Stereoselective Synthesis Based upon Reactions of Oxocarbenium Ions

描述(申请人提供)：尽管许多合成和生物转化涉及氧碳正离子中间体，但关于这些高活性物种的结构和反应活性的细节仍不清楚。例如，关于甘露糖阳离子的首选构象的争论仍在继续，尽管针对这种阳离子的药物已经被测试用于治疗遗传和病毒疾病以及癌症。在其他情况下，文献中的不一致之处仍然存在，例如立体选择性糖基化中锚定辅助的性质。这项建议建立在我们在上一次资助期间的工作基础上，该工作证明了杂原子取代基对氧碳正离子构象的影响，从而证明了它们反应的立体选择性。我们设计了一种解决甘露糖阳离子结构的方法，我们将深入了解固定辅助的性质。我们还设计了基于氧卡宾和过氧卡宾离子中间体的新的立体选择性合成方法。 这项建议将对公众健康产生重大影响。例如，我们对碳水化合物衍生中间体的三维结构的研究将影响治疗糖尿病、肝炎、艾滋病毒和癌症的药物的设计。此外，我们对这些中间体的结构和反应活性的研究将使化学家能够更有效地制备这些药物。

DESCRIPTION (provided by applicant): Although many synthetic and biological transformations involve oxocarbenium ion intermediates, details about the structure and reactivity of these highly reactive species remain unknown. For example, debate continues about the preferred conformation of the mannosyl cation, although drugs targeting this cation have been tested to treat genetic and viral diseases as well as cancer. In other cases, inconsistencies in the literature remain, such as the nature of anchimeric assistance in stereoselective glycosylation. This proposal builds upon our work during the last funding period that demonstrates the influence of heteroatom substituents on the conformations of oxocarbenium ions and thus the stereoselectivity of their reactions. We have devised an approach to solving the structure of the mannosyl cation, and we will gain insight into the nature of anchimeric assistance. We have also devised new stereoselective synthetic methods based upon oxocarbenium and peroxocarbenium ion intermediates. This proposal will have considerable implications for public health. For example, our studies on the three- dimensional structures of carbohydrate-derived intermediates will impact the design of drugs for the treatment of diabetes, hepatitis, HIV, and cancer. In addition, our studies on the structure and reactivity of these intermediates will enable chemists to prepare those drugs more efficiently.