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Synthetic Study of Polycyclic Natural Alkaloids and Application to Drug Development

Research Project

Project/Area Number 25293001
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Chemical pharmacy
Research InstitutionChiba University

Principal Investigator

NISHIDA ATSUSHI  千葉大学, 大学院薬学研究院, 教授 (80130029)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywordsアルカロイド / ランドリン / グランジロジン / シゾコムニン / イルシナールA / マンザミンA / アレルギー性肺真菌症 / 抗メラノーマ薬 / 不斉全合成 / Diels-Alder反応 / カルバゾール / カルバゾマイシン / 全合成 / 構造活性相関研究 / 不斉脱プロトン化反応 / ランドリンB / グランジロジンC / ラピディレクチンB / ミノビンシン / コプシアアルカロイド / ランドリンB / ビニルインドール / 希土類触媒 / ストリキニーネ / スエヒロタケ / 天然物合成 / 悪性黒色腫 / シクロプロパン / 不斉Diels-Alder反応 / ヒドロカルバゾール
Outline of Final Research Achievements

Syntheses of several polycyclic alkaloids have been studied. 1) Structurally unique Kopsia alkaloids, lundurines, which have a cyclopropane-fused indoline skeleton, and grandilodine C have been synthesized firstly. 2) Total synthesis of minovincine was achieved by catalytic asymmetric Diels-Alder reaction of (siloxyvinyl)indole and substituted alkenes using chiral holmium catalyst. A core skeleton of strychnine was prepared by diastereoselective Diels-Alder reaction under catalytic conditions using thulium or scandium salt. 3) Highly efficient total synthesis of scizocommunin has been achieved and its structure was confirmed synthetically. Biological activity of scizocommunin was also studied and it showed moderate antiproliferative activity. 3) A manzamine alkaloid, ircinal A has been synthesized in optically active form using furane-iminiumu cation cyclization (FIC). Formal total synthesis of manzamine A has been accomplished.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (48 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Acknowledgement Compliant: 9 results,  Open Access: 3 results) Presentation (28 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Catalytic and Enantioselective Diels-Alder Reaction of Silyloxydiene That Incorporates a Pyrrolidine Ring, and Its Application to the Construction of Chiral Tri- and Tetracyclic Skeletons2017

    • Author(s)
      Shinji Harada, Saki Nakashima, Wataru Yamada, Takahiro Morikawa, Atsushi Nishida
    • Journal Title

      Heterocycles

      Volume: 95 Issue: 2 Pages: 872-893

    • DOI

      10.3987/com-16-s(s)56

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Construction of Optically Active Isotwistanes and Aminocyclitols Using Chiral Cyclohexadiene as a Common Intermediate2016

    • Author(s)
      Shinji Harada, Kexin Li, Ryuto Kino, Takuya Takeda, Chia-Hsien Wu, Shiharu Hiraoka, and Atsushi Nishida,
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 10 Pages: 1474-1483

    • DOI

      10.1248/cpb.c16-00431

    • NAID

      130005598056

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Total Syntheses of (+)-Grandilodine C and (+)-Lapidilectine B; Determination of their Absolute Stereochemistry2016

    • Author(s)
      Nakajima, M.; Arai, S.; Nishida, A.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 55 Issue: 10 Pages: 3473-3476

    • DOI

      10.1002/anie.201510561

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Furan-Iminium Cation Cyclization (FIC) in A Total Synthesis of Manzamine Alkaloids and A Formal Total Synthesis of Manzamine A. J. Antibiotics, 2016, xx, xxx-xxx. DOI: 102016

    • Author(s)
      A. Nishida, A.; Tokumaru, K.; Ohfusa, T.; Arai, S.
    • Journal Title

      J. Antibiotics

      Volume: 69 Issue: 4 Pages: 340-343

    • DOI

      10.1038/ja.2016.24

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric Total Synthesis of (-)-Lundurine B and Determination of Its Absolute Stereochemistry2015

    • Author(s)
      Nakajima, M.; Arai, S.; Nishida, A.
    • Journal Title

      Chem. Asian J.

