Stereostructure and synthetic study of dilactone macrolide luminamicin, an anaerobic antibiotic

• Project/Area Number: 16590012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Kitasato University
• Principal Investigator: SUNAZUKA Toshiaki Kitasato University, Kitasato Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (30226592)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Antibiotics / Organic synthesis / Infectious disease / Bioactive / Organic chemistry / Structure determination / 絶対構造決定 / 不斉全合成 / マクロライド / 抗感染症薬 / 生理活性天然物 / 収束的合成 / ルミナミシン

Research Abstract

In the course of screening for antianaerobic antibiotics of actinomycete origin, we have found a new antibiotic, luminamicin, which showed antibacterial activity against anaerobic bacteria, especially against Clostridium sp. Its architectural feature is a decalin ring system fused to a 10-membered macrolactone which in turn is fused to a 14-membered macrolactone possessing an enol ether in conjugation with an unsaturated cyclic anhydride functionality, and this compound has 11 asymmetric centers.
The absolute stereostructure of luminamicin, an anaerobic antibiotic, has been determined by using conformational analysis via high-temperature molecular dynamics, NMR spectroscopy, and the modified Mosher method. We also have synthesized this molecule. We divide the three parts (northern part, middle part, and southern part). 3,4-Disubstituted furan has constructed from 4-phenyloxazole and alkynal via Diels-Alder Retro-Diels-Alder reaction. And middle part has constructed via Frdter's alkylation with BOMC1 and Reformatsky reaction. And also, the construction of oxa-bridge have formed by intramolecular Michael addition and intermolecular Aldol reaction.

Research Products

• [Journal Article] Stereostructure of luminamicin, an anaerobic antibiotic, via molecular dynamics, NMR spectroscopy, and the modified Mosher mehod (2005)
  • Author(s): 砂塚 敏明
  • Journal Title: Proceeding of the National Academy of Sciences of United States of America 102 Pages: 18286-18291
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stereostructure of luminamicin, an anaerobic antibiotic, via molecular dynamics, NMR spectroscopy, and the modified Mosher mehod (2005)
  • Author(s): Gouda, H., Sunazuka, T., Handa, M., Ui, H., Yamamoto, D., Monma, S., Hirono, H., Omura, S.
  • Journal Title: Proc.Natl, Acad.Sci.USA 102 Pages: 18286-18291
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stereostructure of luminamicin, an anaerobic antibiotic, via molecular dynamics, NMR spectroscopy, and the modified Mosher method (2005)
  • Author(s): 砂塚 敏明
  • Journal Title: Proceeding of the National Academy of Sciences of United States of America 51 Pages: 18286-18291