Development and Application of Regio- and Stereoselective beta-Mannosylation Utilizing Organoboron Reagents

• Project/Area Number: 16K05781
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: Keio University
• Principal Investigator: Takahashi Daisuke 慶應義塾大学, 理工学部(矢上), 准教授 (00509929)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: グリコシル化反応 / β-マンノシド / 配糖体 / 天然糖脂質 / ボロン酸 / ボリン酸 / 位置選択的 / 立体選択的 / 糖鎖 / β-ラムノシド / 有機ホウ素化合物 / 立体特異的 / 無保護糖 / マンノースエリスリトールリピッド / 構造活性相関 / 糖脂質 / 天然物 / 天然物合成 / β-マンノシル化反応 / 有機ホウ素分子

Outline of Final Research Achievements

Novel stereoselective beta-mannosylation using 1,2-anhydromannose donor and borinic acid catalyst was developed. In addition, regio- and stereoselective beta-mannosylation using boronic acid catalyst was also developed. Furthermore, these methods were successfully applied to the total synthesis of biologically active natural glycolipids.

Academic Significance and Societal Importance of the Research Achievements

本研究では、有機ホウ素化合物の化学的特性を利用することで、立体選択的な構築が最も困難な結合様式の一つであるβ-マンノシドを、高い位置及び立体選択性で合成可能にする新手法の開発と、本手法を用いた天然糖脂質を含む種々の有用糖質の合成に成功した。そのため本手法は、様々な生物活性糖鎖や配糖体天然物の効率的な合成への応用が期待され、糖質が関与する生命現象や疾病のメカニズム解明、さらには、糖質を標的とした予防・診断・治療薬の創製に大きく貢献すると予想できる。以上の点から、本研究成果の意義は大きく、今後の学術面のみならず社会における貢献度も大きいと言える。

