• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Selective transformation of amides for late-stage functionalization

Research Project

Project/Area Number 19K06974
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
Research InstitutionKyoto Pharmaceutical University (2020-2021)
Kyoto University (2019)

Principal Investigator

Kobayashi Yusuke  京都薬科大学, 薬学部, 准教授 (90509275)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsアミド / 糖鎖修飾 / ハロゲン結合 / 後期修飾 / 光反応 / ナイトレン / 有機触媒 / 超原子価ヨウ素 / プロドラッグ / 医薬品シーズ / 触媒 / ペプチドミメティック / ペルフルオロアルキル
Outline of Research at the Start

多様な医薬品シーズを創出するためには、生物活性化合物の効率的な分子変換や修飾・誘導体化が必要である。これまで、比較的反応性の高いアミノ基、メルカプト基、カルボキシル基や水酸基を足掛かりとした修飾反応が主に開発されてきたが、中性のアミドは反応性が乏しいため直截的に化学修飾するのが困難であり、変換する手法も限られているのが現状である。そこで、本申請では医薬品・天然物などの小分子によく見られるだけでなく、抗体などのタンパク質を構成する基本構造でもあるアミドに注目し、アミドの新規分子変換法を開発することで新たな医薬品シーズを効率的に創出することを目的とする。

Outline of Final Research Achievements

Derivatization of biologically active compounds, especially at the late-stage, is one of the most powerful strategy for drug discovery. Although various transformation of relatively reactive amino (-NH2), mercapto (-SH), carboxylic (-COOH), and hydroxyl groups (-OH) have been reported, the neutral amide group (-CONH2) is hard to be derivatized, due to its relatively poor reactivity. In this work, several new methods for the derivatization of amides have been achieved by originally developed catalysts and reagents.

Academic Significance and Societal Importance of the Research Achievements

これまでに報告例のないアミドの直截的な分子変換法を達成することができた。例えば、アミド基しかもたないテモゾロミドのような医薬品のプロドラッグ化が可能となり、医薬品開発を大幅に加速することが期待できる。また、合成の終盤での修飾反応は効率的に多様な誘導体を合成できるため、医薬品の構造活性相関研究に多大に貢献することができる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (35 results)

All 2021 2020 2019 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (17 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results) Remarks (5 results)

  • [Journal Article] Nitro-Substituted Benzaldehydes in the Generation of Azomethine Ylides and Retro-1,3-Dipolar Cycloadditions2021

    • Author(s)
      Taha Ahmed G.、Elboray Elghareeb E.、Kobayashi Yusuke、Furuta Takumi、Abbas-Temirek Hussien H.、Aly Moustafa F.
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 86 Issue: 1 Pages: 547-558

    • DOI

      10.1021/acs.joc.0c02241

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A bench-stable <i>N</i>-trifluoroacetyl nitrene equivalent for a simple synthesis of 2-trifluoromethyl oxazoles2021

    • Author(s)
      Kobayashi Yusuke、Masakado Sota、Murai Takuya、Hamada Shohei、Furuta Takumi、Takemoto Yoshiji
    • Journal Title

      Organic and Biomolecular Chemistry

      Volume: 19 Issue: 30 Pages: 6628-6632

    • DOI

      10.1039/d1ob00947h

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Properties of ortho-t-BuSO2C6H4-Substituted Iodonium Ylides2021

    • Author(s)
      Kimura Tomohiro、Hamada Shohei、Furuta Takumi、Takemoto Yoshiji、Kobayashi Yusuke
    • Journal Title

      Crystals

      Volume: 11 Issue: 9 Pages: 1085-1085

    • DOI

      10.3390/cryst11091085

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Azolium/Hydroquinone Organo‐Radical Co‐Catalysis: Aerobic C?C‐Bond Cleavage in Ketones2021

    • Author(s)
      Nakatsuji Yuya、Kobayashi Yusuke、Masuda Sakyo、Takemoto Yoshiji
    • Journal Title

      Chemistry - A European Journal

      Volume: 27 Issue: 8 Pages: 2633-2637

    • DOI

      10.1002/chem.202004943

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regio- and stereoselective glycosylation of 1,2-O-unprotected sugars using organoboron catalysts2020

    • Author(s)
      Kobayashi Yusuke、Takemoto Yoshiji
    • Journal Title

      Tetrahedron

      Volume: 76 Issue: 30 Pages: 131328-131328

    • DOI

      10.1016/j.tet.2020.131328

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis of 1,1′‐Disaccharides by Organoboron Catalysis2020

    • Author(s)
      Izumi Sanae、Kobayashi Yusuke、Takemoto Yoshiji
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 59 Issue: 33 Pages: 14054-14059

