Asymmetric synthetic studies on jiadifenin, neurotrophic compound

• Project/Area Number: 19790027
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: HARADA Kenichi Tokushima Bunri University, 薬学部, 助教 (70441590)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,710,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 合成化学 / 有機合成化学 / ジアジフェニン / 神経栄養因子 / アルツハイマー病 / 神経突起伸展促進活性 / パラジウム触媒 / Tsuji-Trost反応 / 構造活性相関 / 神経突起伸展促進 / パラシウム触媒 / イリジウム触媒 / Mizoroki-Heck反応

Research Abstract

An efficient synthetic route for neurotrophic jiadifenin has been established. The key steps were Pd-catalyzed Mizoroki-Heck reaction for cyclopentene ring and successive Tsuji-Trost reaction and lactonization for center and lactone rings.

Research Products

• [Journal Article] NGF-potentiating vibsane-type diterpenoids from Viburnum sieboldii (2010)
  • Author(s): M. Kubo, Y. Kishimoto, K. Harada, H. Hioki, Y. Fukuyama
  • Journal Title: Bioorg. Med. Chem. Lett. 20 Pages: 2566-2571
• [Journal Article] Synthesis of riccardin C and its seven analogues. Part 1: The role of their phenolic hydroxy groups as LXR-agonists (2009)
  • Author(s): H. Hioki, N. shima, K. Kawaguchi, K. Harada, M. Kubo, T. Esumi, T. Nishimaki-Mogami, J. Sawada, T. Hashimoto, Y. Asakawa, Y. Fukyama
  • Journal Title: Bioorg. Med. Chem. Lett. 19 Pages: 738-741
• [Journal Article] Novel NGF-potentiating diterpenoids from a Brazilian medicinal plant, Ptychopetalum olacoides (2009)
  • Author(s): W. Tang, M. Kubo, K. Harada, H. Hioki, Y. Fukyama
  • Journal Title: Bioorg. Med. Chem. Lett. 19 Pages: 882-886
• [Journal Article] Total Synthesis of Pseudodehydrothyrsiferol (2009)
  • Author(s): H. Hioki, M. Motosue, Y. Mizutani, A. Noda, T. Shimoda, M. Kubo, K. Harada, Y. Fukuyama, M. Kodama
  • Journal Title: Org. Lett. 11 Pages: 579-582
• [Journal Article] Isolation, synthesis, and outgrowth- promoting activity of illicinin A from the flowers of Illicium anisatum (2009)
  • Author(s): S. Takaoka, N. Takaoka, Y. Minoshima, J. -M. Huang, M. Kubo, K. Harada, H. Hioki, Y. Fukuyama
  • Journal Title: Tetrahedron 65 Pages: 8354-8361
• [Journal Article] Novel pentacyclic seco-prezizaane-type sesquiterpenoids with neurotrophic properties from Illicium jiadifengpi (2009)
  • Author(s): M. Kubo, C. Okada, J. -M. Huang, K. Harada, H. Hioki, Y. Fukuyama
  • Journal Title: Org. Lett. 11 Pages: 5190-5193
• [Journal Article] Discovery of hydrolytic catalysts in a peptidocalixarene library by binding assay with a transition state analogue for the hydrolysis (2009)
  • Author(s): H. Hioki, R. Nishimoto, K. Kawaguchi, M. Kubo, K. Harada, Y. Fukuyama
  • Journal Title: Chem. Comm. Pages: 7194-7196
• [Journal Article] Isolation, synthesis, and outgrowth-promoting activity of illicinin A from the flowers of Illicium anisatum (2009)
  • Author(s): Shigeki Takaoka
  • Journal Title: Tetrahedron 65 Pages: 8354-8361
  • Peer Reviewed
• [Journal Article] Novel pentacyclic seco-prezizaane-type sesquiterpenoids with neurotrophic properties from Illicium jiadifengpi (2009)
  • Author(s): Miwa Kubo
  • Journal Title: Organic Letters 11 Pages: 5190-5193
  • Peer Reviewed
• [Journal Article] Discovery of hydrolytic catalysts in a peptidocalixarene library by binding assay with a transition state analogue for the hydrolysis (2009)
  • Author(s): Hideaki Hioki
  • Journal Title: Chemical Communications Pages: 7194-7196
  • Peer Reviewed
• [Journal Article] Total synthesis of pseudodehydrothyrsiferol (2009)
  • Author(s): Hideaki Hioki
  • Journal Title: Organic Letters 11 Pages: 579-582
  • Peer Reviewed
• [Journal Article] Synthesis of riccardin C and its seven analogues. Part 1 : The role of their phenolic hydroxy groups as LXRa agonists (2009)
  • Author(s): Hideaki Hioki
  • Journal Title: Bioorganic and Medicinal Chemistry Letters 19 Pages: 738-741
  • Peer Reviewed
• [Journal Article] Novel NGF-potentiating diterpenoids from a Brazilian medicinal plant, Ptychopetalum olacoides (2009)
  • Author(s): Miwa Kubo
  • Journal Title: Bioorg. Med. Chem. Lett. 19 Pages: 882-886
  • Peer Reviewed
• [Journal Article] Two New Sesquiterpenoids and Two New Prenylated Phenylpropanoids from Illicium fargesii, and Neuroprotective Activity of Macranthol (2008)
