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.

这项提案的统一目标是开发合成复杂抗生素的高效合成路线， 以其他方式无法进入进行研究和评估的结构。我们的主要重点是 工作是关于新型四环素类抗生素的合成和评价。为此，我们将 制备具有修饰的C和D环的特殊种类的6-脱氧四环素，包括 杂环和稠环取代基(如五环类)。我们现有的路线是6- 脱氧四环素将得到提炼和规模化，目标是开发一条能够 提供克到公斤的新型合成四环素。AB的更有效的构造 将探索四环素前体，以及AB和D环前体的收敛偶联 给出了ABCD环系对四环素类药物的再优化，以期开发出一种 可扩展、更高效的合成路线。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生产新型抗生素的可行性 吡咯西林。