COMBINATORIAL DETERMINATION OF ISOTOPE EFFECTS

描述：（主要研究者摘要）根据我们的持续研究， 发展强大而快速的反应研究方法 机制，我们建议研究一系列重要的机制 有机、有机金属和生物有机反应。其中包括缩窄 反应，共轭加成铜酸盐，烯烃复分解，加成 烯酮和膦酰亚胺转化为烯烃， 乳清酸，角鲨烯氧化物的酶促环化，以及许多其他方法。的 我们的方法的独特能力应该大大提高 对这些反应的机械理解。我们还计划扩大我们的 通过开发更强大的反应机制探针， 结构和分子间相互作用的同位素效应探针。的 这项工作的健康相关性源于其对理解的影响， 在合成药用重要物质中重要的反应， 生物合成途径中的重要反应。

DESCRIPTION: (Principal Investigator's Abstract) Based on our continued development of powerful and rapid methodology for the study of reaction mechanisms, we propose to study the mechanisms for a series of important organic, organometallic, and bioorganic reactions. This includes coarctate reactions, conjugate additions to cuprates, olefin metathesis, additions of ketenes and phosphinidenes to alkenes, the enzymatic decarboxylation of orotate, the enzymatic cyclization of squalene oxide, and many others. The unique capabilities of our methodologies should significantly advance mechanistic understanding of these reactions. We also plan to extend our methodology by developing more robust probes of reaction mechanisms and isotope-effect probes of structure and intermolecular interactions. 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 important in biosynthetic pathways.