Total Synthesis of Biologically Active Compounds PossessingCyclohexylamine Skeleton.

• Project/Area Number: 20750036
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Organic chemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: ISHIKAWA Hayato Tokyo University of Science, 工学部, 助教 (80453827)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 有機合成化学 / 有機触媒 / ワンポット反応 / オセルタミビル / ABT-341 / ドミノ反応 / マイクロフローシステム / カラムフリー合成 / カナマイシンA / パンクラチスタチン

Research Abstract

Efficient total synthesis of Anti-Influenza drug Oseltamivir and diabetes drug ABT-341 were accomplished. The key process of the synthesis for applied to the industrial scale, is our originally developed asymmetric organocatalytic reactions, domino reaction and one-pot process.

Research Products

• [Journal Article] Asymmetric One-Pot Four-Component Coupling Reaction : Synthesis of Substituted Tetrahydropyrans Catalyzed by DiphenylprolinolSilyl Ether. (2011)
  • Author(s): Hayato Ishikawa, Satoshi Sawano, Yusuke Yasui, Yusuke Shibata, Yujiro Hayashi.
  • Journal Title: Angewandte Chemie International Edition.(インターネット上で公開) 50巻(印刷中)
  • Peer Reviewed
• [Journal Article] One-Pot High-Yielding Synthesis of the DPP4-Selective Inhibitor ABT-341 by a Four-Component Coupling Mediated by a Diphenylprolinol Silyl Ether. (2011)
  • Author(s): Hayato Ishikawa, Masakazu Honma, Yujiro Hayashi.
  • Journal Title: Angewandte Chemie International Edition 50巻 Pages: 2824-2827
  • Peer Reviewed
• [Journal Article] Asymmetric One-Pot Four-Component Coupling Reaction : Synthesis of Substituted Tetrahydropyrans Catalyzed by Diphenylprolinol Silyl Ether (2011)
  • Author(s): Hayato Ishikawa, Satoshi Sawano, Yusuke Yasui, Yusuke Shibata, Yujiro Hayashi
  • Journal Title: Angewandte Chemie International Edition Volume: 50
  • Peer Reviewed
• [Journal Article] One-Pot High-Yielding Synthesis of the DPP4-Selective Inhibitor ABT-341 by a Four-Component Coupling Mediated by a Diphenylprolinol Silyl Ether (2011)
  • Author(s): Hayato Ishikawa, Masakazu Honma, Yujiro Hayashi
  • Journal Title: Angewandte Chemie International Edition Volume: 50 Pages: 2824-2827
  • Peer Reviewed
• [Journal Article] 有機触媒を用いた(-)-オセルタミビルの3ポット合成 (2010)
  • Author(s): 石川勇人、林雄二郎
  • Journal Title: ファインケミカル 39巻 Pages: 5-12
  • Peer Reviewed
• [Journal Article] High-Yielding Synthesis of the Anti-Influenza Neuraminidase Inhibitor (-)-Oseltamivir by Two "One-Pot" Sequences (2010)
  • Author(s): Hayato Ishikawa, Takaki Suzuki, Hideo Orita, Tadafumi Uchimaru, Yujiro Hayashi.
  • Journal Title: Chemistry-A European Journal 16巻 Pages: 12616-12626
  • Peer Reviewed
• [Journal Article] 有機触媒を用いた(-)□オセルタミビルの3ポット合成 (2010)
  • Author(s): 石川勇人、林雄二郎
  • Journal Title: ファインケミカル Volume: 39 Pages: 5-12
  • Peer Reviewed
• [Journal Article] High-Yielding Synthesis of the Anti-Influenza Neuraminidase Inhibitor(-)-Oseltamivir by Two "One-Pot" Sequences (2010)
  • Author(s): Hayato Ishikawa, Takaki Suzuki, Hideo Orita, Tadafumi Uchimaru, Yujiro Hayashi
