Synthesis and Activity of Tea Catechins Lactone-Metabolite

• Project/Area Number: 24590014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Toyama Prefectural University
• Principal Investigator: NAKAJIMA NORIYUKI 富山県立大学, 工学部, 教授 (40188959)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 茶カテキン / 代謝物 / γ-ブチロラクトン化合物 / ガン細胞増殖阻害増強効果 / 白血病細胞HL-60 / カテキン / 化学合成 / 生理活性

Outline of Final Research Achievements

Tea catechins such as epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate changes many metabolites including γ-valerolactone compounds through metabolic pathways in the human body.
Fourteen of these γ-valerolactone metabolite analogues were synthesized as the optically active authentic standards and these activities are examined. Furthermore, we found out that the mixture of EGCG (flavan-3-ol) and its metabolite γ-valerolactone compounds inhibit proliferation of HL-60 cells, human promyelocytic leukemia cells.

Research Products

• [Journal Article] Biomimetic oxidative coupling of sinapyl acetate by silver oxide: preferential formation of β-O-4 type structures (2015)
  • Author(s): Takao Kishimoto, Nana Takahashi, Masahiro Hamada, and Noriyuki Nakajima
  • Journal Title: Journal of Agricultural and Food Chemistry Volume: 63 Issue: 8 Pages: 2277-2283
  • DOI: 10.1021/jf506111q
  • Peer Reviewed
• [Journal Article] Role of 2,3-cis Structure of (-)-Epicatechin-3,5-O-digallate in Inhibition of HeLa S3 Cell Proliferation (2015)
  • Author(s): Kazuki Mori, Yoshihiro Ayano, Yoshitomo Hamada, Taichi Hojima, Ryuta Tanaka, Yusuke Higashino, Mayu Izuno , Taisuke Okamoto, Takashi Kawasaki, Masahiro Hamada, Noriyuki Nakajima* and Akiko Saito
  • Journal Title: Natural Products Chemistry & Researc. Volume: 3 Issue: 3 Pages: 172-178
  • DOI: 10.4172/2329-6836.1000172
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Synthesis of Tea Catechins Lactone-Metabolite Analogues with a 2’-Hydroxyphenyl Group (2014)
  • Author(s): Masahiro Hamada, Shunichi Naruse, Misaki Wada, Takao Kishimoto, and Noriyuki Nakajima
  • Journal Title: Synthesis Volume: 46 Issue: 13 Pages: 1779-1787
  • DOI: 10.1055/s-0033-1341083
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of a New Synthetic Strategy For Procyanidin Dimer Condensation Using Peracetylated Electrophiles (2014)
  • Author(s): Sayaka Ishihara, Syoma Doi, Kota Harui, Taisuke Okamoto, Shuhei Okamoto, Joji Uenishi, Takashi Kawasaki, Noriyuki Nakajima, and Akiko Saito
  • Journal Title: Heterocycles Volume: 88 Issue: 2 Pages: 1595-1602
  • DOI: 10.3987/com-13-s(s)103
  • Peer Reviewed
• [Journal Article] Inhibitory activity of synthesized acetylated procyanidin B1 analogs against HeLa S3 cells proliferation (2014)
  • Author(s): Syuhei Okamoto, Sayaka Ishihara, Taisuke Okamoto, Syoma Doi, Kota Harui, Yusuke Higashino, Takashi Kawasaki, Noriyuki Nakajima, Akiko Saito
  • Journal Title: Molecules Volume: 19 Issue: 2 Pages: 1775-1785
  • DOI: 10.3390/molecules19021775
  • Peer Reviewed
• [Journal Article] Molecular weight distributions of acetylated lignocellulosic biomasses recovered from an ionic liquid system (2013)
  • Author(s): Chen Qu, Takao Kishimoto*, Masahiro Hamada and Noriyuki Nakajima.
