Synthesis of Antibiotics

抗生素的合成

• 批准号: 7037200
• 负责人: ANDREW G MYERS
• 金额: $ 35.3万
• 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/7037200
• 关键词: antibiotics; benzoates; chemical addition; chemical structure function; cyclization; drug design /synthesis /production; multidrug resistance; pyrrolidinediones; stereochemistry; tetracyclines

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：该提案的统一目标是开发复杂抗生素的有效合成途径，否则将无法进行研究和评估。我们工作的主要重点是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环和D环的特别多种的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6-脱氧四环素路线将得到改进和扩大，目标是开发一种能够提供克至公斤新型合成四环素的路线。将探索AB四环素前体的更有效的构建，并且将优化AB和D-环前体的会聚偶联以得到四环素的ABCD环系统，再次着眼于开发可扩展的、更有效的合成路线。此外，我们将进行基础研究，探索一种新的大环化路线的可行性，以生产新的抗生素类被称为吡咯烷。