COMBINATORIAL DETERMINATION OF ISOTOPE EFFECTS

描述：PI最近发现了一种高精度 天然丰度下小同位素效应的组合测定。 与测量同位素效应的传统方法相比， 该方法快1-2个数量级，通用性更强， 提供了更多的信息，并且更加可靠准确。 基于 这一发现，在这里提出研究一系列的机制， 重要的有机和生物有机反应。 其中包括 TMSCl介导的铜酸盐对烯酮的加成，Sharpless不对称 二羟基化，臭氧分解，角鲨烯氧化物的酶促环化， 烯反应和许多其他反应。 方法论的独特能力 应该能大大推进对这些反应的机理理解。 这项工作的健康相关性源于其对健康的影响。 对药物合成中重要反应的理解 重要的物质，以及生物合成中重要的反应 途径。 另一个目标是将该方法扩展到 确定结合同位素效应。 详细分析影响 对色谱分离的小同位素效应表明， 超高精度的测定应该是可能的NMR分析后， 色谱分离 获得的精确同位素效应应 提供了大量关于分子-分子或分子-表面的信息 交互. 目标是为一般性研究制定实用的方法， 结合同位素效应的研究，并发展这种方法在 研究分子间的相互作用。

DESCRIPTION: The PI has recently discovered a method for the high precision combinatorial determination of small isotope effects at natural abundance. Compared to conventional methods for measuring isotope effects, the methodology is 1-2 orders of magnitude faster, is much more versatile, provides much greater information, and is more reliably accurate. Based on this discovery it is proposed here to study the mechanisms of a series of important organic and bioorganic reactions. These include the TMSCl-mediated addition of cuprates to enones, the Sharpless asymmetric dihydroxylation, ozonolysis, the enzymatic cyclization of squalene oxide, ene reactions and many others. The unique capabilities of the methodology should significantly advance mechanistic understanding of these reactions. The health-relatedness of this work derives from its impact on the understanding of reactions important in the synthesis of medicinally important substances, and reactions centrally important in biosynthetic pathways. Another objective is to extend the methodology to the determination of binding isotope effects. A detailed analysis of the impact of small isotope effects on chromatographic separations suggests that their ultra-high precision determination should be possible by NMR analysis after chromatographic separation. The precise isotope effects obtained should provide tremendous information on molecule-molecule or molecule-surface interactions. The goal is to develop practical methodology for the general study of binding isotope effects, and develop the use of this methodology in studying molecule-molecule binding interactions.