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Control of sulfoxide stereochemistry using visible lights and application to the medicinal drugs.

Research Project

Project/Area Number 19K16454
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionMusashino University (2022)
Tokyo University of Science (2019-2021)

Principal Investigator

Makino Kosho  武蔵野大学, 薬学部, 助教 (40784369)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords光化学 / ラセミ化 / キラルスルホキシド / 光増感剤 / 光 / アルケン / 医薬品 / 安定性 / 光ラセミ化 / スルホキシド / 動的速度論的光学分割法 / 不斉誘起反応
Outline of Research at the Start

本研究では市販の医薬品やその代謝物に含まれるスルホキシドの光エネルギーに対する立体化学の安定性を検討し、ラセミ化の起こる要因を明らかにする。さらに、これに基づき、光を利用した生物活性物質の不斉反応を開発する。本研究は、光に対する医薬品の安定性を確保するための基礎的な知見を得て、これを生物活性物質の不斉合成に応用することで、医療 薬学及び医薬化学分野に貢献する。

Outline of Final Research Achievements

We studied the racemization reaction of sulfoxides and achieved the following results. 1. The rapid photoracemization reaction of enantiopure alkyl aryl sulfoxides using 1 mol% of mol % 2,4,6-triphenylpyrylium tetrafluoroborate (TPT+) was developed and racemization reaction proceeded extremely fast (t1/2 = 2.1 s, 3.19 x 103 M-1. S-1). 2. A recycle photoreactor utilizing deracemization concept, in which a racemate is converted into a pure enantiomer, has been developed and successfully applied to the synthesis of chiral alkyl aryl sulfoxides. The system uses no chiral reagent to obtain the desired enantiomeric form from racemic sulfoxides in high yield and high optical purity.

Academic Significance and Societal Importance of the Research Achievements

キラルスルホキシドの立体化学の安定性は高く、150kJ/mol 以上の活性化エネルギーが必要であるため、光学活性なスルホキシドは一般的にラセミ化しないと考えられている。一方で、光照射によりラセミ化する事は知られているものの強力な紫外光源が必要とされ、本成果である可視光照射により高速でラセミ化する事は知られておらず、学術的な意義は高い。また、光とキラルカラムをリサイクルHPLC流路内で行う動的不斉誘起法は不斉源を用いず、所望のキラルスルホキシドを得られるため、医薬品など供給に使用できる可能があるため社会的意義は高い。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results) Presentation (3 results) Book (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Photoisomerization of Sulindac and Ozagrel Hydrochloride by Vitamin B<sub>2</sub> Catalyst Under Visible Light Irradiation2022

    • Author(s)
      Suga Mayuko、Makino Kosho、Tabata Hidetsugu、Oshitari Tetsuta、Natsugari Hideaki、Takahashi Hideyo
    • Journal Title

      Pharmaceutical Research

      Volume: 39 Issue: 3 Pages: 577

    • DOI

      10.1007/s11095-022-03203-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid Photoracemization of Chiral Alkyl Aryl Sulfoxides2021

    • Author(s)
      Makino Kosho、Tozawa Kumi、Tanaka Yuki、Inagaki Akiko、Tabata Hidetsugu、Oshitari Tetsuta、Natsugari Hideaki、Takahashi Hideyo
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 86 Issue: 23 Pages: 17249

    • DOI

      10.1021/acs.joc.1c02320

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Conformational Preference of 2′-Fluoro-Substituted Acetophenone Derivatives Revealed by Through-Space <sup>1</sup>H-<sup>19</sup>F and <sup>13</sup>C-<sup>19</sup>F Spin-Spin Couplings2021

    • Author(s)
      Otake Chinatsu、Namba Takuya、Tabata Hidetsugu、Makino Kosho、Hirano Kiriko、Oshitari Tetsuta、Natsugari Hideaki、Kusumi Takenori、Takahashi Hideyo
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 86 Issue: 6 Pages: 4638

    • DOI

      10.1021/acs.joc.1c00051

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Atropisomeric Properties of N-Acyl/ N-Sulfonyl 5 H-Dibenzo[ b, d]azepin-7(6 H)-ones2021

    • Author(s)
      Namba Takuya、Hotta Mayuno、Tabata Hidetsugu、Makino Kosho、Oshitari Tetsuta、Natsugari Hideaki、Takahashi Hideyo
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 86 Issue: 11 Pages: 7563

    • DOI

      10.1021/acs.joc.1c00594

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conformational properties and M<sub>1</sub> antimuscarinic activity of 4-substituted pirenzepine/telenzepine analogues2020

    • Author(s)
      Takahashi Hideyo、Kanase Yuki、Makino Kosho、Yoshinaga Takashi、Tabata Hidetsugu、Oshitari Tetsuta、Natsugari Hideaki
    • Journal Title

