Studies toward development of a novel CTZ-type hydrogen sulfide probe

• Project/Area Number: 26560443
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hosoya Takamitsu 東京医科歯科大学, 生体材料工学研究所, 教授 (60273124)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ケミカルバイオロジー / 有機合成化学 / アジド / ピラジン / セレンテラジン / 化学プローブ / 生物発光 / イメージング / ルシフェリン

Outline of Final Research Achievements

We aimed to develop a new method that is capable of detecting hydrogen sulfide with a novel coelenterazine (CTZ)-type probe. To achieve this purpose, we conducted following studies regarding the synthesis of CTZ-related compounds and reactivities of azide molecules. (1) A novel synthetic method for v-coelenterazine (v-CTZ), which is a vinylene-bridged analog of native CTZ with a large red-shifted luminescence property, has been developed. The synthesis was achieved in a concise way through the use of three sequential cross-coupling reactions and ring-closing metathesis (RCM). (2) We have found that four different substituents can be introduced into pyrazine via four palladium-catalyzed regioselective cross-coupling reactions, using trihalogenated aminopyrazine as the starting material. (3) We have revisited the reduction of azides using a variety of phosphines and achieved a selective reduction of an aromatic azido group under mild conditions.

Research Products

• [Journal Article] Concise Synthesis of v‐Coelenterazines (2015)
  • Author(s): Takamitsu Hosoya, Rie Iimori, Suguru Yoshida, Yuto Sumida, Yuiko Sahara-Miura, Jun-ichi Sato, Satoshi Inouye
  • Journal Title: Organic Letters Volume: 17 Issue: 15 Pages: 3888-3891
  • DOI: 10.1021/acs.orglett.5b01872
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] クロスカップリング反応により４つの置換基を自在に導入可能なピラジン合成法の開発 (2016)
  • Author(s): 秋山 圭、西山義剛、吉田 優、細谷孝充
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学京田辺キャンパス（京都府京田辺市）
  • Year and Date: 2016-03-24
• [Presentation] ４度のクロスカップリング反応を利用した４置換ピラジン合成法の開発 (2015)
  • Author(s): 秋山 圭、西山義剛、吉田 優、細谷孝充
  • Organizer: 第5回CSJ化学フェスタ2015
  • Place of Presentation: タワーホール船堀(東京都江戸川区)
  • Year and Date: 2015-10-13