      Volume: 10 Issue: 4 Pages: 1065-1070

    • DOI

      10.1002/asia.201403407

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Chiral Holmium Complex-Catalyzed Synthesis of Hydrocarbazole from Siloxyvinylindole and Its Application to the Enantioselective Total Synthesis of (-)-Minovincine2015

    • Author(s)
      Takahiro Morikawa, Shinji Harada, Atsushi Nishida
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 80 Issue: 17 Pages: 8859-8867

    • DOI

      10.1021/acs.joc.5b01393

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Catalytic Asymmetric Nazarov Cyclization of Heteroaryl Vinyl Ketones through a Crystallographically Defined Chiral Dinuclear Nickel Complex2015

    • Author(s)
      Takuya Takeda, Shinji Harada, and Atsushi Nishida.
    • Journal Title

      Organic Letters

      Volume: 17 Issue: 21 Pages: 5184-5187

    • DOI

      10.1021/acs.orglett.5b02497

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Catalytic and Enantioselective Synthesis of A Key Intermediate of the MCHr1 Antagonist AMG 0762015

    • Author(s)
      Shinji Harada, Haruka Ishii, Daisuke Shirasaki, Atsushi Nishida
    • Journal Title

      Heterocycles

      Volume: 90 Issue: 2 Pages: 967-977

    • DOI

      10.3987/com-14-s(k)64

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A Concise and Versatile Synthesis of Alkaloids from Kopsia tenuis: Total Synthesis of (±)-Lundurine A and B2014

    • Author(s)
      Shigeru Arai, Masaya Nakajima, Atsushi Nishida
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 53 Issue: 22 Pages: 5569-5572

    • DOI

      10.1002/anie.201400464

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Stereoselective synthesis of chiral hydrocarbazoles via the catalytic Diels-Alder reaction of siloxyvinylindole and cyclic Z-olefin2014

    • Author(s)
      Yoshida, K.; Morikawa, T.; Yokozuka, N.; Harada, S.; Nishida, A.
    • Journal Title

      Tetrahedron Letter

      Volume: 55 Issue: 50 Pages: 6907-6910

    • DOI

      10.1016/j.tetlet.2014.10.106

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] アレルギー性気管支肺真菌症2014

    • Author(s)
      西田篤司、亀井克彦
    • Journal Title

      呼吸と循環

      Volume: 62 Pages: 769-775

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis of (±)-lundurine B2014

    • Author(s)
      Hoshi, M., Kaneko, O., Nakajima, M., Arai, S., Nishida, A.
    • Journal Title

      Organic Letters

      Volume: 16 Issue: 3 Pages: 768-771

    • DOI

      10.1021/ol4034786

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Catalytic and Enantioselective Diels-Alder Reaction of Electron-Rich Dienes Using Chiral Rare-Earth Metal Complex2013

    • Author(s)
      Harada, S., Morikawa, T., Hiraoka, S., Nishida, A.
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 71 Issue: 8 Pages: 818-829

    • DOI

      10.5059/yukigoseikyokaishi.71.818

    • NAID

      10031191018

    • ISSN
      0037-9980, 1883-6526
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis of schizocommunin and revision of its structure2013

    • Author(s)
      Uehata, K., Kimura, N., Hasegawa, K., Arai, S., Nishida, M., Hosoe, T., Kawai, K.-I., Nishida, A.
    • Journal Title

      Journal of Natural Products

      Volume: 76 Issue: 11 Pages: 2034-2039

    • DOI

      10.1021/np400263f

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chiral holmium complex-catalyzed Diels-Alder reaction of silyloxyvinylindoles: Stereoselective synthesis of hydrocarbazoles2013

    • Author(s)
      Harada, S., Morikawa, T., Nishida, A.
    • Journal Title

      Organic Letters

      Volume: 15 Issue: 20 Pages: 5314-5317

    • DOI

      10.1021/ol402559z

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] (-)-minovincineの全合成と可視光酸化還元触媒を用いる二重結合修飾反応の開発2017

    • Author(s)
      森川貴裕、原田真至、西田篤司
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Ni触媒による[2+2+2]環化付加反応の開発2017

