Synthesis and application of asterolaurins having anti-cancer activity

• Project/Area Number: 23790018
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: WATANABE Kazuhiro 東北薬科大学, 薬学部, 講師 (10382673)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗がん活性物質 / 抗HIV活性物質 / アステロラウリン類 / キセニカン骨格 / 環拡大反応 / アステロラウリン / トシル化 / ワンポット環化 / コンホマー / 抗がん活性 / 全合成 / 生物活性相関研究

Outline of Final Research Achievements

Synthesis of the xenialactol-methylacetal core and the unsaturated fatty acid side chain of 9-deoxyxenialactol C (asterolaurins analogue) were achieved. The synthetic method involved the following key step: i) [1,3]-sigmatropic rearrangement, ii) isomerization of nitrile and iii) acid-induced domino deprotection/lactol cyclization/methylacetalization in one step.

Research Products

• [Journal Article] Deprotection of 3, 4-Dimethoxybenzyl(^<3, 4> DMB) Group onγ-Lactam Nitrogen Using Phenyliodine(III) Bis(trifluoroacetate)(PIFA): Application to Isoindolinone C ompounds (2012)
  • Author(s): Kazuhiro Watanabe, Hiroaki Shibata, Y. Imai, Tadashi Katoh
  • Journal Title: Heterocycles Volume: 84巻 Issue: 2 Pages: 1355-1361
  • DOI: 10.3987/com-11-s(p)77
  • Peer Reviewed
• [Journal Article] Enantioselective Total Synthesis of(+)-Stachyflin : A Potential Anti-Influenza A Virus Agent Isolated from a Microorganism (2011)
  • Author(s): Ohgi Takahashi, Kazuhiro Watanabe, Tadashi Katoh
  • Journal Title: Eur. J. Org. Chem. Volume: 2011 Issue: 16 Pages: 2948-2957
  • DOI: 10.1002/ejoc.201100173
  • Peer Reviewed
• [Journal Article] Effective Chemoselective Deprotection of 3, 4-Dimethoxybenzyl(^<3, 4> DMB) Ethers in the Presence of Benzyl and p-Methoxybenzyl(PMB) Ethers by Phenyliodine(III) bis(trifluoroacetate)(PIFA) (2011)
  • Author(s): Kazuhiro Watanabe, Tadashi Katoh
  • Journal Title: Tetrahedron Lett. Volume: 52巻 Issue: 41 Pages: 5395-5397
  • DOI: 10.1016/j.tetlet.2011.08.049
  • Peer Reviewed
• [Presentation] 抗がん活性天然物マンデラリドAの全合成に向けて: Ag(I) 触媒による cis-2,5-DHF および 3,6-DHP の合成 (2014)
  • Author(s): 渡邉一弘
  • Organizer: 第１３回化学系若手研究者セミナー（日本薬学会東北支部主催）
  • Place of Presentation: 東北薬科大学（宮城県仙台市）
  • Year and Date: 2014-06-09
  • Invited
• [Presentation] Ag(I)-Catalyzed Cyclization of Propargylic Benzoates to Access Polysubstituted THP Rings (2014)
  • Author(s): Kazuhiro Watanabe, Nagarathanam Veerasamy, Rich G. Cartera
  • Organizer: 247th ACS National Meeting & Exposition
  • Place of Presentation: Dallas, TX, USA
• [Presentation] Synthetic Studies Toward C15-C24 Northern Half of Mandelalide A (2014)
  • Author(s): Nagarathanam Veerasamy, Kazuhiro Watanabe, Rich G. Cartera
  • Organizer: 247th ACS National Meeting & Exposition
  • Place of Presentation: Dallas, TX, USA
• [Presentation] Synthesis of Dihydropyran Derivatives Using Ag(I)-Catalyzed Cyclization: Model Study Towards Southern Half of Mandelalide A (2013)
  • Author(s): Kazuhiro Watanabe, Rich G. Carter
  • Organizer: 68th ACS Northwest Regional Meeting (NORM13)
  • Place of Presentation: Corvallis, OR, USA
• [Presentation] 抗インフルエンザウィルス活性を有するストロンギリン A の全合成 (2013)
  • Author(s): 神島 尭明、渡邉 一弘、加藤 正
  • Organizer: 日本薬学会 第１３３年会
  • Place of Presentation: 横浜
• [Presentation] p21rasファルネシルトランスフェラーゼ阻害物質 TAN-1813 の合成研究 (2012)
  • Author(s): 渡邉一弘、千田一慶、佐藤静香、 成田紘一、加藤 正
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 札幌
• [Presentation] スピルコスタチン C および D の合成と活性評価 (2012)
  • Author(s): 成田紘一、福井友理恵、佐藤静香、 渡邉一弘、加藤 正
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 札幌
• [Presentation] HDAC 阻害剤ブルックホルダックAの全合成 (2012)
  • Author(s): 福井友理恵、成田紘一、佐藤静香、 渡邉一弘、加藤 正
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 札幌
• [Presentation] Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A, B and FK228 (FR901228) (2011)
  • Author(s): Koichi Narita, Kazuhiro Watanabe, Takao Yamoria, Minoru Yoshidab, Tadashi Katoh
  • Organizer: Italian-Japanese International Seminar for Neuroscience
  • Place of Presentation: Sendai, Japan
• [Presentation] Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A, B and FK228 (FR901228) (2011)
  • Author(s): Koichi Narita, Kazuhiro Watanabe, Takao Yamori, Minoru Yoshida, Tadashi Katoh
  • Organizer: AIMECS 11
  • Place of Presentation: Tokyo, Japan
• [Book] 基礎有機化学問題集 (2013)
  • Author(s): 廣田 耕作、西出 喜代治、片岡 貞、渡邉一弘、他
  • Total Pages: 24
  • Publisher: 廣川書店
• [Remarks] 東北薬科大学 医薬合成化学教室
  • URL: http://www.tohoku-pharm.ac.jp/new/index.cgi?eid=109
• [Remarks] 東北薬科大学 医薬合成化学教室 ホームページ
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/iyakugo/index.html
• [Remarks] オレゴン州立大学 Rich G. Carter 研究室ホームページ
  • URL: http://oregonstate.edu/dept/chemistry/carter/
• [Remarks] 東北薬科大学 医薬合成化学研究室ホームページ
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/iyakugo/index.html
• [Remarks] 東北薬科大学 医薬合成化学教室 ホームページ
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/iyakugo/index.html
• [Remarks] オレゴン州立大学 Rich G. Carter 研究室
  • URL: http://chemistry.oregonstate.edu/carter.html
• [Remarks] 東北薬科大学 医薬合成化学教室
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/iyakugo/index.html