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

项目摘要/摘要 快速和可靠地获取合成衍生的化学结构在许多方面都起着至关重要的作用 生物医学研究。家长奖的基本目标是从根本上提供新的 高度选择性的键形成战略，将使更快和更有效地获得生物 具有潜在治疗价值的活性化合物。使用小分子过渡金属催化剂， 将讨论烯烃和炔烃等简单结构亚基的区域选择性衍生化。 通过仔细的机制分析，将提供新的见解来指导实现这一目标的一般策略 在广泛的背景下实现这一目标。利用工程生物催化剂，将开发出战略，以 使用一种新的衬底工程，实现复杂衬底中C-H键的区域选择性氧化 一种将细胞色素P450介导的氧化反应引向嵌入在 复杂的分子骨架。该研究计划的目标将为以下方面提供高效的战略 影响和增强复杂结构的生物特性。生物医学领域的改进条目 这项研究使重要的结构成为可能，将使它们具有生物学功能和治疗作用 有可能被更有效地研究。本补充申请要求提供购买汽油的资金 色质联用(GCMS)仪器。这一工具将极大地增加 对上述项目进行分析的准确性和速度。这些改进将 实现新的发现，并将提高我们集团员工的生产力和效率 家长奖。

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.