Toward the total synthesis of a hybrid natural product containing oxabridged cis-decaline-macrolide and it's structure-activity relationships

• Project/Area Number: 22890175
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Kitasato University
• Principal Investigator: SUGAWARA Akihiro 北里大学, 大学院・感染制御科学府, 助教 (50581683)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥2,704,000 (Direct Cost: ¥2,080,000、Indirect Cost: ¥624,000); Fiscal Year 2011: ¥1,209,000 (Direct Cost: ¥930,000、Indirect Cost: ¥279,000); Fiscal Year 2010: ¥1,495,000 (Direct Cost: ¥1,150,000、Indirect Cost: ¥345,000)
• Keywords: シスデカリン / トリシクロ[5.3.1.^<1, 7> 0^<3, 8>]ウンデカン / ルミナミシン / 抗嫌気性菌活性 / 全合成 / 構造活性相関 / マクロライド / 酸素結束シスデカリン / エノールエーテル / オキサトリシクロウンデカン / 共役14員環エノールエーテル / 抗菌活性のスイッチング

Research Abstract

An efficient synthesis of the key framework of luminamicin, possessing vinyl enol ether, utilizing Stille coupling and Shiina macrolactonization was achieved. Additionally, synthesis of 11-oxatricyclo[5.3.1.^<1, 7> 0^<3, 8>] undecane framework, utilizing cascade Michael-aldol reaction and reaction of oxidative enol etherification was also developed.

