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Efficient Synthesis of Natural Products Having Intriguing Biological Activities Useful for Drug Discovery

Research Project

Project/Area Number 19209001
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionNagasaki University

Principal Investigator

HATAKEYAMA SUSUMI (HATAKEYAMA Susumi)  Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (20143000)

Co-Investigator(Kenkyū-buntansha) ISHIHARA Jun  長崎大学, 大学院・医歯薬学総合研究科, 准教授 (80250413)
TAKAHASHI Keisuke  長崎大学, 大学院・医歯薬学総合研究科, 助教 (60380854)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥43,160,000 (Direct Cost: ¥33,200,000、Indirect Cost: ¥9,960,000)
Fiscal Year 2009: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2008: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2007: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
Keywords有機合成化学 / 全合成 / 天然物 / 創薬リード / グルタミン酸受容体作用化合物 / カイトセファリン / PP2A阻害化合物 / ホストリエシン / ホスラクトマイシン / 抗腫瘍活性化合物 / オキサゾロマイシン / 医療開発リード / サリノスポラミドA / 医薬開発リード / ダイシハーベイン / ネオオキサゾロマイシン
Research Abstract

We have studied on the total synthesis of natural products having intriguing biological activities useful for drug discovery. As a result, we have developed efficient methodologies for the synthesis of dyshiherbaine, a glutamate receptor agonist, phoslactomycin B and fostriecin, PP2A inhibitors, and neooxazolomycin, an antitumor antibiotic. In addition, we have developed a new methodology for the construction of heterocycles which relies on an In(III)-catalyzed Conia-ene reaction, and achieved the total synthesis of salinosporamide A, a proteasome inhibitor.

Report

(5 results)
  • 2009 Annual Research Report   Self-evaluation Report ( PDF )   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (39 results)

All 2009 2008 2007 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (14 results) Book (5 results) Remarks (1 results)

  • [Journal Article] Enantio- and Stereoselective Route to the Phoslactomycin Family of Antibiotics : Formal Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B2009

    • Author(s)
      S.M.Sarkar, E.N.Wanzala, S.Shibahara, K.Takahashi, J.Ishihara, S.Hatakeyama
    • Journal Title

      Chem.Commun.

      Pages: 5907-5909

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enantio- and Stereoselective Route to the Phoslactomycin Family of Antibiotics : Formal Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B2009

    • Author(s)
      S. M. Sarkar, E. N. Wanzala, S. Shibahara, K. Takahashi, J. Ishihara, S. Hatakeyama
    • Journal Title

      Chem.Commun.

      Pages: 5907-5909

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Indium-catalyzed Conia-ene reaction for alkaloid synthesis2009

    • Author(s)
      Susumi Hatakeyama
    • Journal Title

      Pure and Applied Chemistry 81

      Pages: 217-226

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of(+)-Fostriecin and(+)-Phoslactomycin B2009

    • Author(s)
      Setsuya Shibahara
    • Journal Title

      Synthesis

      Pages: 2935-2953

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enantio- and stereoselective route to the phoslactomycin family of antibiotics : formal synthesis of(+)-fostriecin and(+)-phoslactomycin B2009

    • Author(s)
      Shaheen M.Sarkar
    • Journal Title

      Chemical Communication

      Pages: 5907-5909

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Entry to Heterocycles Based on Indium-Catalyzed Conia-Ene Reactions : Asymmetric Synthesis of (-)-Salinosporamide A2008

    • Author(s)
      K.Takahashi, M.Midori, K.Kawano, J.Ishihara, S.Hatakeyama
    • Journal Title

      Angew.Chem.Int.Ed. 47

      Pages: 6244-6246

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric Total Synthesis of (+)-Phoslactomycin B2008

    • Author(s)
      S.Shibahara, M.Fujino, M.Tashiro, K.Takahashi, J.Ishihara, S.Hatakeyama
    • Journal Title

      Org.Lett. 10

      Pages: 2139-2142

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Entry to Heterocycles Based on Indium-Catalyzed Conia-Ene Reactions : Asymmetric Synthesis of (-)-Salinosporamide A2008

    • Author(s)
      K. Takahashi, M. Midori, K. Kawano, J. Ishihara, S. Hatakeyama
    • Journal Title

      Angew.Chem.Int.Ed. 47

      Pages: 6244-6246

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Asymmetric Total Synthesis of (+)-Phoslactomycin B2008

    • Author(s)
      S. Shibahara, M. Fujino, M. Tashiro, K. Takahashi, J. Ishihara, S. Hatakeyama
    • Journal Title