Research Products

• [Journal Article] 2-PhenylquinolineーSugar Hybrids as Photo-switchable α-Glucosidase Inhibitors (2019)
  • Author(s): T. Kitamura, M. Okuyama, *D. Takahashi, *K. Toshima
  • Journal Title: Chemistry An Asian Journal Volume: - Issue: 9 Pages: 1409-1412
  • DOI: 10.1002/asia.201900203
  • Peer Reviewed
• [Journal Article] Regioselective and Stereoselective Glycosylations Utilizing Organoboron Compounds (2018)
  • Author(s): *D. Takahashi, M. Tanaka, *K. Toshima
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 30 Issue: 174 Pages: E55-E62
  • DOI: 10.4052/tigg.1817.2E
  • NAID: 130006744106
  • ISSN: 0915-7352, 1883-2113
  • Year and Date: 2018-05-25
  • Peer Reviewed
• [Journal Article] Borinic Acid Catalyzed 1,2-cis-Stereoselective Glycosylations and Their Applications to the Total Synthesis of Natural Products (2018)
  • Author(s): *高橋大介
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 76 Issue: 5 Pages: 470-473
  • DOI: 10.5059/yukigoseikyokaishi.76.470
  • NAID: 130006733907
  • ISSN: 0037-9980, 1883-6526
  • Year and Date: 2018-05-01
  • Peer Reviewed
• [Journal Article] Stereospecific β-L-Rhamnopyranosylation through an SNi-Type Mechanism by Using Organoboron Reagents (2018)
  • Author(s): N. Nishi, K. Sueoka, K. Iijima, R. Sawa, *D. Takahashi, *K. Toshima
  • Journal Title: Angewandte Chemie International Edition Volume: 57 Issue: 42 Pages: 13858-13862
  • DOI: 10.1002/anie.201808045
  • Peer Reviewed
• [Journal Article] Novel Hemagglutinin-Binding Sulfated Oligofucosides and Their Effect on Influenza Virus Infection (2018)
  • Author(s): S. Kosono, A. Kasai, S. Komaba, T. Matsubara, T. Sato, *D. Takahashi, *K. Toshima
  • Journal Title: Chemical Communications Volume: 54 Issue: 54 Pages: 7467-7470
  • DOI: 10.1039/c8cc03865a
  • Peer Reviewed
• [Journal Article] An AnthraquinoneーEnzymeーPeptide Hybrid as a Photo-Switchable Enzyme (2018)
  • Author(s): S. Sotokawa, T. Kitamura, D. Takahashi, *K. Toshima
  • Journal Title: Chemical Communications Volume: 54 Issue: 75 Pages: 10614-10617
  • DOI: 10.1039/c8cc06130k
  • Peer Reviewed
• [Journal Article] Systematic and Stereoselective Total Synthesis of Mannosylerythritol Lipids and Evaluation of Their Antibacterial Activity (2018)
  • Author(s): Nashida Junki、Nishi Nobuya、Takahashi Yoshiaki、Hayashi Chigusa、Igarashi Masayuki、Takahashi Daisuke、Toshima Kazunobu
  • Journal Title: The Journal of Organic Chemistry Volume: - Issue: 13 Pages: 7281-7289
  • DOI: 10.1021/acs.joc.8b00032
  • Peer Reviewed
• [Journal Article] Boronic-Acid-Catalyzed Regioselective and 1,2-cis-Stereoselective Glycosylation of Unprotected Sugar Acceptors via SNi-Type Mechanism (2018)
  • Author(s): Tanaka Masamichi、Nakagawa Akira、Nishi Nobuya、Iijima Kiyoko、Sawa Ryuichi、Takahashi Daisuke、Toshima Kazunobu
  • Journal Title: Journal of the American Chemical Society Volume: 140 Issue: 10 Pages: 3644-3651
  • DOI: 10.1021/jacs.7b12108
  • Peer Reviewed
• [Journal Article] Novel 1,2-cis-Stereoselective Glycosylations Utilizing Organoboron Reagents and Their Application to Natural Products and Complex Oligosaccharide Synthesis (2017)
  • Author(s): Takahashi Daisuke、Tanaka Masamichi、Nishi Nobuya、Toshima Kazunobu
  • Journal Title: Carbohydrate Research Volume: 452 Pages: 64-77
  • DOI: 10.1016/j.carres.2017.10.004
  • Peer Reviewed
• [Journal Article] Target-Selective Fluorescence Imaging and Photocytotoxicity against H2O2 High-Expressing Cancer Cells Using a Photoactivatable Theranostic Agent (2017)
  • Author(s): Takagi Ryoma、Takeda Ayano、Takahashi Daisuke、Toshima Kazunobu
  • Journal Title: Chemistry An Asian Journal Volume: 12 Issue: 20 Pages: 2656-2659
  • DOI: 10.1002/asia.201701004
  • Peer Reviewed
• [Journal Article] Regio- and Stereoselective β-Mannosylation Using a Boronic Acid Catalyst and Its Application to the Synthesis of a Tetrasaccharide Repeating Unit of Lipopolysaccharide Derived from E. Coli O75 (2017)
