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

厌氧抗生素双内酯大环内酯发光霉素的立体结构及合成研究

• 批准号: 16590012
• 负责人: SUNAZUKA Toshiaki
• 金额: $ 2.24万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590012/
• 关键词: 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

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.

在筛选放线菌来源的抗厌氧抗生素的过程中，我们发现了一种新的抗生素，鲁米诺霉素，它对厌氧细菌，特别是对梭菌显示出抗菌活性。它的结构特征是十氢萘环系统与10元大环内酯稠合，10元大环内酯又与14元大环内酯稠合，14元大环内酯具有与不饱和环酸酐官能团共轭的烯醇醚，利用高温分子动力学、核磁共振波谱和改进的Mosher方法对厌氧抗生素鲁米诺霉素进行了构象分析，确定了其绝对立体结构。我们也合成了这个分子。我们把它分成三部分（北方部分、中部部分和南部部分）。以4-苯基恶唑和炔醛为原料，通过Diels-桤木逆Diels-桤木反应合成了3，4-二取代呋喃。中间部分通过Frdter与BOMC 1的烷基化反应和Reformatsky反应构建。分子内的Michael加成和分子间的Aldol反应也形成了氧杂桥结构。

项目成果

Stereostructure of luminamicin, an anaerobic antibiotic, via molecular dynamics, NMR spectroscopy, and the modified Mosher method

• DOI: 10.1073/pnas.0508425102
• 发表时间: 2005-12-20
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Gouda, H;Sunazuka, T;Omura, S
• 通讯作者: Omura, S