  • Journal Title: Chemistry-A European Journal Volume: 16 Pages: 12616-12626
  • Peer Reviewed
• [Journal Article] High-Yielding Synthesis of the Anti-Influenza Neuramidase Inhibitor (-)-Oseltamivir by Three "One-Pot" Operations. (2009)
  • Author(s): Hayato Ishikawa, Takaki Suzuki, Yujiro Hayashi.
  • Journal Title: Angewandte Chemie International Edition 48巻 Pages: 4904-4916
  • Peer Reviewed
• [Journal Article] Asymmetric Aldol Reaction of Acetaldehyde and Isatin Derivatives for the Total Syntheses of ent-Convolutamydine E and CPC-1 and a Half Fragment of Madindoline A and B. (2009)
  • Author(s): Takahiko Itoh, Hayato Ishikawa, Yujiro Hayashi.
  • Journal Title: Organic Letters 11巻 Pages: 3854-3857
  • Peer Reviewed
• [Journal Article] Diphenylprolinol Silyl Ether as a Catalyst in an Asymmetric, Catalytic, and Direct Michael Reaction of Nitroethanol with α,β-Unsaturated Aldehydes. (2009)
  • Author(s): Hiroaki Gotoh, Daichi Okamura, Hayato Ishikawa, Yujiro Hayashi.
  • Journal Title: Organic Letters 11巻 Pages: 4056-4059
  • Peer Reviewed
• [Journal Article] Total Synthesis and Determination of the Absolute Configuration of FD-838, a Naturally Occurring Azaspirobicyclic Product. (2009)
  • Author(s): Yujiro Hayashi, Kuppsamy Sankar, Hayato Ishikawa, Yuriko Nozawa, Kazutoshi Mizoue, Hideaki Kakeya.
  • Journal Title: Bioorganic & Medicinal Chemistry Letters. 19巻 Pages: 3863-3865
  • Peer Reviewed
• [Journal Article] Diphenylprolinol Silyl Ether Catalysis in an Asymmetric Formal Carbo [3+3] Cycloaddition Reaction via a Domino Michael/Knoevenagel Condensation. (2009)
  • Author(s): Yujiro Hayashi, Maya Toyoshima, Hiroaki Gotoh, Hayato Ishikawa.
  • Journal Title: Organic Letters 11巻 Pages: 45-48
  • Peer Reviewed
• [Journal Article] High-Yielding Synthesis of the Anti-Influenza Neuramidase Inhibitor(-)-Oseltamivir by Three "One-Pot" Operations (2009)
  • Author(s): Hayato Ishikawa, Takaki Suzuki, Yujiro Hayashi
  • Journal Title: Angewandte Chemie International Edition 48 Pages: 4904-4916
  • Peer Reviewed
• [Journal Article] Asymmetric Aldol Reaction of Acetaldehyde and Isatin Derivatives for the Total Syntheses of ent-Convolutamydine E and CPC-1 and a Half Fragment of Madindoline A and B (2009)
  • Author(s): Takahiko Itoh, Hayato Ishikawa, Yujiro Hayashi
  • Journal Title: Organic Letters 11 Pages: 3854-3857
  • Peer Reviewed
• [Journal Article] Diphenylprolinol Silyl Ether as a Catalyst in an Asymmetric, Catalytic, and Direct Michael Reaction of Nitroethanol with α,β-unsaturated Aldehydes (2009)
  • Author(s): Hiroaki Gotoh, Daichi Okamura, Hayato Ishikawa, Yujiro Hayashi
  • Journal Title: Organic Letters 11 Pages: 4056-4059
  • Peer Reviewed
• [Journal Article] Total Synthesis and Determination of the Absolute Configuration of FD-838, a Naturally Occurring Azaspirobicyclic product (2009)
  • Author(s): Yujiro Hayashi, Kuppsamy Sankar, Hayato Ishikawa, Yuriko Nozawa, Kazutoshi Mizoue, Hideaki Kakeya
  • Journal Title: Bioorganic & Medicinal Chemistry Letters 19 Pages: 3863-3865
  • Peer Reviewed
