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， 否则无法进行研究和评估的结构。我们的首要关注点 工作重点是新型四环素抗生素的合成和评价。为此，我们将 制备了各种具有修饰 C 和 D 环的 6-脱氧四环素，包括 杂环和稠环取代基（例如五环素）。我们现有的路线 6- 脱氧四环素将得到完善和规模化，目标是开发一条能够 提供克至公斤的新型合成四环素。更高效的 AB 构造 将探索四环素前体，以及 AB 和 D 环前体的聚合偶联 再次对四环素类ABCD环体系进行优化，以期开发出 可扩展、更高效的合成路线。此外，我们还将开展基础研究，探索 生产新型抗生素（称为“抗生素”）的新大环化路线的可行性 吡咯啶类药物。