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Solid-and Solution-Phase Synthesis of Natural Product-Based Libraries

Research Project

Project/Area Number 14103013
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Synthetic chemistry
Research InstitutionTokyo Institute of Technology

Principal Investigator

TAKAHASHI Takashi  Tokyo Institute of Technology, Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, Professor, 大学院理工学研究科, 教授 (80110724)

Co-Investigator(Kenkyū-buntansha) DOI Takayuki  Tokyo Institute of Technology, Department of Applied Chemistry, Graduate School of Science and Engineering, Associate Professor, 大学院理工学研究科, 助教授 (90212076)
TANAKA Hiroshi  Tokyo Institute of Technology, Department of Applied Chemistry, Graduate School of Science and Engineering, Assistant Professor, 大学院理工学研究科, 助手 (40334544)
Project Period (FY) 2002 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥100,620,000 (Direct Cost: ¥77,400,000、Indirect Cost: ¥23,220,000)
Fiscal Year 2006: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2005: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2004: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2003: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2002: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
KeywordsCombinatorial Chemistry / Natural Products / Chemical Probes / Compound Libraries / Solid-Phase Synthesis / One-Pot Glycosylation / Cyclic Compounds / アミド結合 / 異常アミノ酸 / コンビトリアルケミストリー / 固相合成法 / プロスタノイド / パラジウム反応 / アルドール反応 / ライブラリー / 天然有機化合物 / 糖アミノ酸 / コア2 / ワンポットグリコシル化反応 / フッ化糖 / シリルエーテル / クラボロン / パラジウム / オリゴ糖 / 並列合成装置 / ファイトアレキシンエリシター / 自動合成
Research Abstract

Biologically active natural products have served as effective biochemical probes for discovery of not only new drug targets but also new biomarkers. The synthesis of small molecules based upon the structure of biologically active natural products would be an effective and promising way for identification of new biochemical probes. Combinatorial chemistry can assist the high-speed synthesis of these focused liberties. The combinatorial approach might not be an economic route in comparison with the traditional approach based on elucidating the best fragment at each diverse site because fully combinatorial liberties contain many redundant compounds. However, in traditional approach the compounds composed of the best fragments would not often exhibit the strongest biological activity in cell-based assay since cell-permeability of the small molecules would largely influence their biological activity. In this research project, we investigated the development of effective approaches for the solid- and solution-phase synthesis of natural product-based libraries.
Research for the solid-phase synthesis of natural product-based libraries resulted in the syntheses of 25 aurilide derivatives, 122 macrosphelide A derivatives, 74 clavulone derivatives, 24 aeruginosin derivatives. In addition, bidirectional solid-phase semisynthesis of vancomycin derivatives was accomplished based on donor-bound glycosylation strategy. On the other hand, for the solution-phase synthesis of natural product-based libraries, we investigated one-pot sequential glycosylation approaches, that are effective not only for high speed synthesis of target oligosaccharides but also for the synthesis of combinatorial libraries. As the results, we succeeded in the development of one-pot glycosylation for the synthesis of a heptasaccharide exhibiting phytoalexin elicitor activity, core 2 type glycosyl amino acids and sialo-containing glycosyl amino acids.

Report

(6 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (36 results)

All 2007 2006 2005 2004 2003 Other

All Journal Article (22 results) Publications (14 results)

  • [Journal Article] Donor-bound Glycosylation for Various Glycosyl Acceptors : Bidirectional Solid-phase Semisynthesis of Vancomycin and Its Derivatives.2007

    • Author(s)
      Takayuki Doi
    • Journal Title

      Chem. Asian J. 2(1)

      Pages: 188-198

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Donor-bound Glycosylation for Various Glycosyl Acceptors : Bidirectional Solid-phase Semisynthesis of Vancomycin and Its Derivatives.2007

    • Author(s)
      Takayuki Doi, Atsushi Kinbara, Hitoshi Inoue, Takashi Takahashi
    • Journal Title

      Chem.Asian J. 1

      Pages: 188-198

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Solid-Phase Synthesis and Biological Activity a Combinatorial Cross-Conjugated Dienone Library.2006