      Org.Lett. 10

      Pages: 2139-2142

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Synthetic studies directed toward kaitocephalin : a highly stereocontrolled route to the right-hand pyrrolidine core2008

    • Author(s)
      Keisuke Takahashi
    • Journal Title

      Synlett

      Pages: 671-674

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric Total Synthesis of(+)-Phoslactomycin B2008

    • Author(s)
      Setsuya Shibahara
    • Journal Title

      Organic Letters 10

      Pages: 2139-2142

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric Synthesis of (-)-Salinosporamide A2008

    • Author(s)
      Keisuske Takahashi
    • Journal Title

      Angewandte Chemie International Edition 47

      Pages: 6244-6246

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric synthesis of (+)-trachyspic acid2008

    • Author(s)
      Kenji Morokuma
    • Journal Title

      Tetrahedron Letters 49

      Pages: 6043-6045

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Highly Stereocontrolled Total Synthesis of Dysiherbaine2007

    • Author(s)
      K.Takahashi, T.Matsumura, J.Ishihara, S.Hatakeyama
    • Journal Title

      Chem.Commun.

      Pages: 4158-4160

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of Neooxazolomycin, E.2007

    • Author(s)
      O.Onyango, J.Tsurumoto, N.Imai, K.Takahashi, J.Ishihara, S.Hatakeyama
    • Journal Title

      Angew.Chem.Int.Ed. 46

      Pages: 6703-6705

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Highly Stereocontrolled Total Synthesis of Dysiherbaine2007

    • Author(s)
      K. Takahashi, T. Matsumura, J. Ishihara, S. Hatakeyama
    • Journal Title

      Chem.Commun.

      Pages: 4158-4160

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of Neooxazolomycin2007

    • Author(s)
      E. O. Onyango, J. Tsurumoto, N. Imai, K. Takahashi, J. Ishihara, S. Hatakeyama
    • Journal Title

      Angew.Chem.Int.Ed. 46

      Pages: 6703-6705

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of Neooxazolomycin2007

    • Author(s)
      Evans Otieno Onyango
    • Journal Title

      Angewandte Chemie International Edition 46

      Pages: 6703-6705

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A highly stereocontrolled total synthesis of dysiherbaine2007

    • Author(s)
      Keisuke Takahashi
    • Journal Title

      Chemical communication

      Pages: 4158-4160

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Enantio- and Stereoselective Route to the Phoslac-tomycin Family of Antibiotics : Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B2009

    • Author(s)
      Shaheen M.Sarkar, Everlyne N.Wanzala, Setsuya Shibahara, Keisuske Takahashi, Jun Ishihara, Susumi Hatakeyama
    • Organizer
      The 11th International Kyoto Conference on New Aspects of Organic Chemistry
    • Place of Presentation
      Kyoto (Japan)
    • Year and Date
      2009-11-11
    • Related Report
      2009 Final Research Report
  • [Presentation] Enantio-and Stereoselective Route to the Phoslactomycin Family of Antibiotics : Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B2009

    • Author(s)
      Shaheen M. Sarkar, Everlyne N. Wanzala, Setsuya Shibahara, Keisuske Takahashi, Jun Ishihara, Susumi Hatakeyama
    • Organizer
      The 11th International Kyoto Conference on New Aspects of Organic Chemistry
    • Place of Presentation
      Kyoto (Japan)
    • Year and Date
      2009-11-11
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Enantio- and Sstereoselective Route to the Phoslactomycin Family of Antibiotics : Synthesis of(+)-Fostriecin and(+)-Phoslactomycin B2009

    • Author(s)
      Shaheen M.Sarkar
    • Organizer
      IKCOC-11
    • Place of Presentation
      京都市
    • Year and Date
      2009-11-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] オキサゾロマイシン類天然物の合成研究2009

    • Author(s)
      江藤康平
    • Organizer
      第51回天然有機化合物討論会
    • Place of Presentation
      名古屋市
    • Year and Date
      2009-10-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] 高度置換アルカロイドの合成 : 発想と展開2008

    • Author(s)
      畑山 範
    • Organizer
      第20回若手研究者のためのセミナー
    • Place of Presentation
      福岡
    • Year and Date
      2008-12-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] PP2A阻害活性天然物PhoslactomycinBの全合成2008

    • Author(s)
      芝原攝也, 藤野正堂, 田代泰理, 高橋圭介, 石原淳, 畑山範
    • Organizer
      第50回天然有機化合物討論会
    • Place of Presentation
      福岡
    • Year and Date
      2008-10-01
    • Related Report
      2009 Final Research Report
  • [Presentation] PP2A阻害活性天然物 Phoslactomycin Bの全合成2008

