Stereospecific cross-coupling reactions as a tool for three-dimensional molecular diversification

立体特异性交叉偶联反应作为三维分子多样化的工具

• 批准号: 10163211
• 负责人: Mark Roger Biscoe
• 金额: $ 30.72万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163211
• 关键词: 3-Dimensional; Architecture; Biological; Biological Assay; Carbon; Chemicals; Coupling; Data Analyses; Development; Libraries; Ligands; Methods; Modeling; Modernization; Molecular; Molecular Structure; Optics; Palladium; Pharmacologic Substance; Preparation; Principal Investigator; Reaction; Research; Structure; Techniques; Testing; Variant; Work; drug candidate; drug discovery; enantiomer; interest; novel therapeutics; programs; tool

PROJECT SUMMARY/ABSTRACT Using enantioenriched organometallic nucleophiles in palladium-catalyzed carbon-carbon bond- forming reactions, we aim to develop general tools for the rapid preparation of non-racemic biologically active molecules. By establishing the final stereogenic configuration prior to the formation of the final desired bond, the rapid preparation of diverse libraries of single- enantiomer drug candidates for use in biological assays will be achievable. The use of optically active secondary alkylboron and alkylstannane nucleophiles will initially be explored in Pd- catalyzed alkyl-aryl cross-coupling reactions, with particular focus on the derivatization of medicinally relevant organic frameworks. The inclusion of heterocycles will be emphasized in order to maximize access to chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest.

项目总结/摘要 在钯催化的碳-碳键- 形成反应，我们的目标是开发通用工具，用于快速制备非外消旋 生物活性分子。通过建立最终的立体构型之前， 形成最终所需的键，快速制备不同的单链抗体库， 用于生物测定的对映异构体药物候选物将是可实现的。使用光学 活性的仲烷基硼和烷基锡烷亲核试剂将首先在Pd- 催化的烷基-芳基交叉偶联反应，特别关注 医学相关的有机框架。杂环的包含将在下文中强调。 为了最大限度地获得手性结构基序， 生物学或药学兴趣。