    • Author(s)
      Makoto Kitade
    • Journal Title

      Chem. Eur. J. 12

      Pages: 1368-1376

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Solid-phase Combinatorial Synthesis of Aeruginosin Derivatives and Their Biological Evaluation.2006

    • Author(s)
      Takayuki Doi
    • Journal Title

      J. Comb. Chem. 8

      Pages: 571-582

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Solid-Phase Synthesis and Biological Activity a Combinatorial Cross-Conjugated Dienone Library.2006

    • Author(s)
      Makoto Kitade, Hiroshi Tanaka, Sho Oe, Makoto Iwashima, Kazuo Iguchi, Takashi Takahashi
    • Journal Title

      Chem.Eur.J. 12

      Pages: 1368-1376

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Solid-phase Combinatorial Synthesis of Aeruginosin Derivatives and Their Biological Evaluation.2006

    • Author(s)
      Takayuki Doi, Yoichiro Hoshina, Hiroyuki Mogi, Yoshifumi Yamada, Takashi Takahashi
    • Journal Title

      J.Comb.Chem. 8

      Pages: 571-582

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthetic Study of a(2,8) Oligosialosides using N-Troc sialyl N-Phenyltrifluoroimidate2006

    • Author(s)
      Hiroshi Tanaka
    • Journal Title

      Heterocycles 67

      Pages: 107-112

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A Total Synthesis of Apratoxin A.2006

    • Author(s)
      Takayuki Doi
    • Journal Title

      Org.Lett. 8(3)

      Pages: 531-534

    • NAID

      10021906534

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Solid-Phase Synthesis and Biological Activity a Combinatorial Cross-Conjugated Dienone Library.2006

    • Author(s)
      Makoto Kitade
    • Journal Title

      Chem.Eur.J. 12

      Pages: 1368-1376

    • Related Report
      2005 Annual Research Report
  • [Journal Article] One-Pot Synthesis of Sialo-Containing Glycosyl Amino Acids Using N-Troc β -Thiophenyl Sialoside.2005

    • Author(s)
      Hiroshi Tanaka
    • Journal Title

      Chem. Eur. J. 11

      Pages: 849-862

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] One-Pot Synthesis of Sialo-Containing Glycosyl Amino Acids Using N-Troc β-Thiophenyl Sialoside.2005

    • Author(s)
      Hiroshi Tanaka, Masaatsu Adachi, Takashi Takahashi
    • Journal Title

      Chem.Eur.J.

      Pages: 849-862

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] One-Pot Synthesis of Sialo-Containing Glycosyl Amino Acids Using N-Troc β-Thiophenyl Sialoside.2005

    • Author(s)
      Hiroshi Tanaka
    • Journal Title

      Chem.Eur.J. 11

      Pages: 849-862

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Efficient Stereoselective Synthesis of γ-N-Glycosyl Asparagines by N-Glycosylation of Primary Amide Groups2005

    • Author(s)
      Hiroshi TANAKA
    • Journal Title

      J.Am.Chem.Soc. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An Effective Sialylation Method Using N-Troc- and N-Fmoc-protected β-Thiophenyl Sialosides and Application to the One-pot Two-step Synthesis of 2,6-Sialyl-T Antigen2004

    • Author(s)
      Masaatsu ADACHI
    • Journal Title

      Synlett 4

      Pages: 609-614

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Efficient synthesis of core 2 class glycosyl amino acids by one-pot glycosylation approach2004

    • Author(s)
      Hiroshi TANAKA
    • Journal Title

      Tetrahedron Lett. 45

      Pages: 1433-1436

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Combinatorial synthesis of carbohydrate cluster on tree-type linker with orthogonally cleavable parts2004

    • Author(s)
      Toru AMAYA
    • Journal Title

      Synlett 3

      Pages: 497-502

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Efficient Solid-Phase Synthesis of Clavulones via Sequential Coupling of α- and ω-Chains2004

    • Author(s)
      Hiroshi TANAKA
    • Journal Title

      Org.Lett. 6

      Pages: 1103-1106

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effective Irreversible Alkylating Reagents Based on the Structure of Clavulones2004

