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

项目总结/摘要 快速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提供全新的 高选择性键合形成的策略，这将使生物更快速，更有效地获得 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， 将阐述简单结构亚单元如烯烃和炔烃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，以指导一般战略， 在广泛的背景下客观。使用工程生物催化剂，将制定战略， 使用新型底物工程，能够在复杂底物中区域选择性氧化C-H键， 一种将细胞色素P450介导的氧化作用导向嵌入在细胞内的所需C-H键的方法， 复杂的分子结构。这项研究计划的目标将提供高度有效的战略， 影响和增强复杂结构的生物学特性。生物医学的改进条目 这项研究使重要的结构成为可能，将使它们的生物学功能和治疗 可以更有效地研究。此补充申请要求资金购买天然气 色谱-质谱（GCMS）仪器。这一工具将大大提高 对上述项目进行分析的准确性和速度。这些改进将 使新的发现，并将提高生产力和效率，我们的小组人员资助的 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.