Total synthesis of biologically active compounds by using asymmetricorganocatalytic reactions

• Project/Area Number: 23790024
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: ISHIKAWA Hayato 熊本大学, 大学院・自然科学研究科, 准教授 (80453827)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 有機合成化学 / ドミノ反応 / ワンポット合成 / マイクロフロー合成 / 有機触媒 / 不斉反応 / アルカロイド / タミフル / リレンザ / インフルエンザ治療薬

Research Abstract

Efficient total synthesis of Anti-Influenza drug oseltamivir knownas Tamiflu was accomplished. The key process of the synthesis for applied to the industrialscale, is our originally developed asymmetric organocatalytic reactions, domino reaction,one-pot process and micro-flow reactions. In addition, efficient synthetic methods forsynthesis of zanamivir known as Relenza were discovered.

Research Products

• [Journal Article] Diarylprolinol in an Asymmetric AldolReaction of α-Alkyl-α-oxo Aldehydesas an Electrophile (2012)
  • Author(s): Yujiro Hayashi, Yusuke Yasui, MasahiroKojima, Hayato Ishikawa
  • Journal Title: ChemicalCommunication Volume: 48巻 Pages: 4570-4572
  • Peer Reviewed
• [Journal Article] EnantioselectiveIntramolecular [6+2] CycloadditionReaction for the Formation ofTricyclopentanoids and Insight on ItsMechanism from a Computational Study (2011)
  • Author(s): Yujiro Hayashi, Hiroaki Gotoh,Masakazu Honma, Kuppusamy Sankar,Hayato Ishikawa, Kohzo Konno, HiroharuYui, Seiji Tsuzuki, Tadafumi Uchimaru,Organocatalytic
  • Journal Title: Journal of American Chemical Society Volume: 133巻 Pages: 20175-20185
  • Peer Reviewed
• [Journal Article] SpontaneousConversion of 3-Alkyl-substituted3-Hydroxyperoxypyrrolidine-2 (2011)
  • Author(s): Md. Aminul Haque, Hayato Ishikawa,Hiroshi Nishino
  • Journal Title: 4-diones into5-Alkyl-5hydroxyoxazolidin-4-ones,Chemistry Letters Volume: 40巻 Pages: 1349-1351
  • Peer Reviewed
• [Journal Article] Synthesis of(-)-Oseltamivir by Using aMicroreactor in the CurtiusRearrangement (2011)
  • Author(s): Hayato Ishikawa, Bojan P. Bondzic,Yujiro Hayashi
  • Journal Title: European Journal ofOrganic Chemistry Volume: 6020-6031 Pages: 6020-6031
  • Peer Reviewed
• [Journal Article] One-pot Synthesis of ChiralAziridines by a Domino Reaction usingDesulfonylative Formation on theN-Tosyl Imine of Chloroacetaldehydewith an Asymmetric Mannich Reaction asa Key Step (2011)
  • Author(s): Yujiro Hayashi, Tatsuya Urushima,Daisuke Sakamoto, Kou Torii, HayatoIshikawa
  • Journal Title: Chemistry a EuropeanJournal Volume: 17巻 Pages: 11715-11718
  • Peer Reviewed
• [Journal Article] Asymmetric MannichReaction of Imines Derived fromAliphatic and Aromatic AldehydesCatalyzed by Diarylprolinol SilylEther (2011)
  • Author(s): Tatsuya Urushima, Hayato Ishikawa,Yujiro Hayashi
  • Volume: 17巻
  • Pages: 8273-8276
  • Peer Reviewed
• [Journal Article] Benohoud, Hayato Ishikawa, DieterSeebach, Yujiro Hayashi (2011)
  • Author(s): Krystyna Patora-Komisarska, Meryem Benohoud, Hayato Ishikawa, DieterSeebach, Yujiro Hayashi
  • Journal Title: Helvetica Chemica Acta Volume: 94巻 Pages: 719-745
  • Peer Reviewed
• [Journal Article] Oxidative andEnantioselective Cross-Coupling ofAldehydes and Nitromethane Catalyzedby Diphenylprolinol Silyl Ether (2011)
  • Author(s): Yujiro Hayashi, Takahiko Itoh, HayatoIshikawa
  • Journal Title: Angewandte Chemie InternationalEdition Volume: 50巻 Pages: 3920-3924
  • Peer Reviewed
• [Journal Article] Synthesis of (-)-Oseltamivir using a microreactor in the Curtius rearrangement (2011)
  • Author(s): H. Ishikawa
  • Journal Title: Eur. J. Org. Chem. Volume: 2011 Issue: 30 Pages: 6020-6031
  • DOI: 10.1002/ejoc.201100074
  • Peer Reviewed
• [Journal Article] Asymmetric One-Pot Four-Component Coupling Reaction: Synthesis of Substituted Tetrahydropyrans Catalyzed by Diphenylprolinol Silyl Ether (2011)
  • Author(s): H. Ishikawa
  • Journal Title: Angew. Chem. Int. Ed. Volume: 50 Issue: 16 Pages: 3774-3779
  • DOI: 10.1002/anie.201005386
  • Peer Reviewed
• [Journal Article] Organocatalyzed Michael Addition of Aldehydes (2011)
  • Author(s): D. Seebach, Y. Hayashi et al.
  • Journal Title: Helvetica Chimica Acta Volume: 94 Issue: 5 Pages: 719-745
  • DOI: 10.1002/hlca.201100122
  • Peer Reviewed
• [Presentation] モノテルペノイドインドールアルカロイド生合成重要中間体ガイソチザールの全合成研究 (2012)
  • Author(s): 牛島大佑、中島梨絵、石川勇人
  • Organizer: 第5回有機触媒シンポジウム
  • Place of Presentation: 学習院大学
  • Year and Date: 2012-10-26
• [Presentation] 不斉有機触媒反応を鍵工程とする生物活性アルカロイドの効率的全合成研究 (2012)
  • Author(s): 石川勇人
  • Organizer: 新学術領域「有機分子触媒による未来型分子変換」第1回全体会議
  • Place of Presentation: 京都大学
  • Year and Date: 2012-06-09
• [Presentation] モノテルペノイドインドールアルカロイド生合成重要中間体ガイソチザールの全合成研究 (2012)
  • Author(s): 牛島大佑、中島梨絵、石川勇人
  • Organizer: 第5回 有機触媒シンポジウム
  • Place of Presentation: 学習院大学
• [Presentation] 不斉有機触媒反応を鍵工程とした生物活性化合物の効率的全合成 (2011)
  • Author(s): 石川勇人
  • Organizer: 機合成化学協会・九州山口支部:有機合成化学講演会
  • Place of Presentation: 九州大学百周年記念館
  • Year and Date: 2011-05-20
• [Presentation] 不斉有機触媒反応を鍵工程とした生物活性化合物の効率的全合成 (2011)
  • Author(s): 石川勇人
  • Organizer: 有機合成化学協会・九州山口支部：有機合成化学講演会(招待講演)
  • Place of Presentation: 九州大学
• [Book] Asymmetric Synthesis IIMore Methods and Application,Edited by Mathias Cristmann (2012)
  • Author(s): Ishikawa Hayato, Yujiro Hayashi,Wiley-VCH
  • Publisher: StefanBrase
• [Remarks]
  • URL: http://www.sci.kumamoto-u.ac.jp/~ishikawa/ishikawa-lab/Top.html
• [Remarks] 石川研究室ホームページ
  • URL: http://www.sci.kumamoto-u.ac.jp/~ishikawa/ishikawa-lab/Top.html