Synthetic Investigation of Biologically Active Natural Products Based on the Development of Highly Stereoselective Reaction

• Project/Area Number: 18390010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Tokyo University of Science
• Principal Investigator: KOBAYASHI Susumu Tokyo University of Science, 薬学部, 教授 (70101102)
• Co-Investigator(Kenkyū-buntansha): NAKAZAKI Atsuo 東京理科大学, 薬学部, 助教 (00366428)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥16,580,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥1,680,000); Fiscal Year 2008: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2006: ¥9,300,000 (Direct Cost: ¥9,300,000)
• Keywords: 全合成 / 不斉合成 / ビニロガス向山アルドール反応 / カフレフンジン / TMC-151C / ディバーシフォリン / 閉環メタセシス / ナフレジンγ / 生物活性物質 / 立体選択的反応

Research Abstract

我々が開発した高立体選択的に進行するビニロガス向山アルドール反応を利用し、カフレフンジン、TMC-151Cの全合成を達成することができた。また、この合成研究の過程で、E-選択的8員環閉環メタセシス反応を見出した。不斉三級アルコールを含む1,2-ジオールの不斉合成法の応用展開としてナフレジンγのコア部分の合成を達成した。一方、不斉三級アルコールを含む1,3-ジオールの立体選択的合成法を利用しディバーシフォリンの全合成を達成することができた。

