Synthesis Based Upon Reactions of Oxocarbenium Ions

基于氧碳鎓离子反应的合成

• 批准号: 7617549
• 负责人: KEITH ALLEN WOERPEL
• 金额: $ 23.47万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617549
• 关键词: Address; Biological; Carbohydrates; Cations; Diabetes Mellitus; Diffusion; Drug Delivery Systems; Drug Design; Electronics; Evaluation; Funding; Genetic; HIV; Hepatitis; Investigation; Ions; Lactones; Literature; Malignant Neoplasms; Methods; Molecular Conformation; Nature; Pharmaceutical Preparations; Public Health; Reaction; Research; Structure; Testing; Virus Diseases; Work; base; glycosylation; insight