Supplement: Regio- and Site-Selective Processes Using Transition Metal and Biological Catalysts

补充：使用过渡金属和生物催化剂的区域和位点选择性过程

• 批准号: 9708114
• 负责人: JOHN MONTGOMERY
• 金额: $ 9.22万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9708114
• 关键词: Address; Alkenes; Alkynes; Award; Biological; Biological Process; Biological Response Modifier Therapy; Biomedical Research; Chemical Structure; Complex; Cytochrome P450; Engineering; Funding; Goals; Human Resources; Hydrogen Bonding; Mass Fragmentography; Mediating; Methods; Molecular; Parents; Play; Preparation; Process; Productivity; Property; Request for Applications; Research; Role; Site; Speed; Structure; Therapeutic; Transition Elements; catalyst; cost; improved; insight; instrument; interdisciplinary approach; novel; oxidation; programs; small molecule

Project Summary / Abstract Rapid and reliable access to synthetically-derived chemical structures plays an essential role in many aspects of biomedical research. The underlying objective of the parent award is to provide fundamentally new strategies for highly selective bond formations that will enable more rapid and efficient access to biologically active compounds of potential therapeutic value. Using small molecule transition metal catalysts, the regioselective derivatization of simple structural subunits such as alkenes and alkynes will be addressed. Through careful mechanistic analysis, new insights will be provided to guide general strategies toward this objective in a broad range of contexts. Using engineered biological catalysts, strategies will be developed to enable regioselective oxidations of C-H bonds in complex substrates, using a novel substrate engineering approach that directs cytochrome P450-mediated oxidations towards a desired C-H bond embedded within a complex molecular framework. The goals of this research program will provide highly effective strategies for impacting and enhancing the biological properties of complex structures. The improved entries to biomedically important structures made possible by this research will enable their biological function and therapeutic potential to be more efficiently studied. This supplement application requests funds for purchase of a Gas Chromatography – Mass Spectrometry (GCMS) instrument. This instrument will greatly increase both the accuracy and the speed of analyses conducted on the projects described above. These improvements will enable new discoveries and will increase productivity and efficiency of our group personnel funded on the parent award.

项目摘要 /摘要 快速可靠地获得合成的化学结构在许多方面起着至关重要的作用 生物医学研究。父母奖的基本目标是提供从根本上提供新的 高度选择性键形成的策略，这些策略将使生物学上更快，更有效地访问 潜在治疗价值的活性化合物。使用小分子过渡金属催化剂， 将解决简单结构亚基（例如烷烃和炔烃）的调节性衍生化。 通过仔细的机械分析，将提供新的见解来指导一般策略 在广泛的环境中的客观。使用工程化的生物催化剂，将制定策略 使用新型的底物工程启用复杂底物中C-H键的调节选择性氧化物 将细胞色素P450介导的氧化引向所需的C-H键的方法 复杂的分子框架。该研究计划的目标将为 影响和增强复杂结构的生物学特性。改进的生物医学条目 这项研究使重要结构成为可能的生物学功能和治疗 潜力更有效地研究。此补充申请要求购买天然气的资金 色谱 - 质谱（GCM）仪器。该乐器将大大增加 对上述项目进行的准确性和分析速度。这些改进将会 启用新发现，并将提高我们的团体人员的生产率和效率 父母奖。