Synthetic studies on heterocyclic natural products with a potent antitumor activity

• Project/Area Number: 19580130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: TAKAHASHI Shunya The Institute of Physical and Chemical Research, 物質構造解析チーム, 専任研究員 (00202151)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 抗腫瘍活性 / バンレイシアセトゲニン / DNAポリメラーゼ / トポイソメラーゼ / 分子間メタセシス / 腫瘍血管新生 / オバリシン / コンホメーション / フマジリン / 抗腫瘍作用 / 構造活性相関研究

Research Abstract

(1)抗腫瘍活性バンレイシアセトゲニン類の合成研究を行い、構造未定であったモンタナシンD, Eの合成を達成した。また、ピラニシンがDNAポリメラーゼ、トポイソメラーゼ等の酵素の強力な阻害剤になることを見出した。(2)腫瘍血管新生を阻害するテルペノイド(オバリシン、フマジリン)の効率的合成法を検討し、Sharpless不斉酸化反応と分子内メタセシス反応を鍵段階とする短段階合成ルートを開発した。

Research Products

• [Journal Article] Structural revision of thelephantin G by total synthesis and the inhibitory activity against TNF-αproduction (2009)
  • Author(s): Ye Y-Q., Koshino H., Onose J., Negishi C., Yoshikawa K., Abe N., Takahashi S.
  • Journal Title: J. Org. Chem. 74
  • Peer Reviewed
• [Journal Article] Isolation of (E)-9,10-dihydroxy- 2-decenoic acid from royal jelly and determination of the absolute configuration by chemical synthesis (2009)
  • Author(s): Tani H., Takahashi S., Hasumi K., Tatefuji T., Hongo Y., Koshino H.
  • Journal Title: Tetrahedron Asymmetry 20 Pages: 457-460
  • Peer Reviewed
• [Journal Article] Isolation of (E)-9,10-dihydroxy-2-decenoic acid from royal jelly and determination of the absolute configuration by chemical synthesis (2009)
  • Author(s): Tani H.
  • Journal Title: Tetrahedron Asymmetry 20(印刷中)
  • Peer Reviewed
• [Journal Article] Structural determination of montanacin D by total synthesis (2008)
  • Author(s): Takahashi S., Hongo Y., Tsukagoshi Y., Koshino H.
  • Journal Title: Org. Lett. 10 Pages: 4223-4226
  • Peer Reviewed
• [Journal Article] Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase, and human cancer cell growth (2008)
  • Author(s): Takahashi S., Yonezawa Y., Kubota A., Ogawa N., Maeda K., Koshino H., Nakata, T., Yoshida H., and Mizushina Y.
  • Journal Title: Int. J. Oncol. 32 Pages: 451-458
  • Peer Reviewed
• [Journal Article] Structural Determination of Montanacin D by Total Synthesis (2008)
  • Author(s): Takahashi S.
  • Journal Title: Org. Lett. 10 Pages: 4223-4226
  • Peer Reviewed
• [Journal Article] Vialinin A, a novel potent inhibitor of TNF-α production from RBL-2H3 cells (2008)
  • Author(s): Onose, J
  • Journal Title: Biol. Pharm. Bull. 31 Pages: 831-833
  • Peer Reviewed
• [Journal Article] Pyranicin, a nonclassical annonaceous acetogenin, is a protent inhibitoir of DNA polymerase, topoisomerase, and human cancer cell growth (2008)
  • Author(s): Takahashi S.
  • Journal Title: Int. J. Oncol 32 Pages: 451-458
  • Peer Reviewed
• [Journal Article] First total synthesis of vialinin A, a novel and extremely potent inhibitor of TNF-αproduction (2007)
  • Author(s): Ye Y-Q., Koshino H., Onose, J., Yoshikawa K., Abe N., Takahashi S.
  • Journal Title: Org. Lett. 9 Pages: 4131-4134
  • Peer Reviewed
• [Journal Article] First Total Synthesis of Vialinin A, a Novel and Extremely Potent Inhibitor of TNF-α Production (2007)
  • Author(s): Ye Y-Q
  • Journal Title: Org. Lett. 9 Pages: 4131-4134
  • Peer Reviewed
• [Journal Article] Structural Revision of Terpenoids with a (3Z)-2-Methyl-3-penten-2-ol Moiety by Synthesis of (23E)-and (23Z)-Cycloart-23-ene-3β,25-diols (2007)
  • Author(s): Takahashi S.
  • Journal Title: J.Org.Chem. 72 Pages: 4578-4581
  • Peer Reviewed
• [Presentation] Vialinin A関連化合物の合成研究 (2009)
  • Author(s): 叶躍奇,小野瀬淳一,吉川邦衛,阿部尚樹,越野広雪,高橋俊哉
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
• [Presentation] CAST/CNMRシステムの構造訂正への応用(第3報) (2009)
  • Author(s): 越野広雪,高橋俊哉,佐藤寛子
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
• [Presentation] 強力なTNF-α産生阻害活性を有する天然p-テルフェニル類の合成研究 (2008)
  • Author(s): 叶躍奇,小野瀬淳一,吉川邦衛,阿部尚樹,橋爪大輔,越野広雪,高橋俊哉
  • Organizer: 第50回天然有機化合物討論会
  • Place of Presentation: 福岡
• [Presentation] 強力なTNF-α産生阻害剤バイリニンAとその関連化合物の合成 (2008)
  • Author(s): 高橋俊哉
  • Organizer: 第1回理研ケミカルバイオロジー研究領域国際シンポジウム
  • Place of Presentation: 熱海
• [Presentation] 天然起源の抗腫瘍活性物質の化学合成 (2008)
  • Author(s): 高橋俊哉
  • Organizer: 第4回ケミカルバイオロジーシンポジウム-化学?生物融合 領域創製の軌跡-
  • Place of Presentation: 熱海
• [Presentation] 強力なTNF-α産生阻害剤バイリニンAとその関連化合物の合成 (2008)
  • Author(s): 高橋俊哉
  • Organizer: 第1回理研ケミカルバイオロジー研究領域国際シンポジウム
  • Place of Presentation: 静岡県熱海市
• [Presentation] 天然起源の抗腫瘍活性物質の化学合成 (2008)
  • Author(s): 高橋 俊哉
  • Organizer: 第4回ケミカルバイオロジーシンボジウム-化学〜生物融合領域創製の軌跡-
  • Place of Presentation: 静岡県熱海市