Research Products

• [Journal Article] Effects of a novel nonantibiotic macrolide, EM900, on cytokine and mucin gene expression in a human airway epithelial cell line. (2011)
  • Author(s): Otsu K, Ishinaga H, Suzuki S, Sugawara A, Sunazuka T, Omura S, Jono H, Takeuchi K.
  • Journal Title: Pharmacology Volume: 88 Issue: 5-6 Pages: 327-32
  • DOI: 10.1159/000334339
  • Peer Reviewed
• [Journal Article] An inducible cell-cell fusion system with integrated ability to measure the efficiency and specificity of HIV-1 entry inhibitors (2011)
  • Author(s): Herschhorn A, Finzi A, Jones DM, Courter JR, Sugawara A
  • Journal Title: Sodroski JG PLoS One Volume: 6 Issue: 11 Pages: e26731-e26731
  • DOI: 10.1371/journal.pone.0026731
  • Peer Reviewed
• [Journal Article] Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag (2011)
  • Author(s): T.Hirose, T.Kasai, T.Akimoto, A.Endo, A.Sugawara, K.Nagasawa, K.Shiomi, S.Omura, T.Sunazuka
  • Journal Title: Tetrahedron Volume: 67 Issue: 35 Pages: 6633-6643
  • DOI: 10.1016/j.tet.2011.05.073
  • NAID: 130006995593
  • Peer Reviewed
• [Journal Article] Novel 12-membered non-antibiotic macrolides from erythromycin A ; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents (2011)
  • Author(s): Akihiro Sugawara, Akito Sueki, Tomoyasu Hirose, Kenichiro Nagai, Hiroaki Gouda, Shuichi Hirono, Hideaki Shima, Kiyoko S. Akagawa, Satoshi Omura, Toshiaki Sunazuka
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 21(11) Issue: 11 Pages: 3373-3376
  • DOI: 10.1016/j.bmcl.2011.04.004
  • Peer Reviewed
• [Journal Article] Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening (2011)
  • Author(s): Lalonde JM, Elban MA, Courter JR, Sugawara A, Soeta T, Madani N, Princiotto AM, Kwon YD, Kwong PD, Schon A, Freire E, Sodroski J
  • Journal Title: Bioorg & Med. Chem Volume: 19 Issue: 1 Pages: 91-101
  • DOI: 10.1016/j.bmc.2010.11.049
  • Peer Reviewed
• [Journal Article] Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening. (2011)
  • Author(s): Lalonde JM, Elban MA, Courter JR, Sugawara A, Soeta T, Madani N, Princiotto AM, Kwon YD, Kwong PD, Schon A, Freire E, Sodroski J, Smith AB 3rd.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 19 Pages: 91-101
  • Peer Reviewed
• [Journal Article] NMR spectroscopy and computational analysis of interaction between Serratia marcescens chitinase B and a dipeptide derived from natural-product cyclopentapeptide chitinase inhibitor argifin (2010)
  • Author(s): Hiroaki Gouda, Toshiaki Sunazuka, Tomoyasu Hirose, Kanami Iguchi, Noriyuki Yamaotsu, Akihiro Sugawara, Yoshihiko Noguchi, Yoshifumi Saito, Tsuyoshi Yamamoto, Takeshi Watanabe, Kazuro Shiomi, Satoshi Omura, Shuichi Hirono
  • Journal Title: Bioorg. Med. Chem Volume: 18(16) Issue: 16 Pages: 5835-5844
  • DOI: 10.1016/j.bmc.2010.06.093
  • Peer Reviewed
• [Journal Article] NMR spectroscopy and computational analysis of interaction between Serratia marcescens chitinase B and a dipeptide derived from natural-product cyclopentapeptide chitinase inhibitor argifin. (2010)
  • Author(s): Gouda H, Sunazuka T, Hirose T, Iguchi K, Yamaotsu N, Sugawara A, Noguchi Y, Saito Y, Yamamoto T, Watanabe T, Shiomi K, Omura S, Hirono S.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 18 Pages: 5835-5844
  • Peer Reviewed
• [Presentation] Novel 12-membered Non-antibiotic Macrolides ; EM900 Series As Novel Leads For Anti-inflammatory And/Or Immunomodulatory Agents (2011)
  • Author(s): Sugawara A, Sueki A, Hirose T, Nagai K, Gouda K, Hirono S, Shima H, Akagawa KS, Omura S, Sunazuka T
  • Organizer: 8th Asian Federation for Medicinal Chemistry(AFMC) International Medicinal Chemistry Symposium(AIMECS11)
  • Place of Presentation: Tokyo
• [Presentation] Novel 12-membered non-antibiotic macrolides ; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents (2011)
  • Author(s): Sugawara A, Sueki A, Hirose T, Nagai K, Gouda H, Hirono S, Shima H, Akagawa KS, . mura S, Sunazuka T
  • Organizer: ICCA12
  • Place of Presentation: Berlin, Germany
• [Presentation] 抗炎症作用に特化した新規12員環マクロライドEM900の創製と構造活性相関研究 (2011)
  • Author(s): 菅原章公, 末木啓人, 廣瀬友靖, 赤川清子, 大村智, 砂塚敏明
  • Organizer: バイオサイエンスフォーラム
  • Place of Presentation: 神奈川県(北里大学)
• [Presentation] 抗炎症作用に特化した新規12員環マクロライドEM900の創製と構造活性相関研究 (2011)
  • Author(s): 菅原章公, 末木啓人, 廣瀬友靖, 赤川清子, 大村智, 砂塚敏明
  • Organizer: 日本薬学会第131回年会
  • Place of Presentation: 静岡
• [Presentation] Novel 12-membered non-antibiotic macrolides ; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents (2011)
  • Author(s): Sugawara A, Sueki A, Hirose T, Nagai K, Gouda H, Hirono S, Shima H, Akagawa KS, Omura S, Sunazuka T
  • Organizer: 8^<th> Asian Federation for Medicinal Chemistry (AFMC) International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo, Japan
• [Presentation] 抗炎症作用に特化した新規12員環マクロライドの創製と構造活性相関研究 (2011)
  • Author(s): 菅原章公、末木啓人、廣瀬友靖、赤川清子、大村智、砂塚敏明
  • Organizer: 日本薬学会第131回年会
  • Place of Presentation: 静岡
• [Presentation] 抗炎症作用に特化した新規12員環マクロライドEM900の創製と構造活性相関研究 (2010)
  • Author(s): 菅原章公, 末木啓人, 廣瀬友靖, 赤川清子, 大村智, 砂塚敏明
  • 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
• [Presentation] 抗炎症作用に特化した新規12員環マクロライドの創製と構造活性相関研究 (2010)
  • Author(s): 菅原章公、末木啓人、廣瀬友靖、赤川清子、大村智、砂塚敏明
  • 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
• [Remarks]
  • URL: http://seibutuyuuki.sakura.ne.jp/
• [Remarks]
  • URL: http://seibutuyuuki.sakura.ne.jp/