Synthetic study of habiterpenol

• Project/Area Number: 26460013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Kitasato University
• Principal Investigator: Nagamitsu Tohru 北里大学, 薬学部, 教授 (90300756)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 全合成 / 構造活性相関 / 創薬研究 / 合成化学 / 創薬化学

Outline of Final Research Achievements

Habiterpenol (1) was isolated from the fermentation broth of actinomycete Phytohabitans suffuscus 3787_5. Habiterpenol was found to abrogate bleomycin-induced G2 arrest in Jurkat cells. Due to its intriguing structural features and biological profile, total synthesis and structure-activity relationship study of this natural product were investigated. As a result, we successfully synthesized a key intermediate for the total synthesis.

Research Products

• [Journal Article] In vitro metabolism of pyripyropene A and ACAT inhibitory activity of its metabolites. (2015)
  • Author(s): Ohshiro, T.; Matsuda, D.; Ohtawa, M.; Yamazaki, H.; Nagamitsu. T.; Tomoda, H.
  • Journal Title: J. Antibiot. 2015, 25, 313-316. Volume: 68 Issue: 1 Pages: 27-34
  • DOI: 10.1038/ja.2014.91
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and biological activity of 5-(4-methoxyphenyl)-oxazole derivatives (2015)
  • Author(s): D. Yamamuro, R. Uchida, M. Ohtawa, S. Arima, Y. Futamura, M. Katane, H. Homma, T. Nagamitsu, H. Osada, H. Tomoda
  • Journal Title: Bioorg. Medic. Chem. Lett. Volume: 25 Issue: 2 Pages: 313-316
  • DOI: 10.1016/j.bmcl.2014.11.042
  • Peer Reviewed / Open Access
• [Journal Article] Novel Terpenes Generated by Heterologous Expression of Bacterial Terpene Synthase Genes in an Engineered Streptomyces Host (2015)
  • Author(s): Yuuki Yamada, Shiho Arima, Tohru Nagamitsu, Kohei Johmoto, Hidehiro Uekusa, Tadashi Eguchi, Kazuo Shin-ya, David E. Cane, Haruo Ikeda
  • Journal Title: J. Antibiot. Volume: 68 Issue: 6 Pages: 385-394
  • DOI: 10.1038/ja.2014.171
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Design, synthesis and biological evaluation of air-stable nafuredin-γ analogs as complex II inhibitors. (2015)
  • Author(s): Ohtawa, M.; Matsunaga, M.; Fukunaga, K.; Shimizu, R.; Shimizu, E.; Arima, S.; Ohmori, J.; Kita, K.; Shiomi, K.; Omura, S.; Nagamitsu. T.
  • Journal Title: Bioorg. Med. Chem. Volume: 23 Issue: 5 Pages: 932-943
  • DOI: 10.1016/j.bmc.2015.01.030
  • Peer Reviewed / Open Access
• [Journal Article] Total synthesis of (+)-clavulatriene A (2015)
  • Author(s): F. Ito, Y. Ohbatake, S. Aoyama, T. Ikeda, S. Arima, Y. Yamada, H. Ikeda, T. Nagamitsu
  • Journal Title: Synthesis Volume: 47 Issue: 09 Pages: 1348-1355
  • DOI: 10.1055/s-0034-1379898
  • Peer Reviewed / Open Access
• [Presentation] 新規G2 checkpoint阻害物質habiterpenolの合成研究 (2016)
  • Author(s): 下山健太、長光 亨
  • Organizer: 第37回白金シンポジウム
  • Place of Presentation: 北里大学薬学部
  • Year and Date: 2016-12-20
• [Presentation] 新規G2 checkpoint阻害物質habiterpenolの合成研究 (2016)
  • Author(s): 下山健太、内田龍児、供田 洋、長光 亨
  • Organizer: 第42回反応と合成の進歩シンポジウム
  • Place of Presentation: 静岡市清水文化会館マリナート
  • Year and Date: 2016-11-07
• [Presentation] Hydropyrenolおよびhydropyreneneの合成研究 (2016)
  • Author(s): 大畠由伎, 小松千紘, 池田治生, 長光 亨
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-29
• [Presentation] Synthesis and biological activity of citridone A and analogs (2015)
  • Author(s): Shimoyama K, Fukuda T, Tomoda H, Nagamitsu, T
  • Organizer: Pacifichem 2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] Structure-activity relationship study and total synthesis of pyripyropene A as a ACAT2-selective inhibitor (2015)
  • Author(s): Ohtawa M, Ohshiro T, Omura S, Tomoda H, Nagamitsu, T
  • Organizer: Pacifichem 2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] Structure-activity relationship study and total synthesis of pyripyropene A as a ACAT2-selective inhibitor (2015)
  • Author(s): Ohtawa, M.; Ohshiro, T.; Omura, S.; Tomoda. H.; Nagamitsu, T.
  • Organizer: The 13th International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: 京都
  • Year and Date: 2015-11-12
  • Int'l Joint Research
• [Presentation] Cyslabdanの全合成 (2015)
  • Author(s): 大多和 正樹, 菱沼 祐介, 供田 洋, 長光 亨
  • Organizer: 第41回反応と合成の進歩シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-26
• [Remarks] 北里大学薬学部薬品製造化学研究室
  • URL: https://www.pharm-kitasato-u-orgsyn.com