Development of Strategies for the Synthesis of Heterocycles

项目概要/摘要 杂环化合物是人体必需的药物的普遍存在的组分， 健康制备含氮杂环的特别有吸引力的方法是 通过C-H键官能化改性廉价且容易获得的胺。 然而，有效完成此任务的方法通常需要使用 昂贵的过渡金属催化剂和/或氧化剂。该提案的重点是 设计和开发有效和实用的胺官能化方法， 包括不对称变体的开发。主要目标是阿尔法- 通过概念上新的和不发达的方法使胺官能化， 底物活化还将介绍合成杂环的独特方法。 在不对称刘易斯和布朗斯台德酸催化的背景下探索。除了 靶向快速制备与具有已知生物活性的结构相关的化合物， 活动，努力将集中在发展特别强大的反应， 快速产生新的多环杂环。一个优先事项是新一代 这些结构框架是当前药物发现筛选文库中所不存在的。

Project Summary/Abstract Heterocycles are ubiquitous components of pharmaceutical drugs essential for human health. A particularly attractive approach to nitrogen containing heterocycles is the modification of cheap and readily available amines via C–H bond functionalization. However, methods that efficiently accomplish this task typically require the use of expensive transition metal catalysts and/or oxidants. This proposal is focused on the design and development of efficient and practical methods for amine functionalization, including the development of asymmetric variants. The main goal is the alpha- functionalization of amines through conceptually new and underdeveloped methods of substrate activation. Unique methods for the synthesis of heterocycles will also be explored in the context of asymmetric Lewis and BrØnsted acid catalysis. In addition to targeting the rapid preparation of compounds related to structures with known biological activities, efforts will center on the development of particularly powerful reactions that rapidly produce new polycyclic heterocycles. A priority is the generation of new structural frameworks that are absent from current drug discovery screening libraries.