Synthetic Studies on novel fucosidase and rhamnosidase inhibitors

• Project/Area Number: 24590138
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: University of Toyama
• Principal Investigator: TOYOOKA naoki 富山大学, 大学院理工学研究部(工学), 教授 (10217565)
• Co-Investigator(Kenkyū-buntansha): KATO Atsushi 富山大学, 附属病院, 准教授 (60303236)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: fucosidase / rhamnosidase / inhibitors / エナンチオダイバージェントストラテジー / ポリヒドロキシピロリチジン / フコシダーゼ / ラムノシダーゼ / フコシダーゼ阻害剤 / 擬態 / 新規アミド型化合物

Outline of Final Research Achievements

Much attention has been paid to the synthesis of inhibitors of fucosidase because of their potential as therapeutic agents. We succeeded in the synthesis of a fucose-mimetic structure of novel fucosidase inhibitor (IC50 5 nM) .
We also established a flexible and enantiodivergent synthesis of polyhydroxylated pyrrolizines, and one of the synthetic compound showed moderate inhibitory activity against fucosidase.

Research Products

• [Journal Article] Enantiodivergent strategy for the synthesis of polyhydroxylated pyrrolizidines and evaluation of their inhibitory activities against glycosidases (2015)
  • Author(s): Minehira, D.*; Okada, T.; Iwaki, R.; Kato, A.; Adachi, I.; Toyooka, N.*
  • Journal Title: Tetrahedron Lett. Volume: 56 Issue: 2 Pages: 331-334
  • DOI: 10.1016/j.tetlet.2014.11.087
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthesis and biological evaluation of N-(2-fluorophenyl)-2β-deoxyfuconojirimycin acetamide as a potent inhibitor for α-L-fucosidases (2013)
  • Author(s): Kato, A.*; Okaki, T.; Ifuku, S.; Sato, K.; Hirokami, Y.; Iwaki, R.; Kamori, A.; Nakagawa, S.; Adachi, I.; Kiria, P. G.; Onomura, O.; Minato, D.; Sugimoto, K.; Matsuya, Y.; Toyooka, N.*
  • Journal Title: Bioorg. Med. Chem. Volume: 21 Issue: 21 Pages: 6565-6573
  • DOI: 10.1016/j.bmc.2013.08.028
  • Peer Reviewed
• [Journal Article] Synthesis of Phenylalkyl Substituted Polyhydroxypiperidines as Potent Inhibitors for α-L-Fucosidases (2013)
  • Author(s): Saka, T.; Okaki, T.; Ifuku, S.; Yamashita, Y.; Sato, K.; Miyawaki, S.; Kamori, A.; Kato, A.*; Adachi, I.; Kiria, P. G.; Onomura, O.; Minato, D.; Sugimoto, K.; Matsuya, Y.; Toyooka, N.*
  • Journal Title: Tetrahedron Volume: 69 Issue: 49 Pages: 10653-10661
  • DOI: 10.1016/j.tet.2013.10.006
  • Peer Reviewed
• [Presentation] フコシダーゼ阻害が期待されるアミド型イミノ糖の合成および活性評価 (2013)
  • Author(s): 伊福 翔平・岡城 徹・中川 進平・加藤 敦・足立 伊佐雄・Peter G. Kirira・尾野村 治・豊岡 尚樹
  • Organizer: 第４３回複素環化学討論会
  • Place of Presentation: 岐阜
• [Presentation] 強力なフコシダーゼ阻害活性を有するポリヒドロキシピペリジン誘導体の合成 (2013)
  • Author(s): 岡城 徹, 坂 知樹, 湊 大志郎, 杉本 健士, 松谷 裕二, 中川 進平, 山下 侑子, 加藤 敦, 足立 伊佐雄, 手塚 康弘, Peter G. Kirira, 尾野村 治, 豊岡尚樹
  • Organizer: 日本薬学会第１３３年会
  • Place of Presentation: 横浜
• [Presentation] フコシダーゼ阻害が期待されるアミド型イミノ糖の合成および活性評価 (2013)
  • Author(s): 伊福 翔平・岡城 徹・中川 進平・加藤 敦・足立 伊佐雄・Peter G. Kirira・尾野村 治・豊岡 尚樹
  • Organizer: 日本薬学会第１３３年会
  • Place of Presentation: 横浜
• [Presentation] Synthesis of Novel Iminosugar Derivatives with Inhibitory Effects on α-Fucosidase (2012)
  • Author(s): Toru Okaki, Tomoki Saka, Daishiro Minato, Kenji Sugimoto, Yuji Matsuya, Shinpei Nakagawa, Yukiko Yamashita, Atsushi Kato, Isao Adachi, Peter G. Kirira, Osamu Onomura, Naoki Toyooka
  • Organizer: The 12th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-12)
  • Place of Presentation: Kyoto