Generation and optimization of macrocyclic synthetic ligands through biomacromolecule-templated cyclizations

• Project/Area Number: 24651253
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Chemical biology
• Research Institution: Hokkaido University
• Principal Investigator: OGURI Hiroki 北海道大学, 理学(系)研究科(研究院), 准教授 (80311546)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: テンプレート合成 / スキャフォールド / マクロ環化 / 多官能性分子 / フラグメント / 多様性指向有機合成 / 多官能性スキャフォールド / ユニット連結 / 触媒的二量化 / 逐次環化 / FBDD / 天然物 / ユニット集積化 / 機能性低分子

Research Abstract

This research intends to develop template-synthesis protocols for generating macrocyclic ligands as specific modulators of targeted biomacro-molecules. In this project, we have designed and synthesized densely functionalized scaffolds capable of integrating multiple functional units on the rigid skeletons. We are exploring assembly peptidyl fragments on the scaffold and subsequent macrocyclization in the presence of biomacromolecule as a template.

Research Products

• [Journal Article] A nickel-catalyzed dimerization of pyrrolidinoindoline scaffold : a systematic access to chimonanthines, folicanchines and (+)-WIN 64821 (2014)
  • Author(s): Mitsuhiro Wada, Takahisa Murata, Hideaki Oikawa, Hiroki Oguri
  • Journal Title: Org. Biomol. Chem Volume: 12 Pages: 298-306
  • Peer Reviewed
• [Journal Article] Sequential [6+2], [2+2], [3+2] Annulations for Rapid Assembly of Multiple Fragments (2013)
  • Author(s): Verisoju Mahendar, Hideaki Oikawa, Hiroki Oguri
  • Journal Title: Chem. Commun Volume: 49 Pages: 2299-2301
  • Peer Reviewed
• [Journal Article] Sequential [6+2], [2+2], and [3+2] annulations for rapid assembly of multiple fragments (2013)
  • Author(s): Velisoju Mahendar, Hideaki Oikawa and Hiroki Oguri
  • Journal Title: Chemical Communications Volume: 49 Issue: 23 Pages: 2299-2301
  • DOI: 10.1039/c2cc38854e
  • Peer Reviewed
• [Journal Article] Hg(OTf)2-Catalyzed Direct Vinylation of Tryptamines and Versatile Applications for Tandem Reactions (2012)
  • Author(s): Haruki Mizoguchi, Hideaki Oikawa, Hiroki Oguri
  • Journal Title: Org. Biomol. Chem Volume: 10 Issue: 2 Pages: 4236-4242
  • DOI: 10.1039/c3ob41918e
  • Peer Reviewed
• [Presentation] 多環性天然物の骨格多様化合成による生理活性化合物群の創製 (2014)
  • Author(s): 大栗博毅
  • Organizer: 日本化学会平成25年度函館地区化学講演会
  • Place of Presentation: 北海道大学函館キャンパス,函館
  • Year and Date: 2014-02-27
• [Presentation] 天然物の骨格多様化合成プロセス開発 (2014)
  • Author(s): 大栗博毅
  • Organizer: 第16回生命化学研究会
  • Place of Presentation: KKRホテル熱海,静岡
  • Year and Date: 2014-01-10
• [Presentation] 逐次的環構築によるフラグメント集積法の開発 (2013)
  • Author(s): 大栗博毅, Velisoju Mahendar,上田拓真,及川英秋
  • Organizer: 日本ケミカルバイオロジー学会第8回年会
  • Place of Presentation: 東京医科歯科大学M&Dタワー鈴木章夫記念講堂, 東京
  • Year and Date: 2013-06-19
• [Presentation] ニッケル触媒によるビスピロリジノインドリン近接四級炭素の構築 (2013)
  • Author(s): 和田光弘,大栗博毅,及川英秋
  • Organizer: 第93日本化学会春季年会
  • Place of Presentation: 立命館大学びわこ・くさつキャンパス,滋賀
  • Year and Date: 2013-03-25
• [Presentation] Design & Expedition Synthesis of Natural Product-Inspired Multi-cyclic Scaffolds : Strategies for Fragment Assembly and Skeletal Diversification (2013)
  • Author(s): 大栗博毅
  • Organizer: 第93日本化学会春季年会有機化学ディビジョンアジア国際シンポジウム
  • Place of Presentation: 立命館大学びわこ・くさつキャンパス,滋賀
  • Year and Date: 2013-03-24
• [Presentation] Chemical Evolution of Natural Products through Generation of Skeletal Variations (2013)
  • Author(s): 大栗博毅
  • Organizer: Asian Chemical Biology Initiative 2013 Bangkok Meeting
  • Place of Presentation: Pullman Bangkok Hotel, Thailan
  • Year and Date: 2013-01-27
• [Presentation] 逐次的環構築によるフラグメント集積法の開発 (2013)
  • Author(s): ○大栗博毅、Velisoju Mahendar、上田拓真、及川英秋
  • Organizer: 日本ケミカルバイオロジー学会
  • Place of Presentation: 東京医科歯科大学、お茶の水、東京
• [Presentation] 逐次的環構築によるフラグメント集積法の開発 (2013)
  • Author(s): 大栗博毅、Velisoju Mahendar、上田拓真、及川英秋
  • Organizer: 日本ケミカルバオロジー学会第8回年会
  • Place of Presentation: 東京（東京医科歯科大学）
• [Presentation] 3D-Fragment Assemblies on Natural Product-Inspired Scaffolds (2012)
  • Author(s): 大栗博毅
  • Organizer: Queenstown Molecular Biology Meetings 2012 : Chemical Biology and Drug Discovery
  • Place of Presentation: Queenstown, New Zealand
  • Year and Date: 2012-08-27
• [Remarks]
  • URL: http://wwwchem.sci.hokudai.ac.jp/~yuhan/member/oguri_public.html
• [Remarks] 報道,ハイライト記事等 : Chem. Commun. 2013, 49, 2299. (雑誌論文②)のハイライト記事掲載:David Bradley"Ten Stereocenters in Five Steps"Chemistry views, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2013年1月11日
  • URL: http://www.chemistryviews.org/details/news/4224191/Ten_Stereocenters_in_Five_Steps.html
• [Remarks] 大栗博毅 研究論文リスト
  • URL: http://wwwchem.sci.hokudai.ac.jp/~yuhan/member/oguri_public.html
• [Remarks] 北海道大学大学院理学研究院化学部門有機反応論研究室
  • URL: http://barato.sci.hokudai.ac.jp/~yuhan/member/index.html