Asymmetric Synthesis of Macrolide Antibiotics

大环内酯类抗生素的不对称合成

• 批准号: 6785496
• 负责人: JAMES L LEIGHTON
• 金额: $ 32.13万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6785496
• 关键词: carbonyl group; catalyst; drug design /synthesis /production; macrolide antibiotics; stereochemistry

DESCRIPTION (provided by applicant): This proposal details the development of new, catalytic reaction methodology for the efficient asymmetric synthesis of polyacetate- and polypropionate-derived macrolide antibiotics, It has been documented that drug-resistant bacterial and fungal infections represent a problem of rapidly growing importance. More than simply achieving syntheses of such compounds, the focus of the proposal is on advancing the frontiers of efficiency, waste-minimization and economic viability of such synthetic efforts. The ultimate goal is thus the realization of practicable and practical chemistry that will affect both the discovery and process phases of research into new medicinal agents. This proposal addresses both the continuation and further development of the most promising discoveries made in the previous funding period, as well as exciting new directions only recently initiated. The reactions under study have as their unifying theme tandem reaction methodology. Tandem reactions are inherently more efficient as multiple chemical transformations may be accomplished, and multiple stereogenic centers may be established in a single operation. In this fashion, large segments of the target natural products may be synthesized with unprecedented efficiency employing only readily available and environmentally benign reagents.

描述（由申请人提供）：该提案详细介绍了用于有效不对称合成聚乙酸酯和聚丙酸酯衍生的大环内酯抗生素的新型催化反应方法的开发。据记载，耐药细菌和真菌感染是一个快速发展的问题。日益重要。该提案的重点不仅仅是实现此类化合物的合成，还在于推进此类合成工作的效率、废物最小化和经济可行性的前沿。因此，最终目标是实现实用化学，这将影响新药物研究的发现和过程阶段。 该提案涉及上一个资助期间最有希望的发现的延续和进一步发展，以及最近才启动的令人兴奋的新方向。所研究的反应以串联反应方法为统一主题。串联反应本质上更有效，因为可以完成多个化学转化，并且可以在单个操作中建立多个立体中心。以这种方式，仅使用容易获得且环境友好的试剂就可以以前所未有的效率合成大部分目标天然产物。