THE STEREOSPECIFIC SYNTHESIS OF AMINOSUGAR ANTIBIOTICS

氨基糖抗生素的立体定向合成

• 批准号: 3288512
• 负责人: PHILIP P GARNER
• 金额: $ 9.22万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1988-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3288512
• 关键词: alcohols; aminosugar; antibiotics; drug design /synthesis /production; ethers; nuclear magnetic resonance spectroscopy; stereochemistry

The purpose of this study is to develop a general synthetic approach to a class of aminosugar antibiotics which include furanomycin, polyoxin J, miharamycin B, and lincomycin. The unifying structural feature of these compounds consists of either an erythro or threo disposed vicinal amino alkoxide moiety. Methodology will be explored which allows for the construction of such systems in chiral form with emphasis on acyclic stereocontrol. Towards this end, the use of chelation-controlled additions to chiral aldehydes and 1,3-dipolar cycloadditions involving a chiral nitrone will be investigated. The stereochemical course of these processes may be ascertained using high field NMR spectroscopy and/or chemical correlation with known systems. Should our predictions hold true, these results would be applicable to variety of synthetic endeavors. Thus, we hope to address the synthetic problems associated with these systems and apply the results to the preparation of medicinally and agriculturally useful natural products.

本研究的目的是开发一种通用的合成方法， 一类氨基糖抗生素，包括呋喃霉素、多抗霉素J， 米哈霉素B和林可霉素。 它们的统一结构特征 化合物由邻位或苏位排列的邻位氨基组成 烷氧基部分。 将探索允许 以手性形式构建这种系统，重点是无环的 立体控制 为此，螯合控制添加剂的使用 手性醛和1，3-偶极环加成反应， 将对硝酮进行调查。 这些过程的立体化学过程 可以使用高场NMR光谱和/或化学方法来确定 与已知系统的相关性。 如果我们的预测是正确的， 结果将适用于各种合成努力。 因此我们 希望解决与这些系统相关的综合问题， 将结果应用于医药和农业的制备， 有用的天然产品。