Synthesis of Novel Nucleoside Derivatives Applicable to Nucleic Acids Medicine

• Project/Area Number: 21590119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: YOSHIMURA Yuichi 東北薬科大学, 薬学部, 准教授 (00230813)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヌクレオシド / 抗HIV活性 / 光延反応 / Pummerer反応 / イソヌクレオシド / 炭素環ヌクレオシド / 閉環メタセシス反応 / 核酸医薬 / ジヒドロチオピラン / グリコシル化

Research Abstract

To develop nucleoside derivatives applicable to nucleic acids medicine with high affinity and stability and to search new anti-HIV agents, we designed and synthesized novel nucleoside derivatives. The target compounds were nucleosides having 2, 6-dioxabicyclo[3.2.0] heptane, dihydropyran and dihydrothiopyran derivatives as pseudosugar moieties. Among the compounds synthesized, dihydrothiopyranylcytosine showed significant anti-HIV activity.

Research Products

• [Journal Article] A New Route to N1-Substituted Uracil Derivatives Using Hypervalent Iodine (2012)
  • Author(s): Yoshimura, Y.; Kan-no, H.; Kiran, Y. B.; Natori, Y.; Saito, Y.; Takahata, H
  • Journal Title: Synthesis Volume: 44 Pages: 1163-1170
• [Journal Article] Synthesis of 5-Thiodidehydropyranylcytosine Derivatives as Potential anti-HIV Agents (2011)
  • Author(s): Yoshimura, Y.; Yamazaki, Y.; Saito, Y.; Natori, Y.; Imamichi, T.; Takahata, H
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 21 Pages: 3313-3316
• [Journal Article] An Access to theβ-Anomer of 4'-Thio-C-ribonucleosides : Hydroboration of 1-C-Aryl-or 1-C-Heteroaryl-4-thiofuranoid Glycals and Its Regiochemical Outcome (2011)
  • Author(s): Haraguchi, K.; Horii, C.; Yoshimura, Y.; Ariga, F.; Tadokoro, A.; Tanaka, H
  • Journal Title: J. Org. Chem Volume: 76 Pages: 8658-8669
• [Journal Article] Synthesis of 5-Thiodidehydropyranylcytosine Derivatives as Potential anti-HIV Agents (2011)
  • Author(s): Yoshimura, Y.; Yamazaki, Y.; Saito, Y.; Natori, Y.; Imamichi, T.; Takahata, H.
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 21 Issue: 11 Pages: 3313-3316
  • DOI: 10.1016/j.bmcl.2011.04.006
  • Peer Reviewed
• [Journal Article] An Access to the β-Anomer of 4'-Thio-C-ribonucleosides : Hydroboration of 1-C-Aryl- or 1-C-Heteroaryl-4-thiofuranoid Glycals and Its Regiochemical Outcome (2011)
  • Author(s): Haraguchi, K.; Horii, C.; Yoshimura, Y.: Ariga, F.; Tadokoro, A.; Tanaka, H.
  • Journal Title: J.Org.Chem. Volume: 76 Issue: 21 Pages: 8658-8669
  • DOI: 10.1021/jo201100n
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Isonucleosides Constructed on a 2-Oxa-6-thiabicyclo[3.2.0] heptane Scaffold (2010)
  • Author(s): Yoshimura, Y.; Asami, K.; Imamichi, T.; Kuroda, T.; Shiraki, K.; Takahata, H
  • Journal Title: J. Org. Chem Volume: 75 Pages: 4161-4171
• [Journal Article] Synthesis and Antiviral Evaluation ofα-D-2', 3'-Did ehydro-2', 3'-dideoxy-3'-C-hydroxymethyl Nucleosides (2010)
  • Author(s): Yamada, K.; Hayakawa, H.; Sakata, S.; Ashida, N.; Yoshimura, Y