    • DOI

      10.1002/anie.202004476

    • NAID

      120006886553

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A solvent-dependent chirality-switchable thia-Michael addition to α,β-unsaturated carboxylic acids using a chiral multifunctional thiourea catalyst2020

    • Author(s)
      Hayama Noboru、Kobayashi Yusuke、Sekimoto Eriko、Miyazaki Anna、Inamoto Kiyofumi、Kimachi Tetsutaro、Takemoto Yoshiji
    • Journal Title

      Chemical Science

      Volume: 11 Issue: 21 Pages: 5572-5576

    • DOI

      10.1039/d0sc01729a

    • NAID

      120006865701

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mild and Chemoselective Thioacylation of Amines Enabled by the Nucleophilic Activation of Elemental Sulfur2020

    • Author(s)
      Masato Saito, Sho Murakami, Takeshi Nanjo, Yusuke Kobayashi, Yoshiji Takemoto
    • Journal Title

      Journal of the American Chemical Society

      Volume: - Issue: 18 Pages: 8130-8135

    • DOI

      10.1021/jacs.0c03256

    • NAID

      120006876568

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reactions Catalyzed by 2-Halogenated Azolium Salts: From Halogen-Bond Donors to Br?nsted-Acidic Salts2020

    • Author(s)
      Kobayashi Yusuke、Takemoto Yoshiji
    • Journal Title

      Synlett

      Volume: 31 Issue: 08 Pages: 772-783

    • DOI

      10.1055/s-0039-1690815

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Photo-Irradiation-Promoted Aminoetherification of Glycals with N-Acyliminoiodinane and Alcohols2020

    • Author(s)
      Takemoto Yoshiji、Masakado Sota、Kobayashi Yusuke
    • Journal Title

      HETEROCYCLES

      Volume: 101 Issue: 2 Pages: 453-453

    • DOI

      10.3987/com-19-s(f)25

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct Addition of Amides to Glycals Enabled by Solvation‐Insusceptible 2‐Haloazolium Salt Catalysis2019

    • Author(s)
      Nakatsuji Yuya、Kobayashi Yusuke、Takemoto Yoshiji
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 58 Issue: 40 Pages: 14115-14119

    • DOI

      10.1002/anie.201907129

    • NAID

      120006766121

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Divergent and Chemoselective Transformations of Thioamides with Designed Carbene Equivalents2019

    • Author(s)
      Saito Masato、Kobayashi Yusuke、Takemoto Yoshiji
    • Journal Title

      Chemistry A European Journal

      Volume: 25 Issue: 44 Pages: 10314-10318

    • DOI

      10.1002/chem.201902699

    • NAID

      120006712297

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] αおよびβ-N-結合型糖ペプチドの迅速合成2021

    • Author(s)
      山西雅子、中辻雄哉、中寛史、竹本佳司、小林祐輔
    • Organizer
      創薬懇話会 2021 in 京都
    • Related Report
      2021 Annual Research Report
  • [Presentation] アゾリウム塩触媒を用いたグリコシル化反応によるα-およびβ-N-結合型糖ペプチドの合成2021

    • Author(s)
      山西雅子、中辻雄哉、中寛史、竹本佳司、小林祐輔
    • Organizer
      第37回有機合成化学セミナー in 広島
    • Related Report
      2021 Annual Research Report
  • [Presentation] グルコサミンに対するアミドの直接的かつ立体選択的グリコシル化反応2021

    • Author(s)
      山西雅子、中辻雄哉、中寛史、竹本佳司、小林祐輔
    • Organizer
      第50回複素環化学討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Direct Glycosylation of Amides with Glucosamine Derivatives Catalyzed by 2-Halogenated Azolium Salt2021

    • Author(s)
      4.Masako Yamanishi, Yuya Nakatsuji, Hiroshi Naka, Yoshiji Takemoto, Yusuke Kobayashi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アゾリウム塩触媒を用いたグルコサミンに対するアミドの直截的かつ立体選択的グリコシル化反応2021

    • Author(s)
      山西 雅子、中辻 雄哉、小林 祐輔、中 寛史、竹本 佳司
    • Organizer
      日本薬学会第141年会 (オンライン)
    • Related Report
      2020 Research-status Report
  • [Presentation] ゾリウム塩とヒドロキノンを有機ラジカル共触媒として用いた炭素-炭素結合の酸化的開裂 反応の開発2020

    • Author(s)
      中辻 雄哉、小林 祐輔、益田 紗京、竹本 佳司
    • Organizer
      反応と合成の進歩 2020 特別企画シンポジウム (オンライン)
    • Related Report
      2020 Research-status Report
  • [Presentation] 縮環構造内に硫黄を持つ二核ロジウム触媒とアミド型 [7]ヘリセンの合成2020