  • Author(s): N. Nishi, J. Nashida, E. Kaji, D. Takahashi, K. Toshima
  • Journal Title: Chemical Communications Volume: 53 Issue: 21 Pages: 3018-3021
  • DOI: 10.1039/c7cc00269f
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 1,2-cis-α-Stereoselective Glycosylation Utilizing a Glycosyl-Acceptor-Derived Boronic Ester and Its Application to the Total Synthesis of Natural Glycosphingolipids (2016)
  • Author(s): M. Tanaka, D. Takahashi, K. Toshima
  • Journal Title: Organic Letters Volume: 18 Issue: 19 Pages: 5030-5033
  • DOI: 10.1021/acs.orglett.6b02488
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glycosyl-Acceptor-Derived Boronic Ester-Promoted Direct and β-Stereoselective Mannosylation with a 1,2-Anhydromannose Donor (2016)
  • Author(s): M. Tanaka, J. Nashida, D. Takahashi, K. Toshima
  • Journal Title: Organic Letters Volume: 18 Issue: 9 Pages: 2288-2291
  • DOI: 10.1021/acs.orglett.6b00926
  • Peer Reviewed
• [Journal Article] 有機ホウ素化合物を利用した標的糖鎖の選択的合成と光分解 (2016)
  • Author(s): 高橋大介
  • Journal Title: 化学と工業 Volume: 69 Pages: 881-882
• [Presentation] 有機ホウ素化合物を用いた立体特異的β-ラムノシル化反応の開発と反応機構解析 (2019)
  • Author(s): 西 信哉、末岡 和博、高橋 大介、戸嶋 一敦
  • Organizer: 日本化学会第99春季年会
• [Presentation] Boronic acid catalyzed desymmetric 1,2-cis-glycosylation of meso-diols (2019)
  • Author(s): Masamichi Tanaka, Koji Sato, Ryoki Yoshida, Daisuke Takahashi, Kazunobu Toshima
  • Organizer: 日本化学会第99春季年会
• [Presentation] 細胞表面糖鎖修飾によるがん細胞の補体依存性細胞死誘導 (2019)
  • Author(s): 芳上 慎悟、志村 拓海、高橋 大介、戸嶋 一敦
  • Organizer: 日本化学会第99春季年会
• [Presentation] 天然糖脂質テルピオシドBの全合成研究 (2019)
  • Author(s): 遠藤 正人、稲葉 和樹、飯淵 直人、高橋 大介、戸嶋 一敦
  • Organizer: 日本化学会第99春季年会
• [Presentation] Boronic-Acid-Catalyzed Regio- and 1,2-cis-Stereoselective Glycosylation (2019)
  • Author(s): Daisuke Takahashi
  • Organizer: KEIO International Symposium on Innovative Molecular Transformations
  • Int'l Joint Research / Invited
• [Presentation] Stereospecific β-L-Rhamnosylation Using Organoboron Reagents via SNi-Type Mechanism (2018)
  • Author(s): Daisuke Takahashi, Nobuya Nishi, Kazuhiro Sueoka, Kazunobu Toshima
  • Organizer: The 14th Keio LCC-Yonsei CBMH Joint Symposium
  • Int'l Joint Research
• [Presentation] ボロン酸触媒を用いた無保護糖に対する位置及び立体選択的グリコシル化反応の開発と応用 (2018)
  • Author(s): 田中 将道、中川 彰、西 信哉、高橋 大介、戸嶋 一敦
  • Organizer: 第60回天然有機化合物討論会
• [Presentation] 有機ホウ素化合物を用いたSNi型立体特異的β-ラムノシル化反応の開発 (2018)
  • Author(s): 西 信哉、末岡 和博、高橋 大介、戸嶋 一敦
  • Organizer: 第35回有機合成セミナー
• [Presentation] マンノシルエリスリトールリピッド類の系統的全合成とベシクル形成能評価 (2018)
  • Author(s): 高橋 大介、舩越 桃子、梨子田 淳希、西 信哉、伴野 太祐、朝倉 浩一、戸嶋 一敦
  • Organizer: 日本油化学会第57回年会
• [Presentation] マンノシルエリスリトールリピッド類の系統的全合成と抗菌活性 (2018)
  • Author(s): 舩越 桃子、梨子田 淳希、西 信哉、高橋 良昭、林 千草、五十嵐 雅之、高橋 大介、戸嶋 一敦
  • Organizer: 第37回日本糖質学会年会
• [Presentation] Boronic Acid Catalyzed Regio-and 1,2-cis-Stereoselective Glycosylation of Unprotected Sugar Acceptors via SNi-Type Mechanism (2018)
  • Author(s): Daisuke Takahashi, Masamichi Tanaka, Akira Nakagawa, Nobuya Nishi, Kazunobu Toshima
  • Organizer: The 29th International Carbohydrate Symposium
  • Int'l Joint Research
• [Presentation] APPLICATION OF BORONIC-ACID-CATALYZED GLYCOSYLATION TO LATE-STAGE MODIFICATION OF NATURAL GLYCOSIDES AND OLIGOSACCHARIDE SYNTHESIS (2018)
  • Author(s): Masamichi Tanaka, Akira Nakagawa, Nobuya Nishi, Daisuke Takahashi, Kazunobu Toshima
  • Organizer: The 29th International Carbohydrate Symposium
  • Int'l Joint Research
• [Presentation] 無保護の天然配糖体に対するボロン酸触媒を用いた直接的な位置及び1,2-cis-立体選択的グリコシル化反応の開発 (2018)
  • Author(s): 吉田 亮毅、田中 将道、高橋 大介、戸嶋 一敦
  • Organizer: 日本化学会第９８春季年会
• [Presentation] マンノシルエリスリトールリピッド類(MELs)の系統的合成とベシクル形成に与える効果 (2018)
  • Author(s): 梨子田 淳希、西 信哉、伴野 太祐、朝倉 浩一、高橋 大介、戸嶋 一敦
  • Organizer: 日本化学会第９８春季年会
• [Presentation] ボリン酸―糖受容体エステルを用いた立体選択的β-ラムノシル化反応の開発 (2018)
