Metal-Catalyzed Cross-Coupling Reactions Using Optically-Active Nucleophiles

使用光学活性亲核试剂的金属催化交叉偶联反应

• 批准号: 8078467
• 负责人: Mark Roger Biscoe
• 金额: $ 13.87万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8078467
• 关键词: Architecture; Biological; Biological Assay; Carbon; Coupling; Data; Development; Goals; Hydrogenation; In Situ; Individual; Kinetics; Libraries; Ligands; Metals; Methods; Molecular; Optics; Organotin Compounds; Pharmacologic Substance; Preparation; Process; Reaction; Reagent; Research; Research Personnel; Route; Techniques; Testing; Transition Elements; Vinyl Compounds; Work; aryl halide; computer studies; drug candidate; drug discovery; enantiomer; interest; programs

DESCRIPTION (provided by applicant): We aim to develop new, general methods for obtaining non-racemic biologically-active molecules using transition metal-catalyzed carbon-carbon bond-forming reactions that employ configurationally-stable, optically-active nucleophiles. By establishing the stereogenic center prior to the formation of the final desired bond, the rapid preparation of diverse libraries of single-enantiomer drug candidates for use in biologic assays will be achievable. The use of optically-active secondary nucleophiles will be initially explored in alkyl-aryl cross-coupling reactions and extended to alkyl-alkyl cross-coupling reactions in order to maximize access to chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest. PUBLIC HEALTH RELEVANCE: Our proposed research focuses on the development of new, general methods to prepare diverse libraries of biologically-active molecules for testing as drug candidates. We aim to devise new drug discovery techniques that permit rapid access to common, high- demand molecular architectures predictably, safely, and inexpensively.

描述（由申请人提供）：我们的目标是开发使用过渡金属催化的碳-碳键形成反应获得非外消旋生物活性分子的新的通用方法，该反应采用构型稳定的光学活性亲核试剂。通过在形成最终所需键之前建立立体中心，将可实现用于生物测定的单一对映体候选药物的多种文库的快速制备。光学活性的二级亲核试剂的使用将首先在烷基-芳基交叉偶联反应中进行探索，并扩展到烷基-烷基交叉偶联反应，以最大限度地获得目前无法获得但具有生物学或药学意义的手性结构基序。 公共卫生相关性：我们建议的研究重点是开发新的通用方法，以制备各种生物活性分子库，用于作为候选药物进行测试。我们的目标是设计新的药物发现技术，允许快速获得共同的，高需求的分子结构可预测的，安全的，和廉价的。