Divergent syntheses of lactams and quinone dimers, and evaluation of their phycical and biological properties

• Project/Area Number: 15K07416
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Tokyo University of Science (2016-2017); Kyoto Prefectural University (2015)
• Principal Investigator: Kuramochi Koji 東京理科大学, 理工学部応用生物科学科, 准教授 (90408708)
• Co-Investigator(Kenkyū-buntansha): 水品 善之 信州大学, 学術研究院農学系, 教授 (20307705)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 多様性指向合成 / ラクタム / キノン / 天然物合成 / 生合成 / ナフトキノン / 生合成模倣合成 / 天然物 / 全合成 / 生物活性

Outline of Final Research Achievements

Diversity-oriented synthesis (DOS) aims to generate chemical librarys, which have structural diversity in an efficient manner. Diversity-oriented synthesis is used as a tool for the discovery of biologically and functionally active small molecules. However, DOS requires novel strategies that differ from the majority of traditional chemical syntheses. In this study, we focus on unified and common intermediate strategies for the synthesis lactams and naphthoquinone dimers. Efficient syntheses of lactams and naphthoquinone dimers were developed. Severel natural products and their structurally related analogues were prepared based on the strategies. Functional and biological evaluation of synthetic compounds revealed novel candidate compounds.

Research Products

• [Journal Article] Bioinspired Synthesis of Juglorubin from Juglomycin C (2018)
  • Author(s): Kamo Shogo、Kuramochi Kouji、Tsubaki Kazunori
  • Journal Title: Organic Letters Volume: 20 Issue: 4 Pages: 1082-1085
  • DOI: 10.1021/acs.orglett.7b04051
  • Peer Reviewed
• [Journal Article] Syntheses of Naturally Occurring Lactams by the Use of Darzens Reaction (2018)
  • Author(s): 倉持幸司、小森健太、水谷将馬、椿一典
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 76 Issue: 3 Pages: 218-225
  • DOI: 10.5059/yukigoseikyokaishi.76.218
  • NAID: 130006449127
  • ISSN: 0037-9980, 1883-6526
  • Peer Reviewed
• [Journal Article] Skeletal Rearrangements of Polycyclic α-Ketols (2017)
  • Author(s): Kawamura, M.; Kamo, S.; Azuma, S.; Kubo, K.; Sasamori, T.; Tokitoh, N.; Kuramochi, K.; Tsubaki, K.
  • Journal Title: Org. Lett. Volume: 19 Issue: 2 Pages: 301-303
  • DOI: 10.1021/acs.orglett.6b03541
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Bioinspired Synthesis of (±)-Rubrobramide, (±)-Flavipucine, and Isoflavipucine (2016)
  • Author(s): Mizutani, S., Komori, K., Taniguchi, T., Monde, K., Kuramochi, K., Tsubak, K.
  • Journal Title: Angew. Chem., Int. Ed. Volume: 55 Issue: 33 Pages: 9553-9556
  • DOI: 10.1002/anie.201602910
  • Peer Reviewed
• [Journal Article] Total Syntheses of Juglorescein and Juglocombins A and B (2016)
  • Author(s): Shogo Kamo, Kai Yoshioka, Kouji Kuramochi, Kazunori Tsubaki
  • Journal Title: Angewandte Chemie International Edition Volume: 55 Issue: 35 Pages: 10317-10320
  • DOI: 10.1002/anie.201604765