• [Journal Article] Diphenylprolinol Silyl Ether Catalysis in an Asymmetric Formal Carbo [3+3] Cycloaddition Reaction via a Domino Michael/Knoevenagel Condensation (2009)
  • Author(s): Yujiro Hayashi, Maya Toyoshima, Hiroaki Gotoh, Hayato Ishikawa
  • Journal Title: Organic Letters 11 Pages: 45-48
  • Peer Reviewed
• [Journal Article] Direct Organocatalytic Mannich Reaction of Acetaldehyde : An Improved Catalyst and Mechanistic Insight from a Computational Study. (2008)
  • Author(s): Yujiro Hayashi, Tsubasa Okano, Takahiko Itoh, Tatsuya Urushima, Hayato Ishikawa, Tadafumi Uchimaru.
  • Journal Title: Angewandte Chemie International Edition. 47巻 Pages: 6657-6660
  • Peer Reviewed
• [Journal Article] Reaction of Acetaldehyde Catalyzed by Diarylprolinol. (2008)
  • Author(s): Yujiro Hayashi, Sampak Samanta, Takahiko Itoh, Hayato Ishikawa, Asymmetric, Catalytic, Direct Self-Aldol
  • Journal Title: Organic Letters 10巻 Pages: 5581-5583
  • Peer Reviewed
• [Journal Article] Direct Organocatalytic Mannich Reaction of Acetaldehyde : An Improved Catalyst and Mechanistic Insight from a Computational Study (2008)
  • Author(s): Yujiro Hayashi, Tsubasa Okano, Takahiko Itoh, Tatsuya Urushima, Hayato Ishikawa, Tadafumi Uchimaru
  • Journal Title: Angewandte Chemie International Edition 47 Pages: 6657-6660
  • Peer Reviewed
• [Journal Article] Asymmetric, Catalytic ,and Direct Self-Aldol Reaction of Acetaldehyde Catalyzed by Diarylprolinol (2008)
  • Author(s): Yujiro Hayashi, Sampak Samanta, Takahiko Itoh, Hayato Ishikawa
  • Journal Title: Organic Letters 10 Pages: 5581-5583
  • Peer Reviewed
• [Presentation] (-)-オセルタミビルの2ポット、カラムフリー合成への改良 (2010)
  • Organizer: 第52回天然有機化合物討論会
  • Place of Presentation: グランシップ静岡
  • Year and Date: 2010-09-30
• [Presentation] (-)-オセルタミビルの3ポット合成 (2010)
  • Organizer: 日本薬学会130年会一般シンポジウムS31「薬学における有機化学の原点回帰とこれから」
  • Place of Presentation: 岡山大学
  • Year and Date: 2010-03-28
• [Presentation] ビンドリン、ビンブラスチン、オセルタミビルの効率的全合成 (2009)
  • Organizer: 2009東日本スクリプス会
  • Place of Presentation: ゆうぽうと五反田
  • Year and Date: 2009-11-07
• [Presentation] 不斉有機触媒反応を鍵反応とした生物活性化合物の全合成 (2009)
  • Organizer: 第4回プロセス化学ラウンジ
  • Place of Presentation: TKP熱海研修センター
  • Year and Date: 2009-11-05
• [Presentation] 不斉有機触媒反応を鍵反応とする生物活性化合物の全合成 (2009)
  • Organizer: 日本化学会第89春期年会第23回若い世代の特別講演
  • Place of Presentation: 日本大学
  • Year and Date: 2009-03-28
• [Remarks] ホームページ等
  • URL: http://www.ci.kagu.tus.ac.jp/lab/org-chem1/member/Hayato%20Ishikawa.html
• [Remarks]
  • URL: http://www.ci.kagu.tus.ac.jp/lab/org-chem1/member/Hayato%20Ishikawa.html
• [Remarks]
  • URL: http://www.ci.kagu.tus.ac.jp/lab/org-cheml/member/Hayato%20Ishikawa.html
• [Patent(Industrial Property Rights)] リン酸オセルタミビルの中間体化合物 (2008)
  • Inventor(s): 林雄二郎、石川勇人
  • Industrial Property Rights Holder: 林雄二郎、石川勇人
  • Filing Date: 2008-05-30
• [Patent(Industrial Property Rights)] リン酸オセルタミビルの中間体化合物 (2008)
  • Inventor(s): 林雄二郎、石川勇人
  • Industrial Property Rights Holder: 林雄二郎、石川勇人
  • Industrial Property Number: 2008-143226
  • Filing Date: 2008-05-30