Synthesis and structure-activity relationship of catechin derivatives having DNA polymerase inhibitory activity

• Project/Area Number: 20590106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Toyama Prefectural University
• Principal Investigator: NAKAJIMA Noriyuki Toyama Prefectural University, 工学部, 教授 (40188959)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: カテキン類 / プロシアニジン類 / 3-アシルカテキン / 3-アシルエピカテキン / γ-butyrolactone / 3-アルキルカテキン / 代謝物 / 比旋光度 / TBS保護基

Research Abstract

3-Acylcatechins and 3-acylepicatechins having TBS-protecting group were chemically synthesized and their DNA polymerase inhibitory activity and the structure-activity relationship was studied. We also developed a simple and versatile method of synthesizing procyanidin oligomers. This method is applicable to the synthesis of [4-8]-condensed (-)-epicatechin series procyanidin tetramers and pentamers. Catechin and epi-catechin conjugated with longer fatty acid (acyl-catechin) strongly inhibited DNA polymerase activity. Procyanidin tetramers and pentamers also inhibited the DNA polymerase much higher than monomeric and dimmeric oligomers. Catechins and epicatechins afford many metabolites including through metabolic pathways in the human body. We interested in the activity of catechin metabolites and synthesized these g-butyrolactones metabolites as the optically pure authentic standards. The study of DNA polymerase inhibitory activity of g-butyrolactones is on going project.

Research Products

• [Journal Article] Role of fatty acid chain length on the induction of apoptosis by newly synthesized catechin derivatives (2010)
  • Author(s): Ahmed, K.; Wei, Z.-L.; Nakajima, N.; Matsunaga T.; Ogasawara, M.; Kondo, T.
  • Journal Title: Chemico-Biological Interactions 185 Pages: 182-188
  • Peer Reviewed
• [Journal Article] Synthesis of Optically Pure Lactone-Metabolites Derived from Tea Catechins (2010)
  • Author(s): Hamada, M.; Furuno, A.; Nakano, S.; Kishimoto, T.; Nakajima, N.
  • Journal Title: Synthesis Pages: 1512-1520
  • Peer Reviewed
• [Journal Article] Structure-Activity Relationships of Synthesized Procyanidin, Oligomers : DPPH Radical Scavenging Activity and Maillard Reaction Inhibitory Activity (2010)
  • Author(s): Saito, A., Nakajima, N.
  • Journal Title: Heterocycles 80 Pages: 1081-1090
  • NAID: 40016991479
  • Peer Reviewed
• [Journal Article] Role of fatty acid chain length on the induction of apoptosis by newly synthesized catechin derivatives (2010)
  • Author(s): K.Ahmed
  • Journal Title: Chemico-Biological Interactions Volume: 185 Pages: 182-188
  • Peer Reviewed
• [Journal Article] Synthesis of Optically Pure Lactone-Metabolites Derived from Tea Catechins (2010)
  • Author(s): M.Hamada
  • Journal Title: Synthesis Pages: 1512-1520
  • Peer Reviewed
• [Journal Article] Structure-Activity Relationships of Synthesized Procyanidin, Oligomers : DPPH Radical Scavenging Activity and Maillard Reaction Inhibitory Activity (2010)
  • Author(s): Saito, A.
  • Journal Title: Heterocycles 80 Pages: 1081-1090
  • Peer Reviewed
• [Journal Article] Versatile synthesis of epicatechin series procyanidin oligomers, and their antioxidant and DNA polymerase inhibitory activity (2009)
  • Author(s): Saito, A.; Tanaka, A.; Mizushina, Y.; Nakajima, N.
  • Journal Title: Tetrahedron 65 Pages: 7422-7428
  • Peer Reviewed
• [Journal Article] Versatile synthesis of epicatechin series procyanidin oligomer, and their antioxidant and DNA polymerase inhibitory activity (2009)
  • Author(s): Saito, A.
  • Journal Title: Tetrahedron 65 Pages: 7422-7428
  • Peer Reviewed
• [Journal Article] Pyrogallol structure in polyphenol is involved in apoptosis-induction on HEK293T and K562 cells (2008)
  • Author(s): Mitsuhashi, S.; Saito, A.; Nakajima, N.; Shima, H.; Ubukata, M.
  • Journal Title: Molecules 13 Pages: 2998-3006
• [Journal Article] Synthetic of γ-valerolactones as the tea catechin metabolites (2008)
  • Author(s): Nakano, S.; Hamada, M.; Kishimoto, T.; Nakajima, N.
  • Journal Title: Heterocycles 76 Pages: 1001-1005
  • Peer Reviewed
• [Journal Article] Pyrogallol structure in polyphenol is involved in apoptosis-induction on HEK293T and K562 cells (2008)
  • Author(s): S. Mitsuhashi
  • Journal Title: Molecules 13 Pages: 2998-3006
  • Peer Reviewed
• [Journal Article] Synthesis of γ-valerolactones as the tea catechin metabolites (2008)
  • Author(s): S. Nakano
  • Journal Title: Heterocycles 76 Pages: 1001-1005
  • Peer Reviewed
• [Presentation] Synthesis and analysis of γ-valerolactones as the tea catechin metabolites (2010)
  • Author(s): Masahiro Hamada
  • Organizer: The Twenty First French-Japanese Symposium on Medicinal and Fine Chemistry(FJS2010)
  • Place of Presentation: Kyoto
  • Year and Date: 2010-05-10
• [Presentation] An efficient synthesis of procyanidin dimers using silyl-protecting group (2010)
  • Author(s): 堀川桂子, 中島範行
  • Organizer: Pacifichem 2010
  • Place of Presentation: Hawaii
• [Presentation] シリル型保護基を用いたカテキン化合物の合成 (2010)
  • Author(s): 中島範行
  • Organizer: 第8回北陸若手化学者談話会
  • Place of Presentation: 加賀
• [Presentation] 茶ポリフェノール代謝物の立体選択的合成と光学純度の決定 (2010)
  • Author(s): 濱田昌弘、古野愛、岸本崇生、中島範行
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] Synthesis and analysis of g-valerolactones as the tea catechin metabolites (2010)
  • Author(s): Masahiro Hamada, Ai Furuno, Takao Kishimoto, Noriyuki Nakajima
  • Organizer: The Twenty First French-Japanese Symposium on Medicinal and Fine Chemistry (FJS2010)
  • Place of Presentation: Kyoto
• [Presentation] シリル保護基を利用したカテキン誘導体の合成 (2009)
  • Author(s): 中島範行
  • Organizer: カテキン学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-09-09
• [Presentation] t-Butyldimethylsilyl基を保護基として用いたカテキン誘導体の合成 (2009)
  • Author(s): 中島範行
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] 光学活性茶ポリフェノール代謝物の立体選択的合成 (2009)
  • Author(s): 濱田昌弘
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] 柿や茶などのポリフェノールとその活用 (2009)
  • Author(s): 中島範行
  • Organizer: 射水ネットカフェコンソーシアム
  • Place of Presentation: 富山県立大学
  • Year and Date: 2009-01-31
• [Presentation] 茶カテキン光学活性ラクトン代謝物の立体的合成と光学純度の決定 (2009)
  • Author(s): 濱田昌弘、岸本崇生、中島範行
  • Organizer: 石川・富山県立大学合同シンポin芦原
  • Place of Presentation: 福井
• [Presentation] カテキンオリゴマーや誘導体の合成と活性 (2009)
  • Author(s): 中島範行
  • Organizer: 石川・富山県立大学合同シンポin芦原
  • Place of Presentation: 福井
• [Presentation] 茶カテキン光学活性ラクトン代謝物の効率的合成 (2009)
  • Author(s): 濱田昌弘、古野愛、中野荘介、岸本崇生、中島範行
  • Organizer: 日本複素環化学討論会
  • Place of Presentation: 柏
• [Presentation] 茶カテキンの光学活性ラクトン代謝物の立体選択的合成の効率化 (2009)
  • Author(s): 古野愛、中野荘介、濱田昌弘、岸本崇生、中島範行
  • Organizer: 有機合成北陸セミナー
  • Place of Presentation: 富山
• [Presentation] シリル基を保護基として用いたカテキン誘導体の合成2 (2009)
  • Author(s): 堀川桂子、濱田昌弘、岸本崇生、中島範行
  • Organizer: 有機合成北陸セミナー
  • Place of Presentation: 富山
• [Presentation] シリル保護基を利用したカテキン誘導体の合成 (2009)
  • Author(s): 中島範行
  • Organizer: 第6回日本カテキン学会
  • Place of Presentation: 名古屋
• [Presentation] 茶カテキン代謝物としてのγ-バレラクトンの合成 (2009)
  • Author(s): 中島範行
  • Organizer: 北陸化学者談話会2009
  • Place of Presentation: 福井
• [Presentation] 光学活性茶ポリフェノール代謝物の立体選択的合成 (2009)
  • Author(s): 濱田昌弘、中野荘介、古野愛、岸本崇生、中島範行
  • Organizer: 日本薬学会大会
  • Place of Presentation: 京都
• [Presentation] t-Butyldimethylsilyl (TBS)基を保護基として用いたカテキン誘導体の合成 (2009)
  • Author(s): 堀川桂子、竹川政範、濱田昌弘、岸本崇生、中島範行
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
• [Presentation] 茶カテキン類ラクトン代謝物の立体選択的合成 (2008)
  • Author(s): 濱田昌弘、中野荘介、岸本崇生、中島範行
  • Organizer: 創薬懇話会2008
  • Place of Presentation: 徳島
• [Remarks] ホームページ等
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• [Remarks]
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