Intramolecula SN2' Cyclization Reaction by 1, 3-Chirality Transfer and Total Synthesis of Heterocyclic Natural Products

• Project/Area Number: 21590030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: UENISHI Jun' ichi 京都薬科大学, 薬化学分野, 教授 (50167285)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 1, 3-不斉転写 / 分子内SN2'型環化 / 天然化合物 / アルカロイド / マクロライド / 全合成 / Pd-catalyst / 選択的反応 / 1.3-不斉転写 / 分子内SN2'型環化反応 / 1,3-不斉転写

Research Abstract

New synthetic organic reaction has been developed and it has utilized for the synthesis of some natural products. Thus, optically active tetrrahydropyran, tetrahydrofuran, and piperidine rings have been prepared selectively by Pd(II)-catalyzed reaction. The reaction mechanism was proposed and proven on the basis of experimental evidence. For the synthesis of tetrahydroisoquinoline, Bi(OTf)_3 was found to be effective as a Lewis acid catalyst. Anti-cancer natural product(-)-apicularen A as well as natural alkaloid(-)-trolline and others have been synthesized.

Research Products

• [Journal Article] Total Synthesis and Biological Evaluation of(-)-Apicularen A and Its Analogues (2012)
  • Author(s): Sanjay S. Palimkar, Jun' ichi Uenishi, Hiromi, Ii
  • Journal Title: J. Org. Chem Volume: 77巻 Pages: 388-299
  • Peer Reviewed
• [Journal Article] Total Synthesis and Biological Evaluation of (-)-Apicularen A and its Analogues (2012)
  • Author(s): Sanjay S.Palimkar, Jun'ichi Uenishi, Hitomi Ii
  • Journal Title: J.Org.Chem. Volume: 77 Issue: 1 Pages: 388-399
  • DOI: 10.1021/jo2019762
  • Peer Reviewed
• [Journal Article] Stereoselective Synthesis of Tetrahydroisoquinoline Alkaloids :(-)-Trolline,(+)-Crispin A, (+)-Oleracein E (2011)
  • Author(s): Nobuyuki Kawai, Yuka Matsuda, Jun' ichi Uenishi
  • Journal Title: Tetrahedron Volume: 67巻 Pages: 8648-8653
  • Peer Reviewed
• [Journal Article] Pd^<II>-catalyzed Cascade Reaction with 1, 3-Chirality Transfer ; Stereoselective Synthesis of Chiral Non-racemic 2, 2'-THF-THF Ring Units (2011)
  • Author(s): Jun' ichi Uenishi, Yuhei Fujikura, Nobuyuki Kawai
  • Journal Title: Org. Lett Volume: 13巻 Pages: 2350-2353
  • Peer Reviewed
• [Journal Article] Synhesis of Chiral 1-Substituted Tetrahydroisoquinolines by the Intramolecular 1, 3-Chirality Transfer Reaction Catalyzed by Bi(OTf)_3 (2011)
  • Author(s): Nobuyuki Kawai, Ryuzo Abe, Yuka Matsuda, Jun' ichi Uenishi
  • Journal Title: J. Org. Chem Volume: 76巻 Pages: 2002-2114
  • Peer Reviewed
• [Journal Article] Stereoselective synthesis of tetrahydroisoquinoline alkaloids : (-)-trolline, (+)-crispin A, (+)-oleracein E (2011)
  • Author(s): Nobuyuki Kawai, Mika Matsuda, Jun'ichi Uenishi
  • Journal Title: Tetrahedron Volume: 67 Pages: 8648-8653
  • Peer Reviewed
• [Journal Article] Pd^<II>-catalyzed cascade reaction with 1,3-chirality transfer ; stereoselective synthesis of chiral nonracemic 2,2'-THF-THF ring units (2011)
  • Author(s): Jun'ichi Uenishi, Yuhei Fujikura, Nobuyuki Kawai
  • Journal Title: Org.Lett. Volume: 13 Issue: 9 Pages: 2350-2353