Research Products

• [Journal Article] A Switch of Facial Selectivities Using a-Heteroatom- substituted Aldehydes in the Vinylogous Mukaiyama Aldol Reaction (2009)
  • Author(s): 篠山麻里子, 城川伸一, 中崎敦夫, 小林進
  • Journal Title: Org.Lett. 11巻 Pages: 1277-1280
  • Peer Reviewed
• [Journal Article] Total Synthesis of (-)-Diversifolin (2009)
  • Author(s): 中村友昭, 坪井和馬, 押田もと子, 野村智子, 中崎敦夫, 小林進
  • Journal Title: Tetrahedron Lett. 50巻 Pages: 2835-2839
  • NAID: 130006998687
  • Peer Reviewed
• [Journal Article] Total Synthesis of (-)-Norzoanthamine (2009)
  • Author(s): 山下大輔
  • Journal Title: Angew. Chemie, Int. Ed., Engl. 48 Pages: 1404-1406
  • Peer Reviewed
• [Journal Article] APhSeCl-Mediated Allylic Oxidation of Prenyl Moiety : A Convenient Method for the Construction of 3-Isopenten-2-ol Unit (2008)
  • Author(s): 中村友昭, 押田もと子, 中崎敦夫, 小林進
  • Journal Title: Chem.Pharm.Bull. 56巻 Pages: 404-406
  • Peer Reviewed
• [Journal Article] Stereocontrolled Total Synthesis of (-)-Gleenol Using Claisen Rearrangement of Sterically Congested Dihydropyran (2008)
  • Author(s): 中崎敦夫
  • Journal Title: Chemistry Letters 37 Pages: 770-771
  • NAID: 10021082601
  • Peer Reviewed
• [Journal Article] Synthesis of Neoechinulin A and Its Derivatives (2008)
  • Author(s): 倉持幸司
  • Journal Title: Synthesis 2008 Pages: 3810-3818
  • Peer Reviewed
• [Journal Article] A PhSeCl-Mediated Allylic Oxidation of Prenyl Moiety: A Convenient Method for the Construction of 3-Isopenten-2-ol Unit (2008)
  • Author(s): Tomoaki Nakamura, Motoko Oshida, Atsuo Nakazaki, Susumu Kobayashi
  • Journal Title: Chemical and Pharmaceutical Bulletin 56 Pages: 404-406
  • NAID: 110006622652
  • Peer Reviewed
• [Journal Article] Khafrefungin Using Highly Stereo-selective Vinylogous Mukaiyama Aldol Reaction (2007)
  • Author(s): 城川伸一, 篠山麻里子, 大井勲, 細川誠二郎, 中崎敦夫, 小林進, Total Synthesis
  • Journal Title: Org.Lett. 9巻 Pages: 849-852
  • Peer Reviewed
• [Journal Article] Synthetic Study of Diversifolin : The Construction of 11-Oxabicyclo [6.2.1] undec-3-ene Core using Ring Closing Metathesis (2007)
  • Author(s): 中村友昭, 押田もと子, 野村智子, 中崎敦夫, 小林進
  • Journal Title: Org.Lett. 9巻 Pages: 5533-5536
  • Peer Reviewed
• [Journal Article] Synthetic Study of Diversifolin: The Construction of 11-Oxabicyclo[6.2.1]undec-3-ene Core using Ring Closing Metathesis (2007)
  • Author(s): Tomoaki Nakamura, Motoko Oshida, Tomoko Nomura, Atsuo Nakazaki, Susumu Kobayashi
  • Journal Title: Organic Letters 26 Pages: 5533-5536
  • Peer Reviewed
• [Journal Article] Total Synthesis of Khafrcfungin Using Highly Stereoselective Vinylogous Mukaiyama Aldol Reaction (2007)
  • Author(s): Shin-ichi Shirokawa, Mariko Shinoyama, Isao Ooi, Seijiro Hosokawa, Atsuo Nakazaki, Susumu Kobayashi
  • Journal Title: Organic Letters 9巻5号 Pages: 849-852
• [Journal Article] Synthesis of Convolutamydines B and E (2006)
  • Author(s): 中村友昭, 城川伸一, 細川誠二郎, 中崎敦夫, 小林進, Enantioselective Total
  • Journal Title: Org.Lett. 8巻 Pages: 677-679
  • Peer Reviewed
• [Journal Article] Enantioselective Total Synthesis of Convolutamydincs B and E (2006)
  • Author(s): T.Nakamura, S.Shirokawa, S.Hosokawa, A.Nakazaki, S.Kobayashi
  • Journal Title: Organic Letters 8巻4号 Pages: 677-679
• [Journal Article] Total synthesis of (-)-neocchinulin A (2006)
  • Author(s): T.Aoki, S.Kamisuki, M.Kimoto, K.Onishi, Y.Takakusagi, K.Kuramochi, Y.Takeda, A.Nakazaki, K.Kuroiwa, T.Ohuchi, F.Sugawara, T.Arai, S.Kobayashi
  • Journal Title: Synlctt, 2006 (5), 677-680. 5号 Pages: 677-680
• [Journal Article] Synthesis and absolute configuration of (+)-pscudodcflectusin : structural revision of aspergione B (2006)
