本薬学年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] N-ジチオフタルイミドとアミンを用いる非対称アミノジスルフィドの合成2024

    • Author(s)
      浅沼 隼人,金本 和也
    • Organizer
      日本化学会第104春期年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Diastereo- and Enantioselective Hydroxyallylation of Cyclopropenes via NHC Catalysis of Zinc Homoenolate2023

    • Author(s)
      築地 健人,金本 和也,吉戒 直彦
    • Organizer
      第52回複素環化学討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Zinc-Mediated Stereoselective Hydroxyallylation of Cyclopropenes with Cyclopropanols2023

    • Author(s)
      築地 健人, 金本 和也, 吉戒 直彦
    • Organizer
      第69回有機金属化学討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Stereoselective Hydroxyallylation of Cyclopropenes via NHC Catalysis of Transient Organozinc Intermediate2023

    • Author(s)
      築地 健人, 金本 和也, 吉戒 直彦
    • Organizer
      令和5年度化学系学協会東北大会及び日本化学会東北支部80周年記念国際会議
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] “Zinc/NHC-Mediated Stereoeselective Hydroxyallylation of Cyclopropenes with Cyclopropanols2023

    • Author(s)
      築地 健人, 金本 和也, 吉戒 直彦
    • Organizer
      東北大学Chemistry Summer School 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] デヒドロアラニンのN末端選択的な[3+2]環化付加反応によるペプチドカップリング2023

    • Author(s)
      岩田 真輝,吉戒 直彦,金本 和也
    • Organizer
      第38回有機合成若手研究者の仙台セミナー
    • Related Report
      2023 Annual Research Report
  • [Presentation] デヒドロアラニンのN末端選択的な双極子環化付加によるピロリジン環へのペプチド導入2023

    • Author(s)
      岩田 真輝,金本 和也,吉戒 直彦
    • Organizer
      第52回複素環化学討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Silver-Catalyzed N-Terminal Selective [3+2] Cycloaddition of Peptides with Dehydroalanine Derivatives2023

    • Author(s)
      岩田 真輝,金本 和也,吉戒 直彦
    • Organizer
      第69回有機金属化学討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] N-Terminal Selective Peptide Coupling via [3+2] Cycloaddition Using Dehydroalanine Derivatives2023

    • Author(s)
      Masaki Iwata, Kazuya Kanemoto, Naohiko Yoshikai
    • Organizer
      令和5年度化学系学協会東北大会および日本化学会東北支部 80周年記念国際会議
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] N-Terminal Selective One-Pot [3+2] Cycloaddition of Peptides with Dehydroalanine Derivatives2023

    • Author(s)
      Masaki Iwata, Kazuya Kanemoto, Naohiko Yoshikai
    • Organizer
      東北大学化学系サマースクール
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Preparation of Diverse Heterocyclic Disulfides via Dithiocyclization2023

    • Author(s)
      Yuzuki Takami, Hayato Asanuma, Kazuya Kanemoto, Naohiko Yoshikai
    • Organizer
      第52回複素環化学討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 新たなジスルフィドビルディング試薬を用いるジスルフィド類の網羅的合成法の開発2023

    • Author(s)
      浅沼 隼人,金本 和也,吉戒 直彦
    • Organizer
      第34回万有札幌シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] 網羅的なジスルフィド合成を目指した新たな試薬の開発2023

    • Author(s)
      浅沼 隼人,金本 和也,吉戒 直彦
    • Organizer
      第35 回万札幌台シンポジウム三地区交流ミニセミナー
    • Related Report
      2023 Annual Research Report
  • [Presentation] 新たなジスルフィドビルディング試薬を用いるジスルフィド類の網羅的合成法の開発2023

    • Author(s)
      浅沼 隼人,金本 和也,吉戒 直彦
    • Organizer
      第34回万有仙台シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] 網羅的なジスルフィド合成を目指した新たな試薬の開発2023

    • Author(s)
      浅沼 隼人,金本 和也,吉戒 直彦
    • Organizer
      第34 回万有仙台シンポジウム三地区交流ミニセミナー
    • Related Report
      2023 Annual Research Report
  • [Presentation] 銀触媒を用いるアゾメチンイリドとデヒドロアラニン誘導体の1,3-双極子環化付加反応2023

    • Author(s)
      岩田真輝、金本和也、吉戒直彦
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ペプチドN末端での1,3-双極子環化付加反応による三成分連結2023

    • Author(s)
      金本和也、町田陽佳、不破 春彦
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] アラインのカルボヨウ素(III)化2023

    • Author(s)
      荒川千紗貴、中居捷哉、伊藤慎庫、Chen Wang、金本和也、吉戒直彦
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Trifluoroacetic acid-mediated desulfurilative sulfonylthiolation of arenes via the selective activation of the amino group of SS-morpholino dithiosulfonate2022

    • Author(s)
      Kazuya Kanemoto、 Koudai Furuhashi、Shin-ichi Fukuzawa
    • Organizer
      29th International Symposium on the Organic Chemistry of Sulfur
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Bilateral Disulfurating Platform Molecule for Accessing Diverse Unsymmetrical Disulfides2022

    • Author(s)
      Hayato Asanuma、Tokiharu Watanabe、Shin-ichi Fukuzawa、Kazuya Kanemoto
    • Organizer
      29th International Symposium on the Organic Chemistry of Sulfur
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 亜鉛ホモエノラートの二量化によるジアステレオ選択的なシクロペンタン1,3-ジオールの合成2022

    • Author(s)
      築地健人、関口義也、金本和也、吉戒直彦
    • Organizer
      第38回有機合成化学セミナー
    • Related Report
      2022 Research-status Report
  • [Presentation] 1,3-双極子環化付加反応を用いた N末端グリシン選択的なペプチドの修飾法2022

    • Author(s)
      町田陽佳、金本和也、不破春彦
    • Organizer
      第48回 反応と合成の進歩シンポジウム
    • Related Report
      2022 Research-status Report
  • [Presentation] イミン形成を経由するペプチド N 末端のワンポット修飾反応の開発2022

    • Author(s)
      町田陽佳、金本和也、不破春彦
    • Organizer
      第 83 回有機合成化学協会関東支部シンポジウム
    • Related Report
      2022 Research-status Report
  • [Presentation] アラインのカルボヨウ素(III)化2022

    • Author(s)
      荒川千紗貴、中居捷哉、金本和也、Chen Wang、吉戒直彦
    • Organizer
      第49回 有機典型元素化学討論会
    • Related Report
      2022 Research-status Report
  • [Presentation] 環状アミノおよびアルコキシヨーダンの合成と反応2022

    • Author(s)
      吉村健、小野光紀、金本和也、吉戒直彦
    • Organizer
      第49回 有機典型元素化学討論会
    • Related Report
      2022 Research-status Report
  • [Remarks] ペプチドのピンポイント修飾を実現 創薬や生命現象の解明への利用に期待

    • URL

      https://www.tohoku.ac.jp/japanese/2024/02/press20240213-02-Peptides.html

    • Related Report
      2023 Annual Research Report

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Published: 2022-04-19   Modified: 2025-01-30  

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