  • DOI: 10.1021/ol2005984
  • Peer Reviewed
• [Journal Article] Synthesis of Chiral 1-Substituted Tetrahydroisoquinolines by the Intramolecular 1, 3-Chirality Transfer Reaction Catalyzed by Bi(OTf)_3 (2011)
  • Author(s): N.Kawai, R.Abe, M.Matsuda, J.Uenishi
  • Journal Title: J.Org.Chem. Volume: 76 Pages: 2002-2014
  • Peer Reviewed
• [Journal Article] Total Synthesis of(-)-apicularen A (2010)
  • Author(s): Sanjay S. Palimkar, Jun' ichi Uenishi
  • Journal Title: Org. Lett Volume: 12巻 Pages: 4160-4163
  • NAID: 110009757759
  • Peer Reviewed
• [Journal Article] A Short Access to Chiral Non-racemic Oxa-and Azaheterocycles by Cross-metathesis and Pd-Catalyzed Cyclization Sequence (2010)
  • Author(s): Jun' ichi Uenishi, Yogesh S. Vikhe
  • Journal Title: Hetrocycles Volume: 80巻 Pages: 1463-1469
  • Peer Reviewed
• [Journal Article] Total Synthesis of (-)-Apicularen A (2010)
  • Author(s): Sanjay S.Palimkar, Jun'ichi Uenishi
  • Journal Title: Organic Letters Volume: 12 Pages: 4160-4163
  • NAID: 110009757759
  • Peer Reviewed
• [Journal Article] A Short Access to Chiral Non-racemic Oxa- and Azaheterocycles by Cross-metathesis and Pd-Catalyzed Cyclization Sequence (2010)
  • Author(s): J.Uenishi, Y.S.Vikhe
  • Journal Title: Hetrocycles Volume: 80 Pages: 1463-1469
  • Peer Reviewed
• [Journal Article] A Short Access to Chiral Non-racemic Oxa- and Azaheterocycles by Cross-metathesis and Pd-Catalyzed Cyclization Sequence (2010)
  • Author(s): J.Uenishi, Y.S.Vikhe
  • Journal Title: Hetrocycles 80 Pages: 1463-1469
  • Peer Reviewed
• [Journal Article] Lewis Acid Catalyzed Intramolecular Amino Substitution via 1, 3-Chirality Transfer (2009)
  • Author(s): Nobuyuki Kawai, Ryuzo Abe, Jun' ichi Uenishi
  • Journal Title: Tetrahedron Lett Volume: 50巻 Pages: 6580-6583
  • Peer Reviewed
• [Journal Article] Stereochemistry of Intermolecular Oxypalladation : Pd^<II>-Catalyzed 1, 3-Chirality Transfer Reaction of Chiral Allylic Alcohol with Methanol (2009)
  • Author(s): Yogesh. S. Vikhe, Sudhir M. Hande, Nobuyuki Kawai, Jun' ichi Uenishi
  • Journal Title: J. Org. Chem Volume: 74巻 Pages: 5174-5180
  • Peer Reviewed
• [Journal Article] Total Synthesis of Aspergillide B and Structural Discrepancy of Aspergillide A (2009)
  • Author(s): Sudhir M. Hande, Jun' ichi Uenishi
  • Journal Title: Tetrahedron Lett Volume: 50巻 Pages: 189-192
  • Peer Reviewed
• [Journal Article] An Efficient Synthesis of 2- and 2, 6-Substituted Piperidines using Pd^<II>-Catalyzed1, 3-Chirality Transfer Reaction (2009)
  • Author(s): Sudhir M. Hande, Nobuyuki Kawai, Jun' ichi Uenishi
  • Journal Title: J. Org. Chem Volume: 74巻 Pages: 244-253
  • Peer Reviewed
• [Journal Article] Lewis Acid Catalyzed Intramolecular Amino Substitution via 1, 3-Chirality Transfer (2009)
  • Author(s): N.Kawai, R.Abe, J.Uenishi
  • Journal Title: Tetrahedron Lett. 50 Pages: 6580-6583
  • Peer Reviewed
• [Journal Article] Stereochemistry of Intermolecular Oxypalladation : Pd^<II>-Catalyzed 1, 3-Chirality Transfer Reaction of Chiral Allylic Alcohol with Methanol (2009)
