Stereoselective 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羰基离子中间体，但这些高活性物质的结构和反应性的细节仍然未知。例如，尽管针对甘露糖基阳离子的药物已被测试用于治疗遗传和病毒疾病以及癌症，但关于甘露糖基阳离子的首选构象的争论仍在继续。在其他情况下，文献中的不一致仍然存在，例如在立体选择性糖基化中的嵌合辅助的性质。本提案建立在我们在上一个资助期的工作基础上，证明了杂原子取代基对氧羰基离子构象的影响，从而影响了它们的反应的立体选择性。我们已经设计了一种方法来解决甘露糖基阳离子的结构，我们将深入了解嵌合辅助的性质。我们还设计了新的基于氧羰基和过氧羰基离子中间体的立体选择性合成方法。

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.