      HETEROCYCLES

      Volume: 101 Issue: 1 Pages: 273

    • DOI

      10.3987/com-19-s(f)23

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural Basis of Beneficial Design for Effective Nicotinamide Phosphoribosyltransferase Inhibitors2020

    • Author(s)
      Tanuma Sei-ichi、Katsuragi Kiyotaka、Oyama Takahiro、Yoshimori Atsushi、Shibasaki Yuri、Asawa Yasunobu、Yamazaki Hiroaki、Makino Kosho、Okazawa Miwa、Ogino Yoko、Sakamoto Yoshimi、Nomura Miyuki、Sato Akira、Abe Hideaki、Nakamura Hiroyuki、Takahashi Hideyo、Tanuma Nobuhiro、Uchiumi Fumiaki
    • Journal Title

      Molecules

      Volume: 25 Issue: 16 Pages: 3633-3633

    • DOI

      10.3390/molecules25163633

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional induction of cystathionine γ-lyase, a reactive sulfur-producing enzyme, by copper diethyldithiocarbamate in cultured vascular endothelial cells2020

    • Author(s)
      Tomoya Fujie, Akane Takahashi, Musubu Takahashi, Takato Hara, Asuka Soyama, Kosho Makino, Hideyo Takahashi, Chika Yamamoto, Yoshito Kumagai, Hiroshi Naka and Toshiyuki Kaji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 17 Pages: 6053-6053

    • DOI

      10.3390/ijms21176053

    • NAID

      120007163377

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemoselective Demethylation of Methoxypyridine2019

    • Author(s)
      Kosho, Makino; Yumi, Hasegawa; Takahide, Inoue; Koji, Araki; Hidetsugu, Tabata; Tetsuta, Oshitari; Kiyomi, Ito; Hideaki, Natsugari; Hideyo, Takahashi;
    • Journal Title

      SYNLETT

      Volume: 30 Issue: 8 Pages: 951

    • DOI

      10.1055/s-0037-1612427

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elucidation of the conformational properties of 3-pyridinoyl indoles as intermediates of cannabimimetics2019

    • Author(s)
      Takahashi Hideyo、Araki Koji、Tabata Hidetsugu、Makino Kosho、Ujiie Ryohei、Sezaki Kohei、Nakayama Hiroshi、Oshitari Tetsuta、Natsugari Hideaki
    • Journal Title

      HETEROCYCLES

      Volume: 98 Issue: 10 Pages: 1423

    • DOI

      10.3987/com-19-14161

    • NAID

      40022091342

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] スルホキシドの高速光ラセミ化反応を利用したキラルなスルホキシドの供給法の開発2021

    • Author(s)
      牧野宏章、斗沢紅美、田中優希、稲垣昭子、田畑英嗣、忍足鉄太、夏苅英昭、高橋秀依
    • Organizer
      第47回反応と合成の進歩シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 光ラセミ化を利用したキラルスルホキシドの収束的供給法の確立2021

    • Author(s)
      田中優希、牧野宏章、田畑英嗣、忍足鉄太、夏苅英昭、高橋秀依
    • Organizer
      第141年会 日本薬学年会
    • Related Report
      2020 Research-status Report
  • [Presentation] S-オキシド誘導体の光によるラセミ化現象とその応用2019

    • Author(s)
      牧野宏章1、顧嘉悦1、木村翼2、田畑英嗣2、忍足鉄太2、夏苅英昭3、高橋秀依1
    • Organizer
      第37回メディシナルケミストリーシンポジウム
    • Related Report
      2019 Research-status Report
  • [Book] 注射薬調剤監査マニュアル 20232022

    • Author(s)
      石井伊都子、注射薬調剤監査マニュアル編集委員会
    • Total Pages
      950
    • Publisher
      エルゼビア・ジャパン
    • ISBN
      9784860347956
    • Related Report
      2022 Annual Research Report
  • [Book] 注射薬調剤監査マニュアル 20212020

    • Author(s)
      石井 伊都子、注射薬調剤監査マニュアル編集委員会
    • Total Pages
      800
    • Publisher
      エルゼビア・ジャパン
    • ISBN
      9784860343521
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] エナンチオマー調製システム及びエナンチオマー調製システム用光照射装置2021

    • Inventor(s)
      高橋秀依、牧野宏章、金丸国夫
    • Industrial Property Rights Holder
      高橋秀依、牧野宏章、金丸国夫
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-032905
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] スルホキシド化合物のエナンチオマー調製方法及び調製システム2020

    • Inventor(s)
      高橋秀依, 牧野宏章, 顧嘉悦, 田中優希
    • Industrial Property Rights Holder
      高橋秀依, 牧野宏章, 顧嘉悦, 田中優希
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas

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Published: 2019-04-18   Modified: 2024-01-30  

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