New Approaches to Catalyst Screening and Development

本项目将继续致力于开发使用酶作为分析传感器的催化剂筛选方法。 这种方法被称为原位酶筛选（ISES）。 虽然建立了色谱筛选方法，但这些方法通常作为系列时间点测定法运行，需要在分析前取出等分试样并进行后处理。 ISES方法提供了获得相对反应速率的并行的、真实的时间估计的可能性，并且在理想情况下，提供了对映体诱导的意义和大小的可能性，而不需要在底物中安装发色团或质量标签。 该项目下一个周期的一个关键目标是提高ISES筛选的通量，以便可以筛选更大的潜在催化组合矩阵。 同样重要的是进一步开发在上一个循环中发现的最有趣的催化剂，包括基于碳水化合物的手性salen配体，以及用于正式卤代碳环化过程的后过渡金属卤化物的新组合。 此外，还将进一步扩大通过ISES筛选的化学范围。有了这个奖项，有机和高分子化学计划将支持大卫教授B的研究。内布拉斯加大学化学系的Berkowitz说。 Berkowitz教授的研究工作包括开发有用的新催化剂，用于小环化合物的立体控制打开，以及碳-卤素和碳-碳键的形成。 该方法的成功开发将对学术界和工业界的合成产生影响，后者特别是在组合催化和制药工艺领域。

This project will continue work on the development of catalyst screening methods that employ enzymes as the analytical sensors. This approach has been labeled In Situ Enzymatic Screening (ISES). While chromatographic screening methods are established, these are normally run as serial, time point assays, requiring aliquot removal and work-up, prior to analysis. The ISES method offers the possibility to obtain parallel, real time estimates of relative reaction rates and, in ideal cases, sense and magnitude of enantio-induction, without the need to install a chromophore or mass tag in the substrate. A key goal of the next cycle of this project is to enhance the throughput of the ISES screening, such that larger matrices of potential catalytic combinations may be screened. Also important will be to further develop the most interesting catalysts uncovered in the last cycle, including carbohydrate-based chiral salen ligands, and new combinations of late transition metal halides for formal halocarbocyclization processes. In addition, further expansion of the scope of chemistry that is amenable to screening via ISES will be investigated.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor David B. Berkowitz in the Department of Chemistry at the University of Nebraska. Professor Berkowitz's research efforts include the development of useful new catalysts for the stereo-controlled opening of small ring compounds, and for carbon-halogen and carbon-carbon bond formation. Successful development of the methodology will have an impact on synthesis in both the academic and industrial communities, the latter particularly in the combinatorial catalysis and pharmaceutical process areas.