Asymmetric Total Synthesis of Indole Alkaloids via 1,3-DipolarCycloaddition of a Carbonyl Ylide

• Project/Area Number: 22790001
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: University of Toyama (2011); Hokkaido University (2010)
• Principal Investigator: NAMBU Hisanori 富山大学, 大学院・医学薬学研究部(薬学), 准教授 (80399956)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: インドールアルカロイド / 不斉合成 / 付加環化反応 / カルボニルイリド / インドール / ロジウム(II)錯体 / 触媒反応 / タンデム反応

Research Abstract

（1) Asymmetric intramolecular cycloaddition of carbonyl ylides derived from indolyl-substituted α-diazo-β-ketoesters under the influence of Rh2（S-TCPTTL)4 provided cycloadducts in up to 90% ee and with perfect endo diastereoselectivity.（2) Asymmetric intermolecular cycloaddition of carbonyl ylides derived from trichloroethyl esterpossessingα-diazo-β-ketoesters with N-methylindole using Rh2（S-TCPTTL)4 gave a 96:4 mixture of exo- and endo-cycloadducts in 96% yield with 97% ee for exo adduct.

Research Products

• [Journal Article] Catalytic Enantioselective Intermolecular Cycloaddition of Diazodiketoester-Derived Carbonyl Ylides with Indoles Using Chiral Dirhodium(II) Carboxylates (2011)
  • Author(s): Shimada, N.; Oohara, T.; Krishnamurthi, J.; Nambu, H.; Hashimoto, S.
  • Journal Title: Org. Lett. Volume: 13 Issue: 23 Pages: 6284-6287
  • DOI: 10.1021/ol2027625
  • Peer Reviewed
• [Journal Article] Continuous Flow System with a Polymer-Supported Dirhodium(II) Catalyst: Application to EnantioselectiveCarbonyl Ylide Cycloaddition Reactions (2011)
  • Author(s): Takeda, K.; Oohara, T.; Shimada, N.; Nambu, H.; Hashimoto, S.
  • Journal Title: Chem. Eur. J. Volume: 17 Pages: 13992-13998
  • Peer Reviewed
• [Journal Article] Catalytic Enantioselective C–H Functionalization of Indoles with α-Diazopropionates Using Chiral Dirhodium(II) Carboxylates: Asymmetric Synthesis of the (+)-α-Methyl-3-indolylacetic Acid Fragment of Acremoauxin A (2011)
  • Author(s): Goto, T.; Natori, Y.; Takeda, K.; Nambu, H.; Hashimoto, S.
  • Journal Title: Tetrahedron: Asymmetry. Volume: 22 Issue: 8 Pages: 907-915
  • DOI: 10.1016/j.tetasy.2011.05.011
  • NAID: 120003260036
  • Peer Reviewed
• [Journal Article] Continuous Flow System with a Polymer-Supported Dirhodium(II) Catalyst: Application to Enantioselective Carbonyl Ylide Cycloaddition Reactions (2011)
  • Author(s): Takeda, K.; Oohara, T.; Shimada, N.; Nambu, H.; Hashimoto, S.
  • Journal Title: Chem. Eur. J. Volume: 17 Issue: 50 Pages: 13992-13998
  • DOI: 10.1002/chem.201102733
  • Peer Reviewed
• [Journal Article] Highly Enantioselective Cyclopropenation Reaction of 1-Alkynes with α-Alkyl-α-diazoesters Catalyzed by Dirhodium(II) Carboxylates (2011)
  • Author(s): Goto,T.; Takeda,K.；Shimada,N.;Nambu,H.; Anada,M;Shiro.M; Ando,.K; Hashimoto,S.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 50 Issue: 30 Pages: 6803-6808
  • DOI: 10.1002/anie.201101905
  • URL: http://dx.doi.org/
  • Peer Reviewed
• [Journal Article] Catalytic Asymmetric Synthesis of Descurainin via 1,3-Dipolar Cycloaddition of a Carbonyl Ylide using Rh_2(R-TCPTTL)_4 (2010)
  • Author(s): Shimada, N.; Hanari, T.; Kurosaki, Y.; Anada, M.; Nambu, H.; Hashimoto, S.
  • Journal Title: Tetrahedron Lett Volume: 51 Issue: 50 Pages: 6572-6575
  • DOI: 10.1016/j.tetlet.2010.10.036
  • Peer Reviewed
• [Journal Article] Catalytic Asymmetric Synthesis of the endo-6-Aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one Natural Product from Ligusticum Chuanxing via 1,3-Dipolar Cycloaddition of a Formyl-Derived Carbonyl Ylide Using Rh_2(S-TCPTTL)_4 (2010)
  • Author(s): Shimada, N.; Hanari, T.; Kurosaki, Y.; Takeda, K.; Anada, M.; Nambu, H.; Shiro, M.; Hashimoto, S.