  • Journal Title: Holzforschung Volume: 67 Pages: 721-726
  • Peer Reviewed
• [Journal Article] Short and Stereocontrolled cyclic PolygrycerolsSynthesis Using BF3・OEt2 Mediated Intermolecular Epoxide-Opening Reaction (2013)
  • Author(s): Masahiro Hamada, Takao Kishimoto, and Noriyuki Nakajima
  • Journal Title: Heterocycles Volume: 86 Issue: 2 Pages: 1533-1539
  • DOI: 10.3987/com-12-s(n)67
  • Peer Reviewed
• [Journal Article] Isolation of a new phlorotannin, a potent inhibitor of carbohydrate-hydrolyzing enzymes, from the brown alga Sargassum patens (2012)
  • Author(s): Yasuko Konishi, Natsuko Watanabe, Noriyuki Nakajima, Toshiyuki Sakaki, Takane Katayama, Toshiki Enomoto,
  • Journal Title: Journal of Agricultural and Food Chemistry Volume: 60 Issue: 22 Pages: 5565-5570
  • DOI: 10.1021/jf300165j
  • Peer Reviewed
• [Journal Article] ポリグリセロールやその脂肪酸エステルの合成と油脂ゲル化作用 (2012)
  • Author(s): 中島範行、濱田昌弘
  • Journal Title: 有機合成化学協会誌 Volume: 70 Pages: 742-753
  • NAID: 10030835487
• [Journal Article] Dissolution and acetylation of ball-milled lignocellulosic biomass in ionic liquids at room temperature: application to nuclear magnetic resonance analysis of cell-wall components (2012)
  • Author(s): Chen Qu, Takao Kishimoto, Masahiro Hamada, and Noriyuki Nakajima
  • Journal Title: Holzforschung Volume: 67 Pages: 25-32
  • Peer Reviewed
• [Presentation] 脂肪鎖を導入したフラバン-3-オール誘導体の合成とガン細胞増殖抑制活性 (2015)
  • Author(s): 綾野義博, 森一起, 平井瑞輝, 中島範行, 齊藤安貴子
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 下部ユニットをアセチル化したフラバン-3-オール2量体の合成と生物活性評価 (2015)
  • Author(s): 法島太一, 濱田義知, 中島範行, 齊藤安貴子
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] プロアントシアニジンの構造-活性相関研究：上部ユニットB環の水酸基の重要性 (2015)
  • Author(s): 濱田義知、綾野義博、小芦貴弘、伊藤孝太郎、徳永将大、高野翔太、中島範行、齊藤安貴子,
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] HeLa S3 細胞増殖抑制活性に対する（－）-Epicatechin-3,5-O-digallate の2,3-cis 構造の重要性 (2015)
  • Author(s): 森一起， 綾野義博， 濱田義知， 法島太一，田中隆太，赤坂吉績，中島範行，齊藤安貴子
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] プロアントシアニジンの立体選択的合成研究を軸とした構造-活性相関研究と化学生物学研究 (2014)
  • Author(s): 東野雄祐, 綾野義博, 濱田義知, 森一起, 小芦貴弘, 泉野麻友, 春井宏太, 法島太一, 柴崎亨, 野呂健太, 奥谷晃平, 土井翔馬, 岡本修平, 石原沙也加, 岡本泰輔, 水品善之, 吉仲由之, 川崎崇, 中島範行, 齊藤安貴子
  • Organizer: 第56回 天然有機化合物討論会
  • Place of Presentation: 高知
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Stereo- and regio- controlled synthesis of proanthocyanidines under intramolecular coupling method (2014)
  • Author(s): Yusuke Higashino, Yoshitomo Hamada, Taisuke Okamoto, Syoma Doi, Sayaka Ishihara, Kazuki Mori, Shota Takano, Taich Hojima, Toru Shibazaki, Takashi Kawasaki, Akiko Saito, Noriyuki Nakajima