  • Author(s): M. Moriyama, J. -M. Huang, C. -S. Yang, M. Kubo, K. Harada, H. Hioki, Y.
  • Journal Title: Fukuyama, Chem. Pharm. Bull. 56 Pages: 1201-1204
  • NAID: 110006838336
• [Journal Article] Synthesis of (-)-talaumidin, a neurotrophic 2, 5-biaryl-3, 4-dimethyltetrahydrofuran lignan, and its stereoisomers (2008)
  • Author(s): Y. Fukuyama, K. Harada, T. Esumi, D. Hojyo, Y. Kujime, N. Kubo, M. Kubo, H. Hioki
  • Journal Title: Heterocycles. 76 Pages: 551-567
• [Journal Article] Solid-phase combinatorial synthesis of 2-arylquinazolines and 2-arylquinazolinones by an 4-alkoxyaniline linker (2008)
  • Author(s): H. Hioki, K. Matsushita, S. Nakamura, H. Horiuchi, M. Kubo, K. Harada, Y.
  • Journal Title: Fukuyama, J. Comb. Chem. 10 Pages: 620-623
• [Journal Article] Clerodane Diterpenoids with NGF-Potentiating Activity from Ptychopetalum olacoides (2008)
  • Author(s): W. Tang, H. Hioki, K. Harada, M. Kubo, Y.
  • Journal Title: Fukuyama, J. Nat. Prod. 71 Pages: 1760-1763
• [Journal Article] Synthesis of (-)-talaumidin, aneurotrophic 2,5-dimethyltetrahidrofirran lignan, and its stereoisimers (2008)
  • Author(s): Yoshiyasu Fukuyama
  • Journal Title: Heterocycles 76 Pages: 551-567
  • Peer Reviewed
• [Journal Article] Two New Sesquiterpenoids and Two New Prenylated Phenylpropanoids from Illicium fargesii, and Neuroprotective Activity of Macranthol (2008)
  • Author(s): Miyako Moriyama
  • Journal Title: Chem. Pharm. Bull. 56 Pages: 1201-1204
  • Peer Reviewed
• [Journal Article] Solid-phase combinatorial synthesis of 2-arylquinazolines and 2-arylquinazolinones by an 4-alkoxyaniline linker (2008)
  • Author(s): Hideaki Hioki
  • Journal Title: J. Comb. Chem. 10 Pages: 620-623
  • Peer Reviewed
• [Journal Article] Clerodane Diterpenoids with NGF-Potentiating Activity from Ptychopetalum olacoides (2008)
  • Author(s): Wanxia Tang
  • Journal Title: J. Nat. Prod. 71 Pages: 1760-1763
  • Peer Reviewed
• [Journal Article] An efficient synthesis of the CD rings model for merrilactone A (2007)
  • Author(s): K. Harada, H. Ito, H. Hioki, Y.
  • Journal Title: Fukuyama, Tetrahedron Lett. 48 Pages: 6105-6108
• [Journal Article] Solid-phase combinatorial synthesis of benzothiazoles, benzimidazoles, and benzoxazoles using a traceless linker (2007)
  • Author(s): H. Hioki, K. Matsushita, M. Kubo, K. Harada, M. Kodama, Y. Fukuyama
  • Journal Title: Tetrahedron 63 Pages: 11315-11324
• [Journal Article] Antioxidant Phenylpropanoid-Substituted Epi- catechins from Trichilia catigua (2007)
  • Author(s): W. Tang, H. Hioki, K. Harada, M. Kubo, Y.
  • Journal Title: Fukuyama, J. Nat. Prod. 70 Pages: 2010-2013
• [Journal Article] An efficient synthesis oflhe CD rings model for merrilactone A (2007)
  • Author(s): Kenichi Harada
  • Journal Title: Tetrahedron Letters 48 Pages: 6105-6108
  • Peer Reviewed
• [Journal Article] Solid-phase combinatorial synthesis of benzothiazoles, benzimidazoles, and benzoxazoles using a traceless linker (2007)
  • Author(s): Hideaki Hioki
  • Journal Title: Tetrahedron 63 Pages: 11315-11324
  • Peer Reviewed
• [Journal Article] Antioxidant Phenylpropanoid-Substituted Epicatechins from trichilia catigua (2007)
  • Author(s): Wanxia Tang
  • Journal Title: J. Nat. Prod. 70 Pages: 2010-2013
  • Peer Reviewed
• [Presentation] Pd触媒反応を活用した神経栄養因子様物質ジアジフェニンの合成研究 (2010)
  • Author(s): 今井顕子
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山市
  • Year and Date: 2010-03-29
• [Presentation] 神経栄養因子様物質ジアジフェニンの合成研究(2) (2009)
  • Author(s): 宇都和遥
  • Organizer: 第129回日本薬学会年会
  • Place of Presentation: 京都市
  • Year and Date: 2009-03-26
• [Presentation] 神経栄養因子様物質ジアジフェニンの合成研究 (2008)
  • Author(s): 宇都和遥
  • Organizer: 第128年会日本薬学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2008-03-26
• [Presentation] 神経栄養因子様物質ジアジフェニンの合成研究
  • Organizer: 日本薬学会第128年会
• [Presentation] 神経栄養因子様物質ジアジフェニンの合成研究(2)
  • Organizer: 日本薬学会第129年会
• [Presentation] 神経栄養因子様物質ジアジフェニンの合成研究
  • Organizer: 第53回 香料・テルペンおよび精油化学に関する討論会
• [Presentation] Pd触媒反応を活用した神経栄養因子様物質ジアジフェニンの合成研究
  • Organizer: 日本薬学会第130年会
• [Remarks]
  • URL: http://p.bunri-u.ac.jp/~fukuyama/fukuyama/index.htm
• [Remarks]
  • URL: http://p.bunri-u.ac.jp/~fukuyama/fukuyama/index.html
• [Remarks]
  • URL: http://p.bunri-u.ac.jp/~fukuyama/fhkuyama/japanese/jpindex.html