    • Author(s)
      芝原攝也, 藤野正堂, 田代泰理, 高橋圭介, 石原淳, 畑山範
    • Organizer
      第50回天然有機化合物討論会
    • Place of Presentation
      福岡
    • Year and Date
      2008-10-01
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] New Approach To Heterocycles via Conia-Ene Type Reactions : Synthesis of Salinosporamide A and Neooxazolomycin2008

    • Author(s)
      畑山範
    • Organizer
      The 20th French and Japanese Symposium on Medicinal and Fine Chemistry
    • Place of Presentation
      Bordeaux (France)
    • Year and Date
      2008-09-09
    • Related Report
      2009 Self-evaluation Report 2009 Final Research Report
  • [Presentation] New Approach To Heterocycles via Conia-Ene Type Reactions : Synthesis of Salinosporamide A and Neooxazolomycin2008

    • Author(s)
      Susumi Hatakeyama
    • Organizer
      The 20th French and Japanese Symposium on Medicinal and Fine Chemistry
    • Place of Presentation
      BORDEAUX-Cite Mondiale, France
    • Year and Date
      2008-09-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Indium-catalyzed Conia-Ene Reaction for Alkaloid Synthesis2008

    • Author(s)
      畑山範
    • Organizer
      IUPAC 17th International Conference on Organic Synthesis
    • Place of Presentation
      Daejeon (Korea)
    • Year and Date
      2008-06-26
    • Related Report
      2009 Self-evaluation Report 2009 Final Research Report
  • [Presentation] Indium-catalyzed Conia-Ene Reaction for Alkaloid Synthesis2008

    • Author(s)
      Susumi Hatakeyama
    • Organizer
      IUPAC 17th International Conference on Organic Synthesis
    • Place of Presentation
      Daejeon, Korea
    • Year and Date
      2008-06-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] Dyshiherbaineの効率的立体制御合成2007

    • Author(s)
      高橋 圭介
    • Organizer
      第33回反応と合成の進歩シンポジウム
    • Place of Presentation
      ブリックホール、長崎市
    • Year and Date
      2007-11-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Conia-ene型反応に基づく新規ラクタム構築法:Salinosporamide AとNeooxazolo-mycinの合成2007

    • Author(s)
      高橋圭介, 緑美智子, 石原淳, 畑山範
    • Organizer
      第49回天然有機化合物討論会
    • Place of Presentation
      札幌
    • Year and Date
      2007-09-20
    • Related Report
      2009 Final Research Report
  • [Presentation] Conia-ene 型反応に基づく新規ラクタム構築法 : Salinosporamide A とNeooxazolomycin の合成2007

    • Author(s)
      高橋圭介, 緑美智子, 石原淳, 畑山範
    • Organizer
      第49回天然有機化合物討論会
    • Place of Presentation
      札幌
    • Year and Date
      2007-09-20
    • Related Report
      2009 Self-evaluation Report
  • [Book] 天然物の全合成2000-2008(有機合成化学協会編)2009

    • Author(s)
      畑山範
    • Publisher
      化学同人
    • Related Report
      2009 Final Research Report
  • [Book] 進化を続ける有機触媒(有機合成を革新する第三の触媒)(丸岡啓二編)(7章シンコナアルカロイド触媒を用いた不斉炭素-炭素結合形成反応)2009

    • Author(s)
      畑山範
    • Publisher
      化学同人
    • Related Report
      2009 Final Research Report
  • [Book] 天然物の全合成2000~2008(有機合成化学協会 編)2009

    • Author(s)
      畑山範
    • Publisher
      化学同人
    • Related Report
      2009 Self-evaluation Report
  • [Book] 進化を続ける有機触媒 (有機合成を革新する第三の触媒) (丸岡啓二 編), 7章シンコナアルカロイド触媒を用いた不斉炭素-炭素結合形成反応2009

    • Author(s)
      畑山範
    • Publisher
      化学同人
    • Related Report
      2009 Self-evaluation Report
  • [Book] 創薬をめざす有機合成戦略(進化する医薬品づくり)(宍戸宏造,新藤充編)(9章ビタミンD3誘導体の合成)2007

    • Author(s)
      畑山範
    • Publisher
      化学同人
    • Related Report
      2009 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.ph.nagasaki-u.ac.jp/indexj.html

    • Related Report
      2009 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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