  • Organizer: The twenty-fourth French-Japanese Symposium on Medicinal and Fine Chemistry (FJS 2014)
  • Place of Presentation: フランス、リヨン
  • Year and Date: 2014-09-15 – 2014-09-17
• [Presentation] 2'位に水酸基を有する茶カテキン代謝物の合成 (2014)
  • Author(s): 濱田昌弘, 成瀬俊一, 和田岬, 岸本崇生, 中島範行
  • Organizer: 第44回複素環化学討論会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Structure-Activity-Relationship Studies of Flavan-3-ol Derivatives: Inhibitory Activity of Cancer Cell Proliferation and Antimicrobial Activity (2014)
  • Author(s): Kota Harui, Yoshihiro Ayano, Syuhei Okamoto, Syoma Doi, Mayu Izuno, Atsushi Horikawa, Takahiro Koashi, Akito Yoshimi, Kenta Noro, Takashi Kawasaki, Noriyuki Nakajima and Akiko Saito
  • Organizer: The 27th International Conference on Polyphenols (ICP2014)
  • Place of Presentation: 名古屋
  • Year and Date: 2014-09-02 – 2014-09-06
• [Presentation] Stereo- and regio- controlled synthetic studies of proanthocyanidins and their inhibitory activities against cancer cell proliferation (2014)
  • Author(s): Yusuke Higashino, Yoshitomo Hamada, Taisuke Okamoto, Syoma Doi, Sayaka Ishihara, Kazuki Mori, Shota Takano, Taich Hojima, Toru Shibazaki, Takashi Kawasaki, Nakajima Noriyuki and Akiko Saito
  • Organizer: The 27th International Conference on Polyphenols (ICP2014)
  • Place of Presentation: 名古屋
  • Year and Date: 2014-09-02 – 2014-09-06
• [Presentation] Synthesis and Activity of γ-Valerolactones as the Tea Catechin Metabolites (2014)
  • Author(s): Shunichi Naruse, Masahiro Hamada, Takao Kishimoto, Kohei Okutani, Takayuki Tomita, Syuhei Okamoto, Akiko Saito and Noriyuki Nakajima
  • Organizer: The 27th International Conference on Polyphenols (ICP2014)
  • Place of Presentation: 名古屋
  • Year and Date: 2014-09-02 – 2014-09-06
• [Presentation] 5位を修飾したフラバン-3-オールの効率的合成法の開発と構造-活性相関研究 (2014)
  • Author(s): 森一起, 綾野義博, 水品善之, 法島太一, 中島範行, 齊藤安貴子
  • Organizer: 第8回日本ポリフェノール学会
  • Place of Presentation: 東京
  • Year and Date: 2014-08-08
• [Presentation] 3位, あるいは, 5位に位置選択的に脂肪酸を導入したflavan-3-olの合成と脂肪鎖の導入位置による生物活性の変化 (2014)
  • Author(s): 小芦貴弘, 綾野義博, 野呂健太, 森一起, 東野雄祐, 法島太一, 岡本泰輔, 中島範行, 齊藤安貴子
  • Organizer: 新規素材探索研究会2014
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-05
• [Presentation] カテキン類の腸内細菌代謝物とEGCGの混合物は、ヒト骨髄性白血病細胞HL-60の増殖を強く阻害する (2014)
  • Author(s): 綾野義博, 奥谷晃平, 富田貴之, 濱田昌弘, 中島範行, 齊藤安貴子
  • Organizer: 新規素材探索研究会2014
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-05
• [Presentation] アセチル化求電子体を用いたプロアントシアニジンの合成研究 (2013)
  • Author(s): 植西譲二, 岡本泰輔, 森口正太郎, 岡本修平, 土井翔馬, 石原沙也加, 中島範行, 齊藤安貴子
