Synthetic study of terpenoid for anti-cancer drug and its molecular probe

• Project/Area Number: 17K01952
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Yokohama College of Pharmacy
• Principal Investigator: Shoji Mitsuru 横浜薬科大学, 薬学部, 教授 (30339139)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ジテルペン / 抗腫瘍活性 / 全合成 / コチレニン / テルペン / 配糖体

Outline of Final Research Achievements

Cotylenin A was isolated from unidentified fungus and it is a highly potent anti-cancer drug candidate with low toxicity. The fungus does not produce cotylenin A now and its chemical synthesis is highly desirable. We prepared the three parts of cotylenin A and its supply is now in progress.

Academic Significance and Societal Importance of the Research Achievements

新薬候補化合物として期待されている天然物コチレニンAが化学合成で供給できるようになれば、高い活性を持ちながら副作用の少ない新しい抗がん剤を開発することができる。本研究では、コチレニンAの３つの部位に分割し、それぞれを合成し、全合成達成への道を拓いた。コチレニンAを化学合成できるようになれば、量的供給が可能になり、新薬開発が期待される。

Research Products

• [Journal Article] Chemo-enzymatic Synthesis of (R)-5-Hydroxymethyl-2-isopropyl-5-methylcyclopent-1-en-1-yl Trifluoromethylsulfonate, a Potential Chiral Building Block for Multicyclic Terpenoids (2017)
  • Author(s): Kazuaki Kuwata, Kengo Hanaya, Takeshi Sugai, Mitsuru Shoji
  • Journal Title: Tetrahedron: Asymmetry Volume: 28 Issue: 7 Pages: 964-968
  • DOI: 10.1016/j.tetasy.2017.05.007
  • Peer Reviewed
• [Presentation] Synthesis of Anti-cancer Sesquiterpene via Regio- and Diastereoselective [4 + 3] Cycloaddition (2019)
  • Author(s): Mitsuru Shoji, Shuichi Hagihara, Kengo Hanaya, Takeshi Sugai
  • Organizer: Medicinal Chemistry International Symposium on Advances in Synthetic and Medicinal Chemistry
  • Int'l Joint Research
• [Presentation] Synthesis of Englerin A via Regio- and Diastereoselective [4 + 3] Cycloaddition (2018)
  • Author(s): Mitsuru Shoji
  • Organizer: International Congress on Pure & Applied Chemistry (ICPAC) 2018
  • Int'l Joint Research / Invited
• [Presentation] イソプロピルシクロペンテン誘導体の効率的合成法の開発 (2018)
  • Author(s): 小林瑛宏, 庄司満
  • Organizer: 第62回日本薬学会関東支部大会
• [Presentation] 生合成模倣的フロー合成によるパルミチン酸および Queen bee acid の合成研究 (2018)
  • Author(s): 梅沢 岬, 酒井 佑宜, 吉田 行美, 庄司 満, 高橋 孝志
  • Organizer: 新規素材探索研究会第17回セミナー
• [Presentation] ホスファチジルエタノールアミンの脂肪酸側鎖と抗ピロリ菌化合物の相互作用 (2018)
  • Author(s): 鰐渕清史, 竹澤元貴, 下村裕史, 庄司満, 高橋孝志
  • Organizer: 第62回日本薬学会関東支部大会
• [Remarks] 横浜薬科大学大学院創薬化学領域・創薬研究センター
  • URL: https://kwanibuchi.wixsite.com/mysite/blank-1