  • Author(s): 末岡 和博、西 信哉、高橋 大介、戸嶋 一敦
  • Organizer: 日本化学会第９８春季年会
• [Presentation] 有機ホウ素化合物の化学的特性を活用した糖質化学の新展開 (2018)
  • Author(s): 高橋 大介
  • Organizer: 東レ株式会社医薬研究所 有機合成化学講座
  • Invited
• [Presentation] 有機ホウ素化合物を利用した大腸菌由来糖鎖の位置および立体選択的合成研究 (2017)
  • Author(s): 梨子田淳希、西信哉、梶英輔、高橋大介、戸嶋一敦
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学（神奈川県、横浜市）
  • Year and Date: 2017-03-16
• [Presentation] Regio- and Stereoselective Glycosylation of Unprotected Sugar Acceptors Using Boronic Acid Catalyst and Its Application to the Synthesis of Biologically Active Glycosides (2017)
  • Author(s): M. Tanaka, A. Nakagawa, D. Takahashi, K. Toshima
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学（神奈川県、横浜市）
  • Year and Date: 2017-03-16
• [Presentation] Development and Application of Boronic Acid Catalyzed Regio- and 1,2-cis-Stereoselective Glycosylation of Unprotected Sugar Acceptors (2017)
  • Author(s): Daisuke Takahashi, Masamichi Tanaka, Akira Nakagawa, Nobuya Nishi, Kazunobu Toshima
  • Organizer: 9th Asian Community of Glycoscience and Glycotechnology Conference
  • Int'l Joint Research
• [Presentation] Development and Application of Boronic Acid Catalyzed Regio- and Stereoselective β-Mannosylation (2017)
  • Author(s): Nobuya Nishi, Junki Nashida, Eisuke Kaji, Daisuke Takahashi, Kazunobu Toshima
  • Organizer: The 11th International Symposium on Integrated Synthesis (ISONIS-11) & The 3rd International Symposium on Middle Molecular Strategy (ISMMS-3)
  • Int'l Joint Research
• [Presentation] Boronic Acid Catalyzed Regio- and 1,2-cis-α-Stereoselective Glycosylation of Unprotected Sugar Acceptors and Its Application to the Synthesis of Biologically Active Glycosides (2017)
  • Author(s): Daisuke Takahashi, Masamichi Tanaka, Akira Nakagawa, Kazunobu Toshima
  • Organizer: The 13th Yonsei CBMH - Keio LCC Joint Symposium 2017
  • Int'l Joint Research
• [Presentation] 糖質の精密合成・機能解析・機能制御分子の創製に関する研究 (2017)
  • Author(s): 高橋 大介
  • Organizer: 第34回有機合成化学セミナー
  • Invited
• [Presentation] ボロン酸触媒を用いた位置及び立体選択的1,2-cis-β-グリコシル化反応の開発 (2017)
  • Author(s): 西 信哉、梨子田 淳希、梶 英輔、高橋 大介、戸嶋 一敦
  • Organizer: 第３６回 日本糖質学会年会
• [Presentation] New Glycosylation Method Using Glycosyl-Acceptor-Derived Boronic Ester Catalyst and lts Application to Total Synthesis of a Natural Product (2016)
  • Author(s): D. Takahashi, M. Tanaka, K. Toshima
  • Organizer: The 12th Keio LCC - Yonsei CBMH Joint Symposium, Yagami campus, Keio University
  • Place of Presentation: 慶應義塾大学（神奈川県、横浜市）
  • Year and Date: 2016-10-21
  • Int'l Joint Research
• [Presentation] ボロン酸触媒を用いた無保護糖受容体に対する位置及び立体選択的グリコシル化反応の開発 (2016)
  • Author(s): 中川彰、田中将道、高橋 大介、戸嶋 一敦
  • Organizer: 第３５回 日本糖質学会年会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県、高知市）
  • Year and Date: 2016-09-01
• [Presentation] 有機ボロン酸の化学的特性を駆使した標的糖鎖の選択的合成と光分解に関する研究 (2016)
  • Author(s): 高橋大介
  • Organizer: 第３５回 日本糖質学会年会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県、高知市）
  • Year and Date: 2016-09-01
  • Invited
• [Presentation] 有機ホウ素化合物を活用した糖質科学の新展開 (2016)
  • Author(s): 高橋大介
  • Organizer: 第12回機能性糖鎖講演会
  • Place of Presentation: 鳥取大学（鳥取県、鳥取市）
  • Invited
• [Presentation] ボロン酸触媒を用いた位置及び立体選択的β-マンノシル化反応の開発と大腸菌由来糖鎖合成への応用 (2016)
  • Author(s): 西 信哉、梨子田淳希、高橋 大介、戸嶋一敦
  • Organizer: Glyco TOKYO 2016シンポジウム
  • Place of Presentation: 東京工業大学（東京都、目黒区）
• [Presentation] 有機ホウ素化合物を活用した標的糖質の選択的合成と光分解 (2016)
  • Author(s): 高橋大介
  • Organizer: 第4回慶應有機化学若手シンポジウム
  • Place of Presentation: 慶應義塾大学（神奈川県、横浜市）
  • Invited
• [Remarks] 分子生命化学研究室
  • URL: http://www.applc.keio.ac.jp/~toshima/takahashi.html
• [Remarks] β-ラムノシドを精密に合成する新手法の開発－病原菌由来糖鎖合成を簡便に、ワクチン開発への応用に期待－
  • URL: https://www.keio.ac.jp/ja/press-releases/2018/8/31/28-47621/
• [Remarks] 高橋 大介 准教授 - Toshima Lab.
  • URL: http://www.applc.keio.ac.jp/~toshima/takahashi.html
• [Remarks]
  • URL: http://www.applc.keio.ac.jp/~toshima/takahashi.html