A PRACTICAL SYNTHETIC ROUTE TO THE TETRACYCLINES

四环素类药物的实用合成路线

• 批准号: 6626402
• 负责人: ANDREW G MYERS
• 金额: $ 24.45万
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626402
• 关键词: Diels Alder reaction; antibiotics; antineoplastic antibiotics; benzoates; benzofurans; chemical addition; chemical structure function; combinatorial chemistry; cyclohexanones; drug design /synthesis /production; drug resistance; intermolecular interaction; molecular shape; p aminobenzoate; palladium; stereochemistry; stereoisomer; tetracyclines

DESCRIPTION: (Principal Investigator's Abstract) The objective of this proposal is to develop the first practical, efficient, and enantioselective laboratory synthetic route(s) to the tetracycline antibiotics. The goal is to devise a route of twelve or fewer synthetic steps, perhaps as few as eight steps, beginning with benzoic acid as a starting material. A constraint that the synthetic route be versatile is also imposed, allowing for the introduction of substantive structural variability at a late stage, particularly within the C and D rings of the tetracycline structure, where prior research has shown that there is great opportunity for antibiotic development. Synthesis of a wide range of new tetracyclines for evaluation as improved antibiotics and, potentially antitumor agents is proposed. A particular focus is the development of effective antibiotics against tetracycline-resistant microorganisms. Adaptation and/or modification of these synthetic routes to target new tetracycline structures with antitumor activity, such as SF-2575 (TAN-1518 X) will also be attempted.

描述：（主要研究者的摘要）本提案的目标 是开发第一个实用、高效、对映选择性实验室 四环素抗生素的合成路线。目标是设计一个 十二个或更少的合成步骤的路线，也许少至八个步骤， 以苯甲酸作为起始材料开始。一个约束条件是 还强加了合成路线的通用性，允许引入 后期阶段的实质性结构变化，特别是在 C 内部 和四环素结构的 D 环，先前的研究表明 抗生素的发展蕴藏着巨大的机遇。合成宽 一系列新的四环素作为改进的抗生素进行评估， 提出了潜在的抗肿瘤药物。一个特别的重点是发展 针对四环素耐药微生物的有效抗生素。 调整和/或修改这些合成路线以瞄准新的目标 具有抗肿瘤活性的四环素结构，如SF-2575 (TAN-1518 X) 也将进行尝试。