Development of Strategies for the Synthesis of Heterocycles

杂环合成策略的发展

• 批准号: 10622971
• 负责人: Daniel Seidel
• 金额: $ 36.06万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622971
• 关键词: Acids; Amines; Biological; Catalysis; Complex; Development; Essential Drugs; Generations; Goals; Health; Human; Hydrogen Bonding; Libraries; Methods; Modification; Molecular Structure; Nitrogen; Oxidants; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Reaction; Structure; Techniques; Transition Elements; Variant; catalyst; cost efficient; design; drug discovery; public health relevance; screening

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.

项目概要/摘要 杂环化合物是人类必需的药物中普遍存在的成分 处理含氮杂环化合物的一个特别有吸引力的方法是 通过C-H键功能化对廉价且容易获得的胺进行改性。 然而，有效完成此任务的方法通常需要使用 该提案的重点是昂贵的过渡金属催化剂和/或氧化剂。 设计和开发有效且实用的胺官能化方法， 包括开发不对称变体，主要目标是α-。 通过概念上新的和尚未开发的方法对胺进行官能化 底物活化也将是杂环合成的独特方法。 在不对称路易斯和布朗斯台德酸催化的背景下进行了探索。 靶向快速制备与已知生物结构相关的化合物 活动、努力将集中于发展特别强大的反应， 快速产生新的多环杂环是首要任务。 当前药物发现筛选库中缺少的结构框架。