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 20 Pages: 6013-6016
• [Journal Article] Design and Synthesis of Isonucleosides Constructed on a 2-Oxa-6-thiabicyclo[3.2.0]heptane Scaffold (2010)
  • Author(s): Yoshimura, Y.; Asami, K.; Imamichi, T.; Kuroda, T.; Shiraki, K.; Takahata, H.
  • Journal Title: J.Org.Chem. Volume: 75 Pages: 4161-4171
  • Peer Reviewed
• [Journal Article] Synthesis and Antiviral Evaluation of α -D-2', 3'-Didehydro-2', 3'-dideoxy-3'-C-hydroxymethyl Nucleosides (2010)
  • Author(s): Yamada, K.; Hayakawa, H.; Sakata, S.; Ashida, N.; Yoshimura, Y.
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 20 Pages: 6013-6016
  • Peer Reviewed
• [Journal Article] グリコシド結合形成反応の開発と新規生物活性ヌクレオシド誘導体合成への展開 (2009)
  • Author(s): 吉村祐一、高畑廣紀
  • Journal Title: 有機合成化学協会詩 Volume: 67 Pages: 798-808
  • NAID: 10025399748
• [Journal Article] Synthesis of 1-(5, 6-Dihydro-2H-thiopyran-2-yl) uracil by a Pummerer-type Thioglycosylation Reaction : The Regioselectivity of Allylic Substitution (2009)
  • Author(s): Yoshimura, Y.; Yamazaki, Y.; Saito, Y.; Takahata, H
  • Journal Title: Tetrahedron Volume: 65 Pages: 9091-9102
• [Journal Article] グリコシド結合形成反応の開発と新規生物活性ヌクレオシド誘導体合成への展開 (2009)
  • Author(s): 吉村祐一、高畑廣紀
  • Journal Title: 有機合成化学協会詩 67 Pages: 798-808
  • NAID: 10025399748
  • Peer Reviewed
• [Journal Article] Synthesis of 1-(5, 6-Dihydro-2H-thiopyran-2-yl) uracil by a Pummerer-type Thioglycosylation Reaction : The Regioselectivity of AHylic Substitution (2009)
  • Author(s): Yuichi Yoshimura, Yoshiko Yamazaki, Yukako Saito, Hiroki Takahata
  • Journal Title: Tetrahedron 65 Pages: 9091-9102
  • Peer Reviewed
• [Presentation] ジヒドロピラノヌクレオシドの合成 (2012)
  • Author(s): 吉村祐一, 尾本瞬, 湊咲絵, 斎藤有香子, 名取良浩, 高畑廣紀
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌(北海道大学)
  • Year and Date: 2012-03-29
• [Presentation] Synthesis of Nucleoside Derivatives using Novel Glycosylation Reaction (2011)
  • Author(s): Yuichi Yoshimura ; Hiroki Takahata
  • Organizer: 6th International Conference on Cutting-Edge Organic Chemistry in Asia(ICCEOCA-6)
  • Place of Presentation: 香港
  • Year and Date: 2011-12-12
• [Presentation] Synthesis of Nucleoside Derivatives using Novel Glycosylation Reaction (2011)
  • Author(s): Yoshimura, Y.; Takahata, H.
  • Organizer: 6th International Conference on Cutting-Edge Organic Chemistry in Asia (ICCEOCA-6)
  • Place of Presentation: 香港(The Chinese University of Hong Kong)
  • Year and Date: 2011-12-12
• [Presentation] Design and Synthesis of 5'-Thio-pyrano-nucleosides as Potential Anti-HIV Agents (2011)
  • Author(s): Yuichi Yoshimura, Yoshiko Yamazaki, Yukako Saito, Yoshihiro Natori, Tomozumi Imamichi, Hiroki Takahata
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium(AIMECS11)
  • Place of Presentation: 東京
  • Year and Date: 2011-12-01
• [Presentation] Design and Synthesis of a Novel Ring-expanded Dihydrothiopyranyl Nucleosides (2011)
