Total Synthesis and Mechanistic Studies on Cortistatins,Anti-angiogenesis Reagents

• Project/Area Number: 19710175
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: Tohoku University
• Principal Investigator: YAMASHITA Shuji Tohoku University, 大学院・理学研究科, 助教 (50419991)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,740,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥540,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 天然物有機化学 / 全合成 / コルチスタチン / 血管新生阻害 / 抗腫瘍活性 / 収束的全合成 / イソキノリン / 求核付加反応 / ラジカル還元 / 連続四置換炭素 / 収束的合成 / 電子環状反応 / ラジカル反応 / Knoevenagel反応

Research Abstract

Cortistatins exhibit extremely strong cytotoxicity against human umbilical vein endothelial cells. Owing to its unique inhibition activity of angiogenesis and unusual steroidal structure, cortistatins have currently become the most challenging targets in the total synthesis. We originally developed the concise and highly stereoselective routes to cortistatin A and J, the most potent congeners.

Research Products

• [Journal Article] Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A (2009)
  • Author(s): S. Yamashita, K. Kitajima, K. Iso, M. Hirama
  • Journal Title: Tetrahedron Lett 50 Pages: 3277-3279
  • Peer Reviewed
• [Journal Article] Efficient and stereoselective installation of isoquinoline : formal total synthesis of cortistatin A (2009)
  • Author(s): S.Yamashita, K.Kitajima, K.Iso, M.Hirama
  • Journal Title: Tetrahedron Letters 50 Pages: 3277-3279
  • Peer Reviewed
• [Journal Article] Efficient and stereoselective installation of isoquinoline : formal total synthesis of cortistatin A (2009)
  • Author(s): S. Yamashita, K. Kitajima, K. Iso. M. Hirama
  • Journal Title: Tetrahedron Letters 50 (In press)
  • Peer Reviewed
• [Journal Article] A Concise Synthesis of the Pentacyclic Framework of Cortistatins (2008)
  • Author(s): S. Yamashita, K. Iso, M. Hirama
  • Journal Title: Org. Lett 10 Pages: 3413-3415
  • Peer Reviewed
• [Journal Article] A Concise Synthesis of the Pentacyclic Framework of Cortistatins (2008)
  • Author(s): S. Yamashita, K. Iso, M. Hirama
  • Journal Title: Organic Letters 10 Pages: 3413-3415
  • Peer Reviewed
• [Presentation] コルチスタチンAおよびJの全合成 (2010)
  • Author(s): 磯健太郎・北嶌一樹・山下修治・平間正博
  • Organizer: 日本化学会第90回春季年会
  • Place of Presentation: 大阪・大阪
  • Year and Date: 2010-03-29
• [Presentation] コルチスタチンAおよびJの全合成 (2010)
  • Author(s): 磯健太郎・北嶌一樹・山下修治・平間正博
  • Organizer: 日本化学会第90回春季年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-28
• [Presentation] コルチスタチンAおよびJの全合成 (2009)
  • Author(s): 磯健太郎・北嶌一樹・山下修治・平間正博
  • Organizer: 第51回天然有機化合物討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-10-07
• [Presentation] コルチスタチンAおよびJの全合成 (2009)
  • Author(s): 磯健太郎・北嶌一樹・山下修治・平間正博
  • Organizer: 第51回天然有機化合物討論会
  • Place of Presentation: 愛知・名古屋
  • Year and Date: 2009-10-07
• [Presentation] コルチスタチンAの全合成研究(1) (2009)
  • Author(s): 北嶌一樹・磯健太郎・山下修治・平間正博
  • Organizer: 日本化学会第89回春季年会
  • Place of Presentation: 千葉ほか
  • Year and Date: 2009-03-28
• [Presentation] コルチスタチン類の全合成研究(1) (2009)
  • Author(s): 北罵一樹・磯健太郎・山下修治・平間正博
  • Organizer: 日本化学会第89回春季年会
  • Place of Presentation: 千葉・船橋
  • Year and Date: 2009-03-28
• [Presentation] コルチスタチン類の全合成研究(2) (2009)
  • Author(s): 磯健太郎・北嶌一樹・山下修治・平間正博
  • Organizer: 日本化学会第89回春季年会
  • Place of Presentation: 千葉・船橋
  • Year and Date: 2009-03-28
• [Presentation] コルチスタチン類の全合成研究 (2008)
  • Author(s): 磯 健太郎・北嶌一樹・山下修治・平間正博
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京・渋谷
  • Year and Date: 2008-03-27
• [Presentation] コルチスタチン類の全合成研究(2) (2008)
  • Author(s): 北嶌一樹・磯 健太郎・山下修治・平間正博
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京・渋谷
  • Year and Date: 2008-03-27
• [Presentation] コルチスタチン類の全合成研究 (2007)
  • Author(s): 北嶌一樹・磯 健太郎・山下修治・平間正博
  • Organizer: 日本化学会東北大会
  • Place of Presentation: 山形・山形
  • Year and Date: 2007-09-21