Synthesis Based Upon Reactions of Oxocarbenium Ions

描述（由申请人提供）：尽管许多合成和生物转化涉及氧碳正离子中间体，但有关这些高反应性物质的结构和反应性的详细信息仍然未知。例如，关于甘露糖基阳离子的优选构象的争论仍在继续，尽管靶向这种阳离子的药物已经被测试用于治疗遗传和病毒性疾病以及癌症。在其他情况下，文献中仍然存在不一致之处，例如立体选择性糖基化中的邻位辅助的性质。该提案建立在我们在上一个资助期间的工作基础上，该工作证明了杂原子取代基对oxocarbenium离子构象的影响，从而影响了其反应的立体选择性。我们已经设计了一种方法来解决甘露糖基阳离子的结构，我们将深入了解的性质，邻位辅助。我们还设计了新的立体选择性合成方法的基础上oxocarbenium，peroxocarbenium，和iminium离子中间体。介绍了天然产物合成中的应用。 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设计。此外，我们对这些中间体的结构和反应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, peroxocarbenium, and iminium ion intermediates. Applications in natural product synthesis are described. 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.