  • Author(s): F.Saito, K.Kuramochi, A.Nakazaki, Y.Mizushina, F.Sugawara, S.Kobayashi
  • Journal Title: Euro J. Org. Chem. 21号 Pages: 4796-4799
• [Journal Article] Total Synthesis and Determination of the Relative and Absolute Stereochemistry of the Antitumor Antibiotic, PD 113,271 (2006)
  • Author(s): T.Takeuchi, K.Kuramochi, S.Kobayashi, F.Sugawara
  • Journal Title: Organic Letters 8巻23号 Pages: 5307-5310
• [Presentation] Total Synthesis of Diversifolin, Inhibitor of NF-kB-DNA (2009)
  • Author(s): 中村友昭, 坪井和馬, 押田もと子, 中崎敦夫, 小林進
  • Organizer: 10th Tetrahedron Symposium
  • Place of Presentation: フランス
• [Presentation] 不斉クロチル化反応を用いた Diversifolin の全合成 (2009)
  • Author(s): 坪井和馬, 中村友昭, 押田もと子, 野村智子, 中崎敦夫, 鈴木孝洋, 小林進
  • Organizer: 第44回天然物談話会
  • Place of Presentation: つくば
• [Presentation] TMC-151Cの全合成を日指したE選択的8員環形成RCM反応の開発 (2009)
  • Author(s): 松井亮介, 瀬戸健太郎, 藤田和弘, 中崎敦夫, 鈴木孝洋, 小林進
  • Organizer: 第44回天然物談話会
  • Place of Presentation: つくば
• [Presentation] Total Sunthesis of Diversifolin (2008)
  • Author(s): 坪井和馬, 中村友昭, 押田もと子, 中崎敦夫, 小林進
  • Organizer: 5th Symposium on Chemical Approaches to Chirality
  • Place of Presentation: 東京
  • Year and Date: 2008-12-01
• [Presentation] Norzoanthamineの全合成 (2008)
  • Author(s): 小林 進
  • Organizer: 第50回天然有機化合物討論会
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-02
• [Presentation] ディバーシフォリンの合成研究 : 11-オキサビシクロ [6.2.1] ウンデセン骨格の構築 (2008)
  • Author(s): 中村友昭, 押田もと子, 坪井和馬, 中崎敦夫, 小林進
  • Organizer: 日本薬学会128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] 遠隔不斉誘導とケイ素テザーによる閉環メタセシスを鍵反応とした抗腫瘍活性物質TMC-151Cの合成研究 (2008)
  • Author(s): 松井亮介, 佐藤優奈, 中崎敦夫, 小林進
  • Organizer: 日本薬学会128
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] TMC-151Cのアグリコンの収束的合成 (2008)
  • Author(s): 松井亮介, 佐藤優奈, 中崎敦夫, 小林進
  • Organizer: 第43回 天然物化学談話会
  • Place of Presentation: 大阪
• [Presentation] Synthesis of Polyketide Antibiotics, Khafrefungin and TMC-151C, By Highly Diastereoselective Vinylogous Mukaiyama Aldol Reaction (2008)
  • Author(s): 城川伸一, 松井亮介, 細川誠二郎, 中崎敦夫, 小林進
  • Organizer: XXth French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: フランス
• [Presentation] NF-κB阻害物質ディバーシフォリンの全合成 (2008)
  • Author(s): 中村友昭, 押田もと子, 坪井和馬, 中崎敦夫, 小林進
  • Organizer: 第34回反応と合成の進歩シンポジウム
  • Place of Presentation: 京都
• [Presentation] 遠隔不斉誘導と閉環メタセシスを鍵反応として抗腫瘍性物質TMC-151Cの全合成研究 (2008)
  • Author(s): 松井亮介, 佐藤優奈, 瀬戸健太郎, 中崎敦夫, 小林進
  • Organizer: 第94回有機合成シンポジウム
  • Place of Presentation: 東京
• [Presentation] Development of Highly Stereo-selective Vinylogous Mukaiyama Aldol Reaction and Application to Natural Product Synthesis (2007)
  • Author(s): 小林進
  • Organizer: International Synpo-sium on Catalyst and Fine Chemicals 2007
  • Place of Presentation: シンガポール
  • Year and Date: 2007-12-18
• [Presentation] 遠隔不斉誘導を鍵反応としたポリケチド構造を有する抗腫瘍性物質TMC-151Cの全合成研究 (2007)
  • Author(s): 松井亮介, 佐藤優奈, 中崎敦夫, 小林進
  • Organizer: 第54回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 新潟
  • Year and Date: 2007-12-01
• [Presentation] Synthetic Study of TMC-151C : The Construction of Aglycon Part Utilizing Remote Asymmetric Induction (2007)
  • Author(s): 松井亮介, 佐藤優奈, 中崎敦夫, 小林進
  • Organizer: 3rd Symposium on Chemical Approach to Chirality
  • Place of Presentation: 東京
  • Year and Date: 2007-11-15
• [Presentation] Highly Stereoselective Vinylogous Mukaiyama Aldol Reaction and Application to Natural Product Synthesis (2007)
  • Author(s): 中崎敦夫, 城川伸一, 篠山麻里子, 中村友昭, 細川誠二郎, 小林進
  • Organizer: 19th French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: 富山
• [Presentation] NFKB活性阻害物質 Diversifolin の合成研究 (2007)
  • Author(s): 中村友昭, 押田もと子, 中崎敦夫, 小林進
  • Organizer: 第91回有機合成シンポジウム
  • Place of Presentation: 東京