Regioselective Pummerer reacton of 4'-thionucleoside S-oxide : Synthesis of 1'-or 4'-substituted 4'-thionucleoside and its biological activity

• Project/Area Number: 19590106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Showa University
• Principal Investigator: HARAGUCHI Kazuhiro) Showa University, 薬学部, 准教授 (10218638)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヌクレオシド / チオ糖 / Pummerer転位反応 / 抗ウイルス活性 / グリカール / Pummerer転位 / 有機シリコン試剤 / 有機アルミニウム試剤 / 求核置換反応

Research Abstract

4'-チオヌクレオシドS-オキシドの位置選択的なPummerer 反応を基盤とすることにより、1'位あるいは4'位にアセトキシ基を有するヌクレオシド誘導体を合成した。アセトキシ体はルイス酸の存在下、有機シリコン試剤を反応させることにより、1'位あるいは4' 位に炭素鎖の分岐した新規誘導体へ変換することに成功した。

Research Products

• [Journal Article] Synthesis of 4'-Benzoyloxycorycepin from Adenosine (2008)
  • Author(s): Kubota, Y. ; Kunikata, M. ; Ishizaki, N. ; Haraguchi, K. ; Odanaka, Y. ; Tanaka, H.
  • Journal Title: Tetrahedron 64 Pages: 2391-2396
• [Journal Article] Synthesis and Anti-HIV Activity of 4'-Substituted 4'-thiothymidines : A New Entry Based on Nucleophilic Substitution of the 4'-Acetoxy Group (2008)
  • Author(s): Haraguchi, K. ; Shimada, H. ; Tanaka, H. ; Hamasaki, T. ; Baba, M. ; Gullen, E. A. ; Dutschman, G. E. ; Cheng, Y.-C.
  • Journal Title: J. Med. Chem. 51 Pages: 1835-1893
• [Journal Article] Synthesis and Antiviral Evaluation of (±)-4'-Ethynyl-5'-difluoro-carbocyclic-d4T analogue (2008)
  • Author(s): Kumamoto, H. ; Haraguchi, K. ; Ida, M. ; Tanaka, H. ; Hamasaki, T. ; Baba, M.
  • Journal Title: Nucleic acids Symposium Series 52 Pages: 609-610
• [Journal Article] Efficient Removal of Formaraidopyrimidines by 8-Oxoguanine Glycosylases (2008)
  • Author(s): Haraguchi, K., et al.
  • Journal Title: Biochemistry 47 Pages: 1043-1050
  • Peer Reviewed
• [Journal Article] Synthesis of 4'-Benzoyloxycordycepin from Adenosine (2008)
  • Author(s): Haraguchi, K., et. al
  • Journal Title: Tetrahedron 64 Pages: 2391-2396
  • Peer Reviewed
• [Journal Article] Synthesis and Anti-HIV Activity of 4'-Substituted 4'-thiothymidines (2008)
  • Author(s): Haraguchi, K., et. al
  • Journal Title: J. Med. Chem. 51 Pages: 1835-1893
  • Peer Reviewed
• [Journal Article] An Alternative Synthetic Method for 4'-C-Ethynylstavudine by Means of Nucleophilic Substitution of 4'-Benzoyloxythymone Nucleoside (2007)
  • Author(s): Haraguchi, K. ; Sumino, M. ; Tanaka, H.
  • Journal Title: Nucleosides, Nucleotides and Nucleic Acids 26 Pages: 835-839
• [Journal Article] Synthetic Use of Epoxy-sugar Nucleosides (2007)
  • Author(s): Tanaka, H. ; Kubota, Y. ; Takeda, S. ; Haraguchi, K.
  • Journal Title: Nucleosides, Nucleotides and Nucleic Acids 26 Pages: 547-554
• [Journal Article] Additive Pummerer Reaction of 3,5-O-(di-t-butylsilylene)-4- thiofuranoid glycal and Stereoselective Synthesis of β-Anomer of 4'-Thioribonucleosides (2007)
  • Author(s): Haraguchi, K. ; Matsui, H. ; Takami, S. ; Tanaka, H.
  • Journal Title: Nucleic Acids Research Symposium 51 Pages: 143-144
• [Journal Article] Efficient Removal of Formamidopyrimidines by 8-Oxoguanine Glycosylases (2007)
  • Author(s): Krishnamurthy, N. ; Haraguchi, K. ; Greenberg, M. M. ; David, S. S.
  • Journal Title: Biochemistry 47 Pages: 1043-1050
• [Journal Article] Additive Pummerer Reaction of 3,5-0-(Di-t-butylsilylene)-4-thiofuranoid glycal and Stereoselective Synthesis of β-Anomer of 4'-Thioribonucleosides (2007)