    • Author(s)
      井崎亜利紗、荒井秀、西田篤司
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Catalytic and Enantioselective Nazarov Cyclization through a Chiral Dinuclear Nickel Complex2017

    • Author(s)
      Shinji Harada, Takuya Takeda, Atsushi Nishida
    • Organizer
      日本化学会 第97春季年会2017
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(東京)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Chirality transfer of optical active allenes through nickel-catalyzed hydrocyanation and its application to hydrocyanative cyclization2017

    • Author(s)
      Yuka Amako, Shigeru Arai, Atsushi Nishida
    • Organizer
      日本化学会 第97春季年会2017
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(東京)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Enamtioselective Deils-Alder Reaction Using Chiral Holmium Complex, and the Construction of Nitrogen-Containing Polycyclic Skeleton2017

    • Author(s)
      Saki Nakashima, Wataru Yamada, Takahiro Morikawa, Shinji Harada, Atsushi Nishida
    • Organizer
      日本化学会 第97春季年会2017
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(東京)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of Chiral Holmium Catalyst for Enantioselective Diels-Alder Reaction2016

    • Author(s)
      Saki Nakashima, Wataru Yamada, Takahiro Morikawa, Shinji Harada, Atsushi Nishida
    • Organizer
      International Symposium on Lanthanide Coordination Chemistry (ISLCC 2016)
    • Place of Presentation
      Aoyama Gakuin University, Sagamihara, Kanagawa, JAPAN
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Total synthesis of polycyclic alkaloids, lundurines, and grandilodine2015

    • Author(s)
      Atsushi Nishida, Masaya Nakajima, Shigeru Arai
    • Organizer
      PACIFICHEM 2015
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Total Syntheses of (+)-Grandilodine C and (+)-Lapidilectine B; Determination of Their Absolute Stereochemistry2015

    • Author(s)
      Atsushi Nishida
    • Organizer
      ICCEOCA-10/ARNCEOCA-1
    • Place of Presentation
      高雄、台湾
    • Year and Date
      2015-11-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ランドリンB及び関連アルカロイドの全合成2015

    • Author(s)
      中島誠也,荒井秀,西田篤司
    • Organizer
      5th CSJフェスタ2015
    • Place of Presentation
      神戸
    • Year and Date
      2015-10-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Danishefsky ジエンとマレイミド誘導体による触媒的不斉Diels-Alder反応の開発2015

    • Author(s)
      江守皓亮,坂本駿,原田真至,西田篤司
    • Organizer
      第59回日本薬学会関東支部大会若手シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] First total Synthesis of Lundurine A and B2014

    • Author(s)
      Atsushi Nishida, Masaki Hoshi, Masaya Nakajima, Shigeru Arai
    • Organizer
      ICCEOCA-9/NICCEOCA-4
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      2014-12-01 – 2014-12-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Stereoselective Synthesis of Hydrocarbazoles via Holmium-Catalyzed Diels-Alder Reaction of Silyloxyvinylindoles, and Its Application to Synthetic Study of Natural Products2014

    • Author(s)
      Atsushi Nishida
    • Organizer
      Vietnam Malaysia International Chemical Congress (VMICC) 2014
    • Place of Presentation
      Hanoi, Vietnam
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Total Synthesis of Polycyclic Alkaloids, Lundurine A and B2014

    • Author(s)
      Atsushi Nishida
    • Organizer
      Malaysian International Chemical Congress (18MICC) Plenary Lecture
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      2014-11-03 – 2014-11-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] コプシアアルカロイド、ランドリン類の全合成2014

    • Author(s)
      西田篤司、中島誠也、星真幸、荒井秀
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知県県民文化ホール
    • Year and Date
      2014-10-15 – 2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 多環性アルカロイド、ランドリン類の全合成2014

    • Author(s)
      西田篤司
    • Organizer
      第58回日本薬学会関東支部大会若手シンポジウム(特別講演)
    • Place of Presentation
      昭和薬科大学
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 触媒的不斉ヒドロカルバゾール合成を基盤とするストリキニーネの全合成研究2014