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The second generation synthesis of (±)-berkeleyamide D. (2016)
  • Author(s): Shoma Mizutani, Kenta Komori, Chiharu Kai, Kouji Kuramochi, Kazunori Tsubaki
  • Journal Title: Tetrahedron Volume: 72 Issue: 42 Pages: 6640-6645
  • DOI: 10.1016/j.tet.2016.08.080
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] One-pot Synthesis of Juglorubin (2018)
  • Author(s): Shogo Kamo, Kouji Kuramochi, Kazunori Tsubaki
  • Organizer: 日本化学会 第98春季年会（2018）
• [Presentation] シクロペンタジエニルアニオンを有する天然色素 Juglorubin の全合成 (2017)
  • Author(s): 加茂翔伍、吉岡快、倉持幸司、椿一典
  • Organizer: 日本農芸化学会 2017 年度大会
  • Place of Presentation: 京都女子大学（京都府京都市）
  • Year and Date: 2017-03-17
• [Presentation] Total Synthesis of Juglorubin, A Natural Red Dye Containing a Cyclopentadienyl Anion (2017)
  • Author(s): Shogo Kamo, Kai Yoshioka, Kouji Kuramochi, Kazunori Tsubaki
  • Organizer: 45th National Organic Chemistry Symposium
  • Int'l Joint Research
• [Presentation] Biomimetic Syntheses of (±)-Rubrobramide, (±)-Flavipucine, Isoflavipucine, and (±)-Berkeleyamide D (2017)
  • Author(s): Kouji Kuramochi, Shoma Mizutani, Kenta Komori, Chiharu Kai, Yasuha Kusakabe, Kazunori Tsubaki
  • Organizer: 45th National Organic Chemistry Symposium
  • Int'l Joint Research
• [Presentation] 合成ラクタム天然物群の生物活性評価 (2017)
  • Author(s): 日下部泰葉、水谷将馬、椿一典、倉持幸司
  • Organizer: 日本農芸化学会関東支部 2017 年度 支部大会
• [Presentation] シクロペンタジエニルアニオンを有する天然赤色色素 Juglorubin の全合成 (2017)
  • Author(s): 加茂翔伍、吉岡快、倉持幸司、椿一典
  • Organizer: 第 59 回 天然有機化合物討論会
• [Presentation] 生合成経路に着想を得た天然物の全合成 (2017)
  • Author(s): 倉持幸司
  • Organizer: 第18回 静岡ライフサイエンスシンポジウム
  • Place of Presentation: 静岡大学（静岡県静岡市）
  • Invited
• [Presentation] 1,4-ナフトキノン天然物群の系統的合成法の開発 (2016)
  • Author(s): 吉岡快、加茂翔伍、真鍋祐梨、倉持幸司、椿一典
  • Organizer: 第 58 回天然有機化合物討論会
  • Place of Presentation: 東北大学（宮城）
  • Year and Date: 2016-09-14
• [Presentation] 1,4-ナフトキノン二量体天然物の全合成研究 (2016)
  • Author(s): 加茂翔伍、吉岡快、倉持幸司、椿一典
  • Organizer: 第14回 次世代を担う有機化学シンポジウム
  • Place of Presentation: 長井記念館（東京都渋谷区）
  • Year and Date: 2016-05-27
• [Presentation] 系統的手法を用いた1,4-ナフトキノン天然物群の合成研究 (2016)
  • Author(s): 吉岡快、加茂翔伍、倉持幸司、椿一典
  • Organizer: 日本農芸化学会関西支部例会 第494回講演会
  • Place of Presentation: 京都府立大学（京都府京都市）
  • Year and Date: 2016-05-21
• [Presentation] Juglocombin A, B 及びJuglorescein の全合成研究 (2016)
  • Author(s): 加茂 翔伍, 吉岡 快, 倉持 幸司, 椿 一典
  • Organizer: 日本薬学会136年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-03-26
• [Presentation] Darzens 反応を利用したラクタム天然物群の全合成 (2015)
  • Author(s): 水谷将馬、谷口 透、小森健太、門出健次、倉持幸司、椿 一典
  • Organizer: 第４５回複素環化学討論会
  • Place of Presentation: 早稲田大学
  • Year and Date: 2015-11-19
• [Presentation] 1,4-ナフトキノン二量化反応の開発とナフトキノンに量体天然物の全合成研究 (2015)
  • Author(s): 加茂翔伍、吉岡快、倉持幸司、椿一典
  • Organizer: 第57回 天然有機化合物討論会
  • Place of Presentation: 横浜・神奈川県民ホール
  • Year and Date: 2015-09-09
• [Presentation] Juglorubin及び関連天然物の全合成研究 (2015)
  • Author(s): 加茂翔伍、倉持幸司、椿一典
  • Organizer: 第489回 日本農芸化学会関西支部例会
  • Place of Presentation: 京都府立大学
  • Year and Date: 2015-05-23