Biomimetics

仿生学

• 批准号: 6812634
• 负责人: Jeffrey Aube
• 金额: $ 12.26万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6812634
• 关键词: aminosugar; biomimetics; chemical addition; chemical structure; combinatorial chemistry; conformation; high throughput technology; nucleosides; piperidine; stereochemistry; technology /technique development

The main objective of this project is the development of new chemistry for preparing combinatorial libraries of biomimetics--compounds that mimic the building blocks of life such as amino acids, nucleosides, or carbohydrates. The key theme of this project will be the development of new methods for the combinatorial synthesis of scaffold-diverse libraries. In addition, the combinatorial libraries targeted within this project will incorporate pharmacophoric diversity while retaining critical drug-like features that will maximize the utility of these libraries in downstream biomedical applications. The overall goals of this project will be to (1) develop multicomponent reactions that provide for easy incorporation of peripheral diversity into biomedically important scaffolds, (2) develop methods that allow for the synthesis of diverse scaffold types within a single library, (3) emphasize control of stereochemistry and conformational diversity in library synthesis. These goals will be addressed through four specific aims, including (1) the development of a new three-component ring-expansion reaction, and (2) the investigation of a tandem Lewis acid promoted cycloaddition/intramolecular Schmidt reaction for combinatorial chemistry. In a second subproject, (3) the stereoselective synthesis of a unique class of C-5' modified nucleoside libraries and (4) the stereoselective synthesis of novel azasugar and polysubstituted piperidine libraries will be examined.

该项目的主要目标是开发新的化学方法，用于制备仿生学组合文库，这些化合物可以模拟生命的基本组成部分，如氨基酸、核苷或碳水化合物。该项目的关键主题将是开发新的方法来组合合成不同支架的文库。此外，该项目的组合文库将结合药效多样性，同时保留关键的药物样特征，这将最大限度地提高这些文库在下游生物医学应用中的效用。该项目的总体目标将是：(1)开发多组分反应，以便将外周多样性轻松整合到生物医学上重要的支架中；(2)开发允许在单个文库中合成多种支架类型的方法；(3)强调文库合成中立体化学和构象多样性的控制。这些目标将通过四个具体目标来实现，包括：(1)开发新的三组分环扩张反应，以及(2)研究串联Lewis酸促进的环加成/分子内施密特反应用于组合化学。在第二个子项目中，将研究(3)一类独特的C-5'修饰核苷库的立体选择性合成和(4)新型氮扎糖和多取代哌啶库的立体选择性合成。