    • Author(s)
      Hiroshi TANAKA
    • Journal Title

      Bioorg.Med.Chem.Lett. 14

      Pages: 837-840

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Combinatorial Synthesis of a Macrosphelide Library Utilizing a Palladium-Catalyzed Carbonylation on a Polymer Support.2003

    • Author(s)
      Takashi Takahashi
    • Journal Title

      Angew. Chem. Int. 42

      Pages: 5230-5234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Solid Phase Library Synthesis of Cyclic Depsipeptides : Aurilide and Aurilide Analogues.2003

    • Author(s)
      Takashi Takahashi
    • Journal Title

      J. Comb. Chem. 5

      Pages: 414-428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A Combinatorial Synthesis of a Macrosphelide Library Utilizing a Palladium-Catalyzed Carbonylation on a Polymer Support.2003

    • Author(s)
      Takashi Takahashi, Shin-ichi Kusaka, Takayuki Doi, Toshiaki Sunazuka, Satoshi Omura
    • Journal Title

      Angew.Chem.Int. 42

      Pages: 5230-5234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Solid Phase Library Synthesis of Cyclic Depsipeptides : Aurilide and Aurilide Analogues.2003

    • Author(s)
      Takashi Takahashi, Hiroyuki Nagamiya, Takayuki Doi, Peter G.Griffiths, Andrew M.Bray
    • Journal Title

      J.Comb.Chem. 5

      Pages: 414-428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Publications] Hiroshi Tanaka: "Parallel Synthesis of Multi-branched Oligosaccharides Related to Elicitor Active Pentasaccharide in Rice Cell Based on Orthogonal Deprotection and Glycosylation Strategy"Tetrahedron Lett.. 44. 3053-3057 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Toru Amaya: "Synthesis of 2,3,6-Trideoxysugar Containing Disaccharides by Cyclization and Glycosidation through the Sequential Activation of Sulfoxide and Methylsulfanyl Groups in a One-pot Procedure"Angew.Chem.Int.Ed.Engl.. 42. 1833-1836 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroshi Tanaka: "Efficient Solid-Phase Synthesis of Clavulones via Sequential Coupling of α-and ω-Chains"Org.Lett.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaatsu Adachi: "Effective sialylation method using N-Troc and N-Fmoc β-phenyl thiosialosides and an application to the one-pot two-step synthesis of 2,6-STF Antigen"Synlett.. 609-614 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroshi Tanaka: "Efficient synthesis of core 2 class glycosyl amino acids by one-pot glycosylation approach"Tetrahedron Lett.. 45. 1433-1436 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroshi Tanaka: "Effective Irreversible Alkylating Reagents Based on the Structure of Clavulones"Bioorg.Med.Chem.Lett.. 14. 837-840 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 高橋 孝志: "先端化学シリーズV IIIコンビナトリアル科学「固相合成を用いたコンビナトリアルライブラリーの構築」"丸善(株). 5 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shigeru Miyamoto: "Synthesis of the ABC Ring System of Paclitaxel : Formation of the 8-Membered Ring by Intermolecular Alkylation"Synlett. 1. 97-99 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayuki Doi: "Synthesis of a Tetrabenzyl-substituted 10-Membered Cyclic Diamide"Tetrahedron. 58. 2957-2963 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashi Takahashi: "Solid-Phase Synthesis of a Phytoalexin Elicitor-Active Tetraglucosyl Glucitol"Synlett. 6. 911-914 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroshi Tanaka: "Synthesis of Di-branched Heptasaccharide by One-Pot Glycosylation Using Seven Independent Building Blocks"Org. Lett. 4・24. 4213-4216 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋 孝志: "シリルリンカーを用いた糖ハイブリッド9員環エンジインライブラリーの固相合成法に関する研究"有合化. 60・5. 490-491 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nobuhiro Fuchi: "The Solid-Phase parallel Synthesis of β-Strand mimetic Template via 1,3-dipolar Cyclization with Resin-bound Vinylsulfone"Synlett. 2. 285-289 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋 孝志: "コンビナトリアルサイエンスの新展開「固相合成法の開発と機能性分子ライブラリーの構築:糖一エンジインハイブリッド化合物のライブラリー構築法の開発」"シーエムシー出版. 13 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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