  • Author(s): Y.S.Vikhe, S.M.Hande, N.Kawai, J.Uenishi
  • Journal Title: J.Org.Chem. 74 Pages: 5174-5180
  • Peer Reviewed
• [Presentation] Neutral organocatalysts promotin g dehydrative cyclization with 1, 3-chiralty transfer (2012)
  • Author(s): Nobuyuki Kawai, Koichi Ishibashi, Jun'ichi Uenishi
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium
  • Place of Presentation: 東京京王プラザ
  • Year and Date: 2012-11-30
• [Presentation] スルホン酸エステルを触媒とする1, 3-不斉転写反応とテトラヒドロイソキノリンアルカイドの合成 (2012)
  • Author(s): 河井伸之、石橋洸一、松田望花、Jannapur eddy Raju、上西潤一
  • Organizer: 第37回反応と合成の進歩シンポジウム
  • Place of Presentation: 徳島阿波銀ホール
  • Year and Date: 2012-11-08
• [Presentation] Neutral organocatalysts promoting dehydrative cyclization with 1,3-chiralty transfer (2011)
  • Author(s): Nobuyuki Kawai, Koichi Ishibashi, Jun'ichi Uenishi
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium
  • Place of Presentation: 東京
  • Year and Date: 2011-11-30
• [Presentation] スルホン酸エステルを触媒とする1,3-不斉転写反応とテトラヒドロイソキノリンアルカイドの合成 (2011)
  • Author(s): 河井伸之、石橋洸一、松田望花、Jannapureddy Raju、上西潤一
  • Organizer: 第37回反応と合成の進歩シンポジウム
  • Place of Presentation: 徳島
  • Year and Date: 2011-11-08
• [Presentation] 1, 3-不斉転写の化学とこれを用いる天然物合成 (2011)
  • Author(s): 上西潤一
  • Organizer: 第38回有機反応懇談会
  • Place of Presentation: 大阪府立大学
  • Year and Date: 2011-08-03
• [Presentation] 1,3-不斉転写の化学とこれを用いる天然物合成 (2011)
  • Author(s): 上西潤一
  • Organizer: 第38回有機反応懇談会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-03
• [Presentation] (-)-Apicularen Aの全合成 (2010)
  • Author(s): Sanjay S. Palimkar, Jun'ichi Uenishi
  • Organizer: 第52回天然有機化合物討論会
  • Place of Presentation: 静岡県コンベンションアーツセンター
  • Year and Date: 2010-10-01
• [Presentation] Total synthesis of(-)-apicularen A (2010)
  • Author(s): Sanjay S. Palimkar, Jun'ichi Uenishi
  • Organizer: The 21st French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: 京都ガーデンパレス
  • Year and Date: 2010-05-11
• [Presentation] Total synthesis of (-)-apicularen A (2010)
  • Author(s): Sanjay S.Palimkar, Jun'ichi Uenishi
  • Organizer: The 21st French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: 京都ガーデンパレス
  • Year and Date: 2010-05-11
• [Presentation] ルイス酸触媒によるキラルな2級アリルアルコールへの窒素求核剤の分子内SN2'反応 (2009)
  • Author(s): 河井伸之、阿部隆三、松田望花、Sudhir Mahadeo Hande、上西潤一
  • Organizer: 35回反応と合成の進歩シンポジウム大会
  • Place of Presentation: 金沢文化ホール
  • Year and Date: 2009-11-16
• [Presentation] ルイス酸触媒によるキラルな2級アリルアルコールへの窒素求核剤の分子内SN2'反応 (2009)
  • Author(s): 河井伸之、阿部隆三、松田望花、Sudhir Mahadeo Hande、上西潤一
  • Organizer: 35回反応と合成の進歩シンポジウム大会
  • Place of Presentation: 金沢
  • Year and Date: 2009-11-16
• [Book] 有機化学演習 (2010)
  • Author(s): 上西潤一、和田昭盛
  • Publisher: 京都廣川書店
• [Remarks]
  • URL: http://www.kyoto-phu.ac.jp/labo/yakka/
• [Patent(Industrial Property Rights)] 光学活性な1位置換テトラヒドロイソキノリン化合物の製造方法 (2011)
  • Inventor(s): 上西潤一、河井伸之
  • Industrial Property Rights Holder: 上西潤一、河井伸之
  • Industrial Property Number: 2011-040667
  • Filing Date: 2011-02-25