    • Author(s)
      吉田佳右、森川貴裕、原田真至、西田篤司
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Enantioselective Synthesis of Hydrocarbozoles by Thulium-Catalyzed [4+2]Cycloaddition2013

    • Author(s)
      Harada, Shinji, Morikawa, Takahiro, Nishida, Atsushi
    • Organizer
      43rd Narional Organic Chemistry Symposium
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lundurine類の全合成研究2013

    • Author(s)
      中島誠也、荒井秀、西田篤司
    • Organizer
      第103回有機合成シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Synthetic Study of Polycyclic Alkaloids2013

    • Author(s)
      Nishida, A., Hiraoka, S., Hoshi, M., Nakajima, M.,Arai, S.
    • Organizer
      International Symposium on Olefin Metathesis and Related Chemistry(ISOM XX)
    • Place of Presentation
      奈良
    • Related Report
      2013 Annual Research Report
  • [Presentation] Total Synthesis of Schizocommunin and Revision of Its Structure2013

    • Author(s)
      Nishida, Atsushi, Uehata, Koji, Nishida, Mayumi
    • Organizer
      13th International Conference on the Chemistry of Antibiotics and other bioactive compounds (ICCA-13)
    • Place of Presentation
      山梨
    • Related Report
      2013 Annual Research Report
  • [Presentation] Total Synthesis of Lundurine A2013

    • Author(s)
      Nakajima, Masaya, Arai, Shigeru, Nishida, Atsushi
    • Organizer
      13th International Conference on the Chemistry of Antibiotics and other bioactive compounds (ICCA-13)
    • Place of Presentation
      山梨
    • Related Report
      2013 Annual Research Report
  • [Presentation] LundurineBの全合成2013

    • Author(s)
      星真幸、金子統、荒井秀、西田篤司
    • Organizer
      第104回有機合成シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 全合成にメタセシスを使う2013

    • Author(s)
      西田篤司
    • Organizer
      有機合成化学協会講習会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Total Synthesis of Lundurine A2013

    • Author(s)
      Nakajima, Masaya, Arai, Shigeru, Nishida, Atsushi
    • Organizer
      3rd Junior ICCEOCA 2013
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
  • [Presentation] Z-オレフィンとDanishefskyジエンの触媒的不斉 Diels-Alder 反応の開発

    • Author(s)
      坂本駿、原田真至、西田篤司
    • Organizer
      第65回有機合成化学協会関東支部シンポジウム
    • Place of Presentation
      新潟
    • Related Report
      2013 Annual Research Report
  • [Presentation] 触媒的不斉Diels-Alder反応を用いたメラニン凝集ホルモン受容体アンタゴニストAMG076の合成研究

    • Author(s)
      石井遥、白石大輔、原田真至、西田篤司
    • Organizer
      第66回有機合成化学協会関東支部シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ニッケル触媒によるアレンのヒドロニッケル化を基軸としたシアノ環化反応

    • Author(s)
      天児由佳、荒井秀、西田篤司
    • Organizer
      第66回有機合成化学協会関東支部シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ニッケル触媒を用いるシアノ基導入型3成分カップリング反応の開発

    • Author(s)
      楊曉菲、荒井秀、西田篤司
    • Organizer
      第66回有機合成化学協会関東支部シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Book] The Alkaloids, Volume 78, Total Synthesis of Lundurine and Related Alkaloids: Synthetic Approaches and Strategies2017

    • Author(s)
      Shigeru Arai, Masaya Nakajima, Atsushi Nishida
    • Total Pages
      38
    • Publisher
      Elsevier Inc.
    • Related Report
      2016 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院 薬品合成化学研究室HP

    • URL

      http://www.p.chiba-u.jp/lab/gousei/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 千葉大学大学院薬品合成化学研究室

    • URL

      http://www.p.chiba-u.jp/lab/gousei/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院薬品合成化学研究室

    • URL

      http://www.p.chiba-u.jp/lab/gousei/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 薬品合成化学研究室

    • URL

      http://www.p.chiba-u.ac.jp/lab/gousei/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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