高性能アミン触媒システムの開発

• Project Area: Advanced Molecular Transformations by Organocatalysts
• Project/Area Number: 26105757
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: 田中 富士枝 沖縄科学技術大学院大学, 生体制御分子創製化学ユニット, 准教授 (50260203)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 有機分子触媒 / 有機合成 / 合成化学 / 不斉合成 / エナミン / アミン / 環化反応 / スピロ化合物

Outline of Annual Research Achievements

医薬開発の基になる生物機能分子や、生命機能解明に用いる探索子などを開発、創製するためには、意図する有機分子を自在に合成できるようになることが重要である。特に、医薬などの開発では、一つの最適分子に到達するまで、多様な分子を検討する必要がある。従って、官能基に影響されず、穏和な条件下、安全に、高効率的に、意図する反応点で意図する反応を選択的に行なうことを可能にする方法を開発することが望まれる。本課題では、これらに貢献するよう、アミンを触媒とする有機分子触媒反応を提案し、関連する反応の開発や触媒の開発の基礎となる知見を用意すること、また、実際に有用な方法や触媒システムを用意することを目的とし研究を実施した。
１．不斉ヘテロディールスアルダー反応の開発：最近開発した、エノンとイサチンからスピロオキシインドール構造を有するテトラヒドロピラノン誘導体を合成する不斉ヘテロディールスアルダー反応について、反応経路、立体選択性の制御の機構、優れた反応加速や立体選択性を得るための触媒システムの要件等について検討し明らかにした。また、新たな触媒システムを検討し、反応の応用性を拡張した。
２．無保護糖を基質とする直接的C-グリコシド誘導体合成反応：六員ヘミアセタールを形成する、水酸基無保護の糖（N-アセチルマンノサミン等）を原料とし、穏和な条件下、ワンポットで、形式的にアノメリック炭素上に炭素－炭素結合を生成し、対応するC-グリコシド誘導体を得る、先駆的反応法を開発した。
３．スピロ環を含む多環式化合物を与える不斉反応の開発：２工程で、７つの不斉炭素（その内、２つは四級不斉炭素、１つは四置換不斉炭素）を含む、官能基化されたスピロ環を含む多環式化合物を合成する反応法、およびその触媒システムを開発した。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Synthesis of 4-substituted-pyridine-2,6-dicarboxylic acid derivatives from pyruvates and aldehydes in one pot (2017)
  • Author(s): Chouthaiwale, P. V.; Lapointe, S.; Tanaka, F.
  • Journal Title: Heterocycles Volume: 95 Issue: 1 Pages: 587-594
  • DOI: 10.3987/com-16-s(s)27
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Formal (4+1) Cycloaddition and Enantioselective Michael-Henry-Cascade Reactions to Synthesize Spiro[4,5]decanes and Spirooxindole Polycycles (2017)
  • Author(s): Huang, J.-R.; Sohail, M.; Taniguchi, T.; Monde, K.; Tanaka, F.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 56 Issue: 21 Pages: 5853-5857
  • DOI: 10.1002/anie.201701049
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reaction-based mechanistic investigations of asymmetric hetero-Diels-Alder reactions of enones with isatins catalyzed by amine-based three-component catalyst systems (2016)
  • Author(s): Cui, H.-L., Chouthaiwale, P. V.; Yin, F.; Tanaka, F.
  • Journal Title: Asian J. Org. Chem. Volume: 5 Issue: 1 Pages: 153-161
  • DOI: 10.1002/ajoc.201500412
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Direct synthesis of C-glycosides from unprotected 2-N-acyl-aldohexoses via aldol condensation-oxa-Michael reactions with unactivated ketones (2016)
  • Author(s): Johnson, S.; Tanaka, F.
  • Journal Title: Org. Biomol. Chem. Volume: 14 Issue: 1 Pages: 259-264
  • DOI: 10.1039/c5ob02094h
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Catalytic asymmetric hetero-Diels-Alder reactions of enones with isatins to access functionalized spirooxindole tetrahydropyrans: Scope, derivatization, and discovery of bioactives (2016)
  • Author(s): Cui, H.-L.; Chouthaiwale, P. V.; Yin, F.; Tanaka, F.
  • Journal Title: Org. Biomol. Chem. Volume: 14 Issue: 5 Pages: 1777-1783
  • DOI: 10.1039/c5ob02393a
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Catalytic enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones (2016)
  • Author(s): Zhang, D.; Tanaka, F.