  • Author(s): Kazuhiro Haraguchi
  • Journal Title: Nucleic Acids Symposium Series 51 Pages: 143-144
  • Peer Reviewed
• [Journal Article] An Alternative Synthetic Method for 4'-C-Ethynylstavudine by Means of Nucleophilic Substitution of 4-Benzoyloxythymine Nucleoside (2007)
  • Author(s): Kazuhiro Haraguchi
  • Journal Title: Nucleosides, Nucleotides and Nucleic Acids 26 Pages: 835-839
  • Peer Reviewed
• [Journal Article] Synthetic Use of Epoxy-sugar Nucleosides (2007)
  • Author(s): Kazuhiro Haraguchi
  • Journal Title: Nucleosides, Nucleotides and Nucleic Acids 26 Pages: 547-554
  • Peer Reviewed
• [Presentation] Synthesis and Antiviral Evaluation of (±)-4'-Ethynyl-5'-difluoro-carbocyclic D4T analogues (2008)
  • Author(s): 原口 一広
  • Organizer: 第6回国際核酸化学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-09-08
• [Presentation] Synthesis and Anti-HIV Activity of 4'-Substituted 4'-thiothymidines (2008)
  • Author(s): 原口 一広
  • Organizer: International Symposium on Medicinal Chemistry
  • Place of Presentation: オーストリア
  • Year and Date: 2008-08-31
• [Presentation] 4'位にシアノ基およびエチニル基を有する4'-チオチミジンの合成とその抗HIV活性 (2008)
  • Author(s): 原口 一広
  • Organizer: 第18回抗ウイルス療法研究会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-05-24
• [Presentation] トリメチルアルミニウムを用いる4'-ベンゾイルオキシコルジセピンの求核置換反応 (2008)
  • Author(s): 窪田豊、國方真由美、石崎伸英、大石亜佑美、原口一広、田中博道
  • Organizer: 日本薬学会 第128年会
• [Presentation] Synthesis and antiviral evaluation of (±)-4'-ethnyl-5'-difluoro-carbocyclic-D4T analogue (2008)
  • Author(s): H. Kumamoto, K. Haraguchi, M. Ida, H. Tanaka, T. Hamasaki and M. Baba
  • Organizer: 第35回核酸化学シンポジウム(第6回国際核酸化学シンポジウム)
  • Place of Presentation: 京都
• [Presentation] 4'位にシアノ基およびエチニル基を有する4'-チオチミジンの合成とその抗HIV活性 (2008)
  • Author(s): 原口一広、島田央、田中博道、濱崎隆之、馬場昌範、Elizabeth A. Gullen、Ginger E. Dutschman、Yung-Chi Cheng
  • Organizer: 第18回抗ウイルス化学療法研究会
  • Place of Presentation: 鹿児島
• [Presentation] Synthesis and anti-HIV activity of 4'-substituted 4'-thiothymidines: a new entry based on nucleophilic substitution of 4'-acetoxy Group (2008)
  • Author(s): K. Haraguchi, H. Shimada, H. Tanaka, T. Hamasaki, M. Baba, E. A. Gullen, G. E. Dutschman, and Y.-C. Cheng
  • Organizer: International Symposium on Medicinal Chemistry (ISMC07)
  • Place of Presentation: Vienna, Austria
• [Presentation] Nucleophilic Substitution of 4'-Acetoxy-4'-thionucleosides:A New Access to 4'-Substituted 4'-thiothymidines (2007)
  • Author(s): Kazuhiro Haraguchi
  • Organizer: International Symposium on Advances in Synthetic and Medicinal Cheuistry
  • Place of Presentation: St.Petersburg,Russia
  • Year and Date: 2007-08-28
• [Presentation] 4'-チオフラノイドグリカールを利用する4'-チオ-C-ヌクレオシドの合成研究 (2007)
  • Author(s): 原口一広、堀井周文、吉村祐一、有賀史子、田所綾、田中博道
  • Organizer: 日本薬学会 第127年会
• [Presentation] 2'位にアジド基ならびにメトキシ基を有する2'-デオキシ-4'-チオリボヌクレオシドの合成とその抗HCV活性 (2007)
  • Author(s): 原口一広、屋敷千穂、島田央、田中博道、S. K. Jang
  • Organizer: 第17回抗ウイルス化学療法研究会
  • Place of Presentation: 徳島
• [Presentation] Nucleophilic Substitution of 4'-Acetoxy-4'-thionucleosides: a new access to 4'-substituted 4'-thiothymidines (2007)
  • Author(s): K. Haraguchi, H. Shimada, H. Tanaka
  • Organizer: International Symposium on Advances in Synthetic and Medicinal Chemistry (ASMC07)
  • Place of Presentation: St. Pertersburg, Rissia