  • Journal Title: J. Org. Chem. Volume: 75 Issue: 17 Pages: 6039-6042
  • DOI: 10.1021/jo101175b
  • Peer Reviewed
• [Journal Article] A Polymer-Supported Chiral Dirhodium (II) Complex : Highly Durable and Recyclable Catalyst for Asymmetric Intramolecular C-H Insertion Reactions (2010)
  • Author(s): K.Taked, et al
  • Journal Title: Angew.Chem.Int.Ed. Volume: 49 Pages: 6979-6983
  • Peer Reviewed
• [Journal Article] Catalytic Asymmetric Synthesis of the endo-o-6-Aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one Natural Product from Ligusticum Chuanxing via 1,3-Dipolar Cycloaddition of a Formyl-Derived Carbonyl Ylide Using Rh_2(S-TCPTTL)_4 (2010)
  • Author(s): N.Shimada, et al
  • Journal Title: J.Org.Chem. Volume: 75 Pages: 6039-6042
  • Peer Reviewed
• [Journal Article] Catalytic Asymmetric Synthesis of Descurainin via 1,3-Dipolar Cycloaddition of a Carbonyl Ylide Using Rh_2(R-TCPTTL)_4 (2010)
  • Author(s): N.Shimada
  • Journal Title: Tetrahedron Lett. Volume: 51 Pages: 6572-6575
  • Peer Reviewed
• [Journal Article] Catalytic Asymmetric Construction of the exo-7-Aryl-6,8-dioxabicyclo[3.2.1]-octane Framework of Psoracorylifols B and C Using a Carbonyl Ylide Cycloaddition Strategy (2010)
  • Author(s): Y.Kurosaki, et al
  • Journal Title: Bull.Korean Chem.Soc. Volume: 31 Pages: 694-696
  • Peer Reviewed
• [Journal Article] Stereocontrolled Construction of 1,2-cis-α-Glycosidic Linkages Using Glycosyl Diphenyl Phosphates and Synthesis of α-Galactosylceramide KRN7000 (2010)
  • Author(s): H.Nambu
  • Journal Title: Trends Glycosci.Glycotechnol. Volume: 22 Pages: 26-40
  • Peer Reviewed
• [Presentation] コプシロシンAの触媒的不斉全合成研究 (2012)
  • Author(s): 杉原 匠,大原 格,Krishnamurthi Janakiraman, 南部寿則,橋本俊一
  • Organizer: 第38回反応と合成の進歩シンポジウム
  • Place of Presentation: 東京
• [Presentation] Catalytic Enantioselective Intermolecular Cycloaddition of α-Diazo-β-ketoesterDerived Carbonyl Ylides with Phenyl Allenes Using Chiral Dirhodium(II) Carboxylates (2012)
  • Author(s): Krishnamurthi, J.; Nambu, H.; Hashimoto, S.
  • Organizer: The 12th International Kyoto Conference on New Aspects of Organic Chemistry(IKCOC-12)
  • Place of Presentation: Kyoto.
• [Presentation] (+)-コプシロシンAの全合成研究 (2012)
  • Author(s): 大原 格,Krishnamurthi Janakiraman, 杉原匠,南部寿則,橋本俊一
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] Synthetic Studies on Kopsiloscine A Using Asymmetric Intermolecular 1,3-Dipolar Cycloaddition of Carbonyl Ylides (2011)
  • Author(s): Oohara, T.; Krishnamurthi, J.; Nambu, H.; Hashimoto, S.
  • Organizer: 22nd French-Japanese Symposium on Medicinal and Fine Chemistry (FJS-2011)
  • Place of Presentation: Rouen, France
• [Presentation] Catalytic Asymmetric Synthesis of Oxabicyclic Natural Products via 1,3-Dipolar Cycloaddition of Carbonyl Ylides Using Chiral Dirhodium(II) Carboxylates (2011)
  • Author(s): Shimada, N.; Hanari, T.; Anada, M.; Nambu, H.; Hashimoto, S.
  • Organizer: The 23rd International Symposium on Chiral Discrimination (ISCD23)
  • Place of Presentation: Liverpool, United Kingdom.
• [Presentation] Asymmetric Synthesis of Dihydrobenzofuran Natural Products via Intramolecular C-H Insertion Reaction Catalyzed by Chiral Dirhodium (II) Carboxylates (2010)
  • Author(s): Y.Natori, et al
  • Organizer: The 2010 International Chemical Congress of Pacific Basin Societies (Pacifichem 2010)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2010-12-17
• [Book] 不活性結合・不活性分子の活性化：革新的な分子変換反応の開拓（触媒的C－H活性化を機軸とする天然物合成） (2011)
  • Author(s): 穴田仁洋
  • Total Pages: 17
  • Publisher: 化学同人
• [Book] 天然物合成で活躍した反応：実験のコツとポイント（オレフィンクロスメタセシス） (2011)
  • Author(s): 橋本俊一
  • Total Pages: 2
  • Publisher: 化学同人
• [Remarks] 薬品製造化学研究室
  • URL: http://www.pharm.hokudai.ac.jp/yakuzou/index.html