  • Journal Title: RSC Advances Volume: 6 Issue: 66 Pages: 61454-61457
  • DOI: 10.1039/c6ra13859d
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Discovery of SOAT2 Inhibitors from Synthetic Small Molecules (2016)
  • Author(s): Kobayashi, K.; Ohshiro, T.; Tomoda, H.; Yin, F.; Cui, H.-L.; Chouthaiwale, P. V.; Tanaka, F.
  • Journal Title: Bioorg. Med. Chem Lett. Volume: 26 Issue: 24 Pages: 5899-5901
  • DOI: 10.1016/j.bmcl.2016.11.008
  • Peer Reviewed
• [Journal Article] Aldol reactions of ketone donors with aryl trifluoromethyl ketone acceptors catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) for concise access to aryl- and trifluoromethyl-substituted tertiary alcohols (2015)
  • Author(s): Zhang, D.; Tanaka, F.
  • Journal Title: Adv. Synth. Catal. Volume: 357 Issue: 16-17 Pages: 3458-3462
  • DOI: 10.1002/adsc.201500497
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Aldol reactions of 1,2-diketones catalyzed by amines to afford furanose derivatives (2015)
  • Author(s): Jithender, E.; Katsuyama, I.; Zhang, D.; Johnson, S.; Tanaka, F.
  • Journal Title: Tetrahedron Lett. Volume: 56 Issue: 5 Pages: 735-738
  • DOI: 10.1016/j.tetlet.2014.12.094
  • Peer Reviewed
• [Journal Article] 高性能アミン触媒システムの開発：求核剤および親電子剤となる分子の反応の制御 (2015)
  • Author(s): 田中富士枝
  • Journal Title: 有機分子触媒による未来型分子変換 News Letter Volume: -
• [Journal Article] Synthesis of furanose spirooxindoles via 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed aldol reactions of a pyruvic aldehyde derivative (2014)
  • Author(s): Zhang, D.; Johnson, S.; Cui, H.-L.; Tanaka, F.
  • Journal Title: Asian J. Org. Chem. Volume: 3 Issue: 4 Pages: 391-394
  • DOI: 10.1002/ajoc.201400016
  • Peer Reviewed / Open Access
• [Journal Article] One-pot synthesis of polysubstituted 3-acylpyrroles by cooperative catalysis (2014)
  • Author(s): Cui, H.-L.; Tanaka, F.
  • Journal Title: Org. Biomol. Chem. Volume: 12 Issue: 31 Pages: 5822-5826
  • DOI: 10.1039/c4ob01019a
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reactions of pyruvates: organocatalytic synthesis of functionalized dihydropyrans in one pot and further transformations to functionalized carbocycles and heterocycles (2014)
  • Author(s): Chouthaiwale, P. V.; Tanaka, F.
  • Journal Title: Chem. Commun. Volume: 50 Issue: 94 Pages: 14881-14884
  • DOI: 10.1039/c4cc06035k
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Synthesis of iminosugar C-glycosides via Mannich-aminocyclization reactions (2017)
  • Author(s): Maram, L.; 田中富士枝
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台市
  • Year and Date: 2017-03-24
• [Presentation] Organocatalytic reactions for the synthesis of functionalized molecules (2017)
  • Author(s): 田中富士枝
  • Organizer: 第７回生体分子科学シンポジウム
  • Place of Presentation: 大阪府
  • Invited
• [Presentation] Construction of aryl- and trifluoromethyl-substituted tertiary alcohols via aldol reactions catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (2016)
  • Author(s): Zhang, D.; Tanaka, F.
  • Organizer: ICOS 21, 21st International Conference on Organic Synthesis
  • Place of Presentation: Mumbai, India
  • Year and Date: 2016-12-11
  • Int'l Joint Research
• [Presentation] Deuteration studies of DBU-catalyzed aldol reactions, in The 9th Symposium on Organocatalysis (2016)
  • Author(s): Zhang, D.; 田中富士枝
  • Organizer: 第9回有機触媒シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2016-12-01
• [Presentation] Catalytic enantioselective hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones to give trifluoromethyl-substituted tetrahydropyranones (2016)
  • Author(s): Zhang, D.; Tanaka, F.
  • Organizer: Molecular Chirality Asia 2016
  • Place of Presentation: 大阪市
  • Year and Date: 2016-04-20
  • Int'l Joint Research
• [Presentation] Synthesis of iminosugar C-glycosides via a Mannich reaction-aminocyclization route (2016)
  • Author(s): Maram, L.; Tanaka, F.
