Synthetic study of polycyclic natural products having adjacent quaternary asymmetric carbon atoms toward the understanding of their biological effects

• Project/Area Number: 24510290
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Hokkaido University
• Principal Investigator: YOSHIMURA Fumihiko 北海道大学, 理学(系)研究科(研究院), 助教 (70374189)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 全合成 / ブラシリカルジン / アンドラスチン / ニトリル / ニトロン / 四級不斉炭素 / N-シリルケテンイミン / ブラシリカルジンA / 共役付加反応 / 立体選択的合成 / テルペン / アンドラスチンC / ワインレブアミド / セミピナコール転位 / ヒドロキシルアミン

Outline of Final Research Achievements

This research aimed at total syntheses of Brasilicardin A and Andrastin C that belong to biologically active natural products with adjacent and/or contiguous quaternary asymmetric carbon atoms on their polycyclic frameworks. To achieve this goal, we developed an efficient synthetic method for stereoselective construction of a quaternary asymmetric carbon atom through an intramolecular conjugate addition reaction of α-cyano carbanion. By using this method as key reactions, we succeeded in the synthesis of methyl ester of Brasilicardin A aglycon. Additionally, novel nucleophilic addition reactions of nitriles to nitrones under mild silylation conditions were developed.

Research Products

• [Journal Article] Nucleophilic Addition Reactions of Nitriles to Nitrones under Mild Silylation Conditions (2014)
  • Author(s): Fumihiko Yoshimura, Taiki Abe, and Keiji Tanino
  • Journal Title: Synlett Volume: 25 Issue: 13 Pages: 1863-1868
  • DOI: 10.1055/s-0034-1378274
  • NAID: 120005647261
  • Peer Reviewed / Open Access
• [Journal Article] Recent developments in the synthesis of zoanthamine alkaloids (2014)
  • Author(s): Fumihiko Yoshimura, Keiji Tanino, Masaaki Miyashita
  • Journal Title: Tetrahedron Letters Volume: 55 Issue: 18 Pages: 2895-2903
  • DOI: 10.1016/j.tetlet.2014.03.073
  • NAID: 120005455895
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Synthesis of 2-Cyano-1,4-cycloheptadiene Derivatives via Divinylcyclopropane Rearrangement and Alkylation of Novel Cycloheptadienyl Anion Species (2013)
  • Author(s): Takumasa Yamada, Fumihiko Yoshimura, Keiji Tanino
  • Journal Title: Tetrahedron Letters Volume: 54 Issue: 6 Pages: 522-525
  • DOI: 10.1016/j.tetlet.2012.11.070
  • Peer Reviewed
• [Journal Article] Chemical Synthesis of Zoanthamine Alkaloids (2013)
  • Author(s): 吉村文彦、谷野圭持、宮下正昭
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 71 Issue: 2 Pages: 124-135
  • DOI: 10.5059/yukigoseikyokaishi.71.124
  • NAID: 10031148204
  • ISSN: 0037-9980, 1883-6526
  • Peer Reviewed
• [Journal Article] Stereocontrolled synthesis of Carbocyclic Compounds with a Quaternary Carbon Atom based on SN2' Alkylation of γ,δ-Epoxy-α,β-unsaturated Ketones (2012)
  • Author(s): 谷野圭持、吉村文彦, ほか1名
  • Journal Title: Organic & Biomolecular Chemistry Volume: 10 Issue: 28 Pages: 5431-5442
  • DOI: 10.1039/c2ob25719j
  • NAID: 120005228736
  • Peer Reviewed
• [Journal Article] Total Synthesis of Zoanthamine Alkaloids (2012)
  • Author(s): F. Yoshimura, K. Tanino, and M. Miyashita
  • Journal Title: Acc. Chem. Res Volume: 45 (5) Issue: 5 Pages: 746-755
  • DOI: 10.1021/ar200267a
  • Peer Reviewed
• [Presentation] ブラシリカルジンAアグリコンの不斉合成研究 (2015)
  • Author(s): 伊東龍生、鳥塚誠、森元気、吉村文彦、谷野圭持
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（習志野市）
  • Year and Date: 2015-03-28
• [Presentation] o-ビニルベンジルシアニドの分子内環化反応による2-ナフチルアミン誘導体の新規合成法 (2015)
  • Author(s): 阿部泰樹、吉村文彦、谷野圭持
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（習志野市）
  • Year and Date: 2015-03-27
• [Presentation] ローラレンの全合成研究 (2015)
  • Author(s): 岡田拓、吉村文彦、谷野圭持
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（習志野市）
  • Year and Date: 2015-03-26
• [Presentation] ブラシリカルジンAの不斉全合成研究 (2014)
  • Author(s): 伊東龍生、鳥塚誠、森元気、吉村文彦、谷野圭持
  • Organizer: 第55回香料・テルペンおよび精油化学に関する討論会
  • Place of Presentation: 和歌山大学（和歌山市）
  • Year and Date: 2014-09-20
• [Presentation] Brasilicardin Aの不斉全合成研究 (2014)
  • Author(s): 伊東龍生、鳥塚誠、吉村文彦、谷野圭持
  • Organizer: 日本化学会北海道支部2014年夏季研究発表会
  • Place of Presentation: 苫小牧高等専門学校（苫小牧市）
  • Year and Date: 2014-07-12
• [Presentation] 温和なシリル化条件下のニトリル誘導体とニトロンの求核付加反応
  • Author(s): 阿部泰樹、吉村文彦、谷野圭持
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（名古屋市）
• [Presentation] アンドラスチンCの全合成研究
  • Author(s): 石岡悠一、山田拓正、吉村文彦、谷野圭持
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（名古屋市）
• [Presentation] 四級不斉炭素の立体選択的構築法の開発と天然物全合成への展開
  • Author(s): 吉村文彦
  • Organizer: 平成25年度日本化学会北海道支部奨励賞受賞講演
  • Place of Presentation: 北海道大学（札幌市）
  • Invited