  • Author(s): Yoshiko Yamazaki, Yuichi Yoshimura, Yukako Saito, Yoshihiro Natori, Tomozumi Imamichi, Hiroki Takahata
  • Organizer: 15th SIGMA-ALDRICH Organic Synthesis Meeting
  • Place of Presentation: ベルギー
  • Year and Date: 2011-12-01
• [Presentation] Design and Synthesis of 5'-Thio-pyrano-nucleosides as Potential Anti-HIV Ag (2011)
  • Author(s): Yuichi Yoshimura, Yoshiko Yamazaki, Yukako Saito, Yoshihiro Natori, Tomozumi Imamichi, Hiroki Takahata
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: 東京(京王プラザホテル)
  • Year and Date: 2011-12-01
• [Presentation] Design and Synthesis of a Novel Ring-expanded Dihydrothiopyranyl Nucleoside (2011)
  • Author(s): Yoshiko Yamazaki, Yuichi Yoshimura, Yukako Saito, Yoshihiro Natori, Tomozumi Imamichi, Hiroki Takahata
  • Organizer: 15th SIGMA-ALDRICH Organic Synthesis Meeting
  • Place of Presentation: ベルギー(Universite Catolique de Louvain)
  • Year and Date: 2011-12-01
• [Presentation] ジヒドロピラノヌクレオシドの合成 (2011)
  • Author(s): 吉村祐一, 尾本瞬, 湊咲絵, 斎藤有香子, 名取良浩, 高畑廣紀
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2011-03-29
• [Presentation] 2, 6-Dioxabicyclo[3.2.0] heptane骨格を有するイソヌクレオシドのデザインと合成 (2010)
  • Author(s): 吉村祐一, 小林学史, 金子仁美, 鈴木剛, 高畑廣紀
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2010-11-18
• [Presentation] 2, 6-Dioxabicyclo[3.2.0]heptane骨格を有するイソヌクレオシドのデザインと合成 (2010)
  • Author(s): 吉村祐一, 小林学史, 金子仁美, 鈴木剛, 高畑廣紀
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都テルサ(京都)
  • Year and Date: 2010-11-18
• [Presentation] ジヒドロチオピランを疑似糖部とする新規ヌクレオシド誘導体のデザインと合成 (2010)
  • Author(s): 山崎佳子, 吉村祐一, 斎藤有香子, 高畑廣紀
  • Organizer: 第40回複素環化学討論会
  • Place of Presentation: 仙台
  • Year and Date: 2010-10-16
• [Presentation] ジヒドロチオピランを疑似糖部とする新規ヌクレオシド誘導体のデザインと合成 (2010)
  • Author(s): 山崎佳子, 吉村祐一, 斎藤有香子, 高畑廣紀
  • Organizer: 第40回複素環化学討論会
  • Place of Presentation: 仙台市民会館(仙台)
  • Year and Date: 2010-10-16
• [Presentation] 核酸医薬への応用を目指したジヒドロチオピラノヌクレオシドのデザインと合成 (2009)
  • Author(s): 山崎佳子、吉村祐一、高畑廣紀
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-11-26
• [Presentation] 核酸医薬への応用を目指したジヒドロチオピラノヌクレオシドのデザインと合成 (2009)
  • Author(s): 山崎佳子、吉村祐一、高畑廣紀
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2009-11-26
• [Presentation] 超原子価ヨウ素試薬によるアリルシランと核酸塩基のカップリング反応を利用した新規炭素環ヌクレオシド合成法の開発 (2009)
  • Author(s): 吉村祐一、太田匡俊、今堀龍志、高畑廣紀
  • Organizer: 第95回有機合成シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-06-10
• [Presentation] 超原子価ヨウ素試薬によるアリルシランと核酸塩基のカップリング反応を利用した新規炭素環ヌクレオシド合成法の開発 (2009)
  • Author(s): 吉村祐一、太田匡俊、今堀龍志、高畑廣紀
  • Organizer: 第95回有機合成シンポジウム
  • Place of Presentation: 慶應義塾大学薬学部(東京)
  • Year and Date: 2009-06-10
• [Presentation] ラジカル環化を用いた炭素架橋シクロヌクレオシドの合成
  • Author(s): 吉村祐一, 和知克典, 山崎佳子, 高畑廣紀
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] ラジカル環化を用いた炭素架橋シクロヌクレオシドの合成
  • Author(s): 吉村祐一, 和知克典, 山崎佳子, 高畑廣紀
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡(アブストラクトのみ公表 震災により中止)