  • Organizer: Molecular Chirality Asia 2016
  • Place of Presentation: 大阪市
  • Year and Date: 2016-04-20
  • Int'l Joint Research
• [Presentation] Synthesis of 3-pyrrolidinecarboxylic acids via enantioselective organocatalytic Michael addition of nitroalkanes to 4-oxopent-2-enoate derivatives (2016)
  • Author(s): Yin, F.; 田中富士枝
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-26
• [Presentation] Synthesis and application of analogs of 1,8-siazabicyclo[5.4.0]undec-7-ene (DBU) (2016)
  • Author(s): Sohail, M.; Zhang, D.; 田中富士枝
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-26
• [Presentation] Construction of aryl- and trifluoromethyl-substituted tertiary alcohols via aldol reactions catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (2016)
  • Author(s): Zhang, D.; Tanaka, F.
  • Organizer: ISACS19: Challenges in Organic Chemistry
  • Place of Presentation: Irvine, USA
  • Year and Date: 2016-03-20
  • Int'l Joint Research
• [Presentation] 高性能アミン触媒システムの開発 (2016)
  • Author(s): 田中富士枝
  • Organizer: 「有機分子触媒による未来型分子変換」第6回公開シンポジウム
  • Place of Presentation: 大阪市
  • Year and Date: 2016-01-22
• [Presentation] DBU-catalyzed regioselective aldol reactions to synthesize functionalized molecules with tetrasubstituted carbon centers (2015)
  • Author(s): Zhang, D.; Tanaka, F.
  • Organizer: The 38th Naito Conference The Chemistry of Organocatalysts
  • Place of Presentation: 札幌市
  • Year and Date: 2015-07-06
  • Int'l Joint Research
• [Presentation] 新規生物活性分子創製に貢献する分子合成 (2015)
  • Author(s): 田中富士枝
  • Organizer: 第43回日本潰瘍学会
  • Place of Presentation: 沖縄県
  • Year and Date: 2015-06-19
  • Invited
• [Presentation] Stereoselective synthesis of C-glycosides from unprotected C6 aldopyranoses via amine-catalyzed aldol condensation-oxa-Michael addition reactions (2015)
  • Author(s): Johnson, S.; Tanaka, F.
  • Organizer: 第8回有機触媒シンポジウム 兼「有機分子触媒による未来型分子変換」第5回公開シンポジウム
  • Place of Presentation: 那覇市
  • Year and Date: 2015-05-10
• [Presentation] Synthesis of furanose derivatives via amine-catalyzed aldol reactions of 1,2-diketones (2015)
  • Author(s): エヌコンダジテンダー, 勝山勇, 張冬欣, Sherida Johnson, 田中富士枝
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Organocatalytic tandem aldol condensation-Michael reactions of C6 pyranoses to synthesize C-glycosides (2015)
  • Author(s): Sherida Johnson, 田中富士枝
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Aldol reactions using aryltrifluoromethyl ketones as electrophiles catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under solvent free mild conditions (2015)
  • Author(s): 張冬欣, 田中富士枝
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 合成化合物ライブラリからの骨形成因子シグナル阻害剤に関する研究 (2015)
  • Author(s): 諏訪いぶき、内田龍児、Hai-Lei Cui、Pandurang V. Chowthaiwale、田中富士枝、片桐岳信、供田洋
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 活性物質スクリーニング用糖誘導体の合成 (2015)
  • Author(s): 田中富士枝
  • Organizer: 「知的クラスター形成に向けた研究拠点構築事業」沖縄の生物資源とネットワークを活用した医薬品探索研究、平成26年度第二回研究推進委員会
  • Place of Presentation: 那覇市
  • Year and Date: 2015-01-09
• [Presentation] Cooperative catalysis: synthesis of 3-acylpyrroles and 2,5-dihydropyrroles via aza-Michael-alkyne carbocyclization cascade from enones and propargylamines (2014)
  • Author(s): Cui, H.-L.; Tanaka, F.
  • Organizer: 平成26年度「知的クラスター形成に向けた研究拠点構築事業」シンポジウム
  • Place of Presentation: 那覇市
  • Year and Date: 2014-12-18
• [Presentation] Asymmetric formal oxa-Diels-Alder reaction catalyzed by amine-based catalysts affording functionalized spirooxindole tetrahydropyrans (2014)
  • Author(s): Cui, H.-L.; Tanaka, F.
  • Organizer: 平成26年度「知的クラスター形成に向けた研究拠点構築事業」シンポジウム
  • Place of Presentation: 那覇市
  • Year and Date: 2014-12-18
• [Presentation] Organocatalytic aldol reactions of C6 pyranoses to synthesize C9 sugars (2014)
  • Author(s): Johnson, S.; Tanaka, F.