    • Author(s)
      5)井上拓美、中村梨那、村井琢哉、笹森貴裕、浜田翔平、小林祐輔、古田 巧
    • Organizer
      第70回 日本薬学会 関西支部大会,オンライン開催
    • Related Report
      2020 Research-status Report
  • [Presentation] ビアリールジカルボン酸からのフェナントリジノン誘導体のワンポット合成2020

    • Author(s)
      6)村井琢哉、Yongning Xing、黒川真由、浜田翔平、小林祐輔、川端猛夫、古田 巧
    • Organizer
      第70回 日本薬学会 関西支部大会,オンライン開催
    • Related Report
      2020 Research-status Report
  • [Presentation] カルコゲン結合を介したロジウム二核錯体の配座制御 -立体選択的分子内 CーH 挿入反応への展開-2020

    • Author(s)
      7)村井琢哉、陸 文傑、栗林俊文、森崎一宏、上田善弘、浜田翔平、小林祐輔、笹森貴裕、時任宣博、川端猛夫、古田 巧
    • Organizer
      反応と合成の進歩 2020 特別企画シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] ハロゲン結合及び光励起を利用した糖鎖修飾法の開発2020

    • Author(s)
      小林 祐輔
    • Organizer
      第40回有機合成若手セミナー 明日の有機合成を担う人のために
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Direct N-glycofunctionalization of amides by a newly designed Bronsted acid catalyst2019

    • Author(s)
      usuke Kobayashi, Yuya Nakatsuji, Yoshiji Takemoto
    • Organizer
      The 14th International Conference on Cutting-Edge Organic Chemistry in Asia
    • Related Report
      2019 Research-status Report
  • [Presentation] 2-Haloazolium salt enabled the direct addition of amides to glycals2019

    • Author(s)
      Yuya Nakatsuji, Yusuke Kobayashi, Yoshiji Takemoto
    • Organizer
      The 8th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Related Report
      2019 Research-status Report
  • [Presentation] Design and synthesis of new N-Acyliminoiodinanes and its application to catalyst-free aromatic C-H activation2019

    • Author(s)
      Yusuke Kobayashi, Tomohiro Kimura, Yoshiji Takemoto
    • Organizer
      The 8th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Related Report
      2019 Research-status Report
  • [Presentation] Catalyst-Free Aromatic C-H Amidation Using Newly Designed N-Acyliminoiodinanes2019

    • Author(s)
      Yusuke Kobayashi, Tomohiro Kimura, Yoshiji Takemoto
    • Organizer
      The 27th International Society of Heterocyclic Congress
    • Related Report
      2019 Research-status Report
  • [Presentation] Direct addition of Amides to Glycals Enabled by Solvation-insusceptible 2-Haloazolium Salt Catalysis2019

    • Author(s)
      Yusuke Kobayashi, Yuya Nakatsuji, Yoshiji Takemoto
    • Organizer
      The 27th International Society of Heterocyclic Congress
    • Related Report
      2019 Research-status Report
  • [Presentation] 種々のN-アシルイミノヨージナンの合成とその光励起を経る芳香族C-Hアミノ化反応の開発2019

    • Author(s)
      小林祐輔、木村智弘、竹本 佳司
    • Organizer
      第39回 有機合成若手セミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] 室温で秤量可能なN-アシルナイトレン等価体の開発2019

    • Author(s)
      小林 祐輔、木村 智弘、竹本 佳司
    • Organizer
      第86回 日本分析化学会有機微量分析研究懇談会 第110回 計測自動制御学会力学量計測部会 第36回 合同シンポジウム
    • Related Report
      2019 Research-status Report
  • [Book] 月刊バイオインダストリー「第三の生命鎖「糖鎖」を構築する合成化学~グリコシル化の最前線~」2021

    • Author(s)
      小林祐輔,竹本佳司
    • Total Pages
      9
    • Publisher
      シーエムシー出版
    • Related Report
      2021 Annual Research Report
  • [Remarks] 京都薬科大学薬化学分野HP

    • URL

      https://labo.kyoto-phu.ac.jp/yakka/pg122.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] Publons

    • URL

      https://publons.com/researcher/1610174/yusuke-kobayashi/

    • Related Report
      2020 Research-status Report
  • [Remarks] 研究室HP

    • URL

      https://labo.kyoto-phu.ac.jp/yakka/

    • Related Report
      2020 Research-status Report
  • [Remarks] 旧所属研究室HP

    • URL

      http://orgchem.pharm.kyoto-u.ac.jp/

    • Related Report
      2020 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://orgchem.pharm.kyoto-u.ac.jp/paper/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi