Synthesis of Antibiotics

抗生素的合成

• 批准号: 7538338
• 负责人: ANDREW G MYERS
• 金额: $ 31.24万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538338
• 关键词: Antibiotics; Applications Grants; Area; Benzoic Acids; Binding; Biological Factors; Complex; Coupling; Development; Evaluation; Evaluation Studies; Goals; Kilogram; Minocycline; Multi-Drug Resistance; Protocols documentation; Ribosomes; Route; Staging; Structure; Students; System; Tetracyclines; Work; novel; pyridine

The unifying goal of this proposal is to develop efficient synthetic routes to complex antibiotics, structures that would otherwise be inaccessible for study and evaluation. The primary focus of our work is on the synthesis and evaluation of novel tetracycline antibiotics. Toward this end, we will prepare an extraordinary variety of 6-deoxytetracyclines with modified C and D rings, including heterocycles and fused-ring substituents (e.g., pentacyclines). Our existing route to 6- deoxytetracyclines will be refined and scaled, with the goal of developing a route capable of providing grams to kilograms of novel synthetic tetracyclines. More efficient constructions of AB tetracycline precursors will be explored, and the convergent coupling of AB and D-ring precursors to give the ABCD ring system of the tetracyclines will be optimized, again, with a view to developing a scalable, more efficient synthetic route. In addition, we will undertake basic studies to explore the feasibility of a novel macropolycyclization route to produce the new class of antibiotics known as the pyrrocidines.

该提案的统一目标是开发复杂抗生素的有效合成路线， 这些结构否则将无法进行研究和评估。我们的主要重点是 工作是合成和评价新的四环素抗生素。为此，我们将 制备具有修饰的C和D环的特别种类的6-脱氧四环素，包括 杂环和稠环取代基（例如，五环素类）。我们现有的路线6- 脱氧四环素类药物将被精制和规模化，目标是开发一种能够 提供克至千克的新型合成四环素。AB的更有效构造 四环素前体将被探索，AB和D-环前体的会聚偶联， 给出了四环素类的ABCD环系统将被优化，再次，以期开发一种 可扩展的、更有效的合成路线。此外，我们会进行基础研究，探讨 一种新的大分子多环化路线的可行性，以生产新的抗生素，称为 吡咯烷类。