  • Organizer: 平成26年度「知的クラスター形成に向けた研究拠点構築事業」シンポジウム
  • Place of Presentation: 那覇市
  • Year and Date: 2014-12-18
• [Presentation] β-Proline-catalyzed reactions of pyruvates to synthesize functionalized molecules (2014)
  • Author(s): Chouthaiwale, P. V.; Tanaka
  • Organizer: 平成26年度「知的クラスター形成に向けた研究拠点構築事業」シンポジウム
  • Place of Presentation: 那覇市
  • Year and Date: 2014-12-18
• [Presentation] Synthesis of spirooxindole furanose derivatives via DBU-catalyzed aldol reactions (2014)
  • Author(s): Zhang, D.; Johnson, S.; Cui, H.-L.; Tanaka, F.
  • Organizer: 平成26年度「知的クラスター形成に向けた研究拠点構築事業」シンポジウム
  • Place of Presentation: 那覇市
  • Year and Date: 2014-12-18
• [Presentation] β-Proline-catalyzed reactions of pyruvates to synthesize functionalized molecules (2014)
  • Author(s): Chouthaiwale, P. V.; Tanaka, F.
  • Organizer: Advanced Molecular Transformations by Organocatalysts 2nd International Conference and 7th Symposium on organocatalysis
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] Asymmetric formal oxa-Diels Alder reaction catalyzed by amine-based catalysts affording functionalized spirooxindole tetrahydropyrans (2014)
  • Author(s): Cui, H.-L.; Tanaka, F.
  • Organizer: The 14th Belgian Organic Synthesis Symposium
  • Place of Presentation: Louvain-la-Neuve, Belgium
  • Year and Date: 2014-07-13 – 2014-07-18
• [Presentation] Synthesis of spirooxindole furanose derivatives via DBU-catalyzed aldol reactions (2014)
  • Author(s): Zhang, D. Johnson, S., Cui, H.; Tanaka, F.
  • Organizer: The 14th Belgian Organic Synthesis Symposium
  • Place of Presentation: Louvain-la-Neuve, Belgium
  • Year and Date: 2014-07-13 – 2014-07-18
• [Presentation] 活性物質スクリーニング用糖誘導体の合成 (2014)
  • Author(s): 田中富士枝
  • Organizer: 知的クラスター形成に向けた研究拠点構築事業」沖縄の生物資源とネットワークを活用した医薬品探索研究、平成26年度第一回研究推進委員会
  • Place of Presentation: 那覇市
  • Year and Date: 2014-06-09
• [Presentation] 不斉ヘテロ-ディールス-アルダー反応： スピロ置換オキシインドール基を有するテトラヒドロピラノン誘導体の合成 (2014)
  • Author(s): Cui, H.-L.; 田中富士枝
  • Organizer: 文科省新学術領域研究 • がん支援「化学療法基盤支援活動」第３回シンポジウム アカデミアからの抗がん剤創薬に向けて天然物の有効利用
  • Place of Presentation: 名護市、沖縄県
  • Year and Date: 2014-05-12
• [Book] CSJ カレントレビュー 22 有機分子触媒の化学 (Chapter 2 酵素と有機分子触媒) (2016)
  • Author(s): 田中富士枝
  • Publisher: 化学同人
• [Remarks] FY2014 Annual Report
  • URL: https://groups.oist.jp/ccbe/fy2014-annual-report
• [Remarks] FY2015 Annual Report
  • URL: https://groups.oist.jp/ccbe/fy2015-annual-report
• [Remarks] FY2013 Annual Report
  • URL: https://groups.oist.jp/ccbe/fy2013-annual-report
• [Patent(Industrial Property Rights)] C-Glycoside derivatives (2016)
  • Inventor(s): Tanaka, F.; Johnson, S.
  • Industrial Property Rights Holder: 沖縄科学技術大学院大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-02-01
  • Overseas
• [Patent(Industrial Property Rights)] 5-Substituted-5-hydroxy-5-aryl-3-oxo-pentanoate derivatives and their enantiopure forms (2016)
  • Inventor(s): Tanaka, F.; Zhang, D.
  • Industrial Property Rights Holder: 沖縄科学技術大学院大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-02-01
  • Overseas
• [Patent(Industrial Property Rights)] Pyridine-2,6-dicarboxylic acid derivatives (2014)
  • Inventor(s): Chouthaiwale, P. V.; Tanaka, F.
  • Industrial Property Rights Holder: 学校法人沖縄科学技術大学院大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-09-09
  • Overseas