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
• [Presentation] プロシアニジンオリゴマーの構造―活性相関 (2013)
  • Author(s): 岡本修平, 石原沙也加, 岡本泰輔, 土井翔馬, 泉野麻友, 中島範行, 齊藤安貴子
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
• [Presentation] プロシアニジンオリゴマーのプローブ化研究 (2013)
  • Author(s): 岡本泰輔, 東野雄祐, 濱田義知, 石原沙也加, 岡本修平, 土井翔馬, 中島範行, 齊藤安貴子
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
• [Presentation] 2'位に水酸基を有する茶カテキン代謝物の合成 (2013)
  • Author(s): 成瀬俊一、濱田昌弘、岸本崇生、中島範行
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
• [Presentation] プロアントシアニジンの化学：効率的合成法の開発ならびに化学生物学研究 (2012)
  • Author(s): 岡本泰輔、岡本修平、土井翔馬、石原沙也加、東野雄祐、泉野麻友、中島範行、齊藤安貴子
  • Organizer: 第54回天然物化学討論会
  • Place of Presentation: 東京
• [Presentation] 2' 位に水酸基を有するカテキン代謝物の合成 (2012)
  • Author(s): 成瀬俊一、和田岬、濱田昌弘、岸本崇生、中島範行
  • Organizer: 平成24年度有機合成化学北陸セミナー
  • Place of Presentation: 富山
• [Presentation] Stereoselective synthesis of proanthocyanidins, and their SAR study (2012)
  • Author(s): Sayaka Ishihara, Taisuke Okamoto, Syoma Doi, Syuhei Okamoto, Yusuke Higashino, Noriyuki Nakajima, Akiko Saito
  • Organizer: International Kyoto Conference on New Aspect of Organic Chemistry (IKCOC)
  • Place of Presentation: kyoto
• [Presentation] Synthesis of tea catechin derivatives
  • Author(s): Shunichi Naruse, Takao Kishimoto, Masahiro Hamada and Noriyuki Nakajima
  • Organizer: 23rd French-Japanese Symposium on medicinal and fine chemistry (FJS2013)
  • Place of Presentation: 長崎
• [Presentation] プロアントシアニジンの上部ユニットをアセチル化した誘導体の合成と生物活性試験
  • Author(s): 土井翔馬, 岡本修平, 春井宏太, 石原沙也加, 岡本泰輔, 高野 祥太, 中島範行, 齊藤安貴子
  • Organizer: 新規素材探索研究会2013
  • Place of Presentation: 横浜
• [Presentation] プロシアニジンのプローブ合成と構造－活性相関研究
  • Author(s): 春井宏太, 岡本泰輔, 石原沙也, 加堀川敦史, 中島範行, 齋藤安貴子
  • Organizer: 第43回複素環化学討論会
  • Place of Presentation: 岐阜
• [Presentation] ガロイル基で修飾したＢタイプ・プロシアニジンの細胞増殖抑制活性
  • Author(s): 石原沙也加, 岡本修平, 土井翔馬, 岡本泰輔, 綾野義博, 中島範行, 齋藤安貴子
  • Organizer: 第43回複素環化学討論会
  • Place of Presentation: 岐阜
• [Presentation] Procyanidin-B1-3,3"-di-O-gallateはEGCGと異なる作用でHeLa S3細胞の増殖を阻害する？
  • Author(s): 石原沙也加、綾野義博、岡本修平、土井翔馬、岡本泰輔、須藤龍彦、長田裕之、中島範行、齊藤 安貴子
  • Organizer: 2012 年度日本農芸化学会関西支部例会
  • Place of Presentation: 京都
• [Patent(Industrial Property Rights)] 特許 (2014)
  • Inventor(s): 中島範行, 川崎安貴子
  • Industrial Property Rights Holder: 富山県, 川崎安貴子
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-093523
  • Filing Date: 2014-04-30
• [Patent(Industrial Property Rights)] ガン細胞増殖阻害作用増強剤とその製造方法及び食品 (2014)
  • Inventor(s): 中島範行、川崎安貴子
  • Industrial Property Rights Holder: 中島範行、川崎安貴子
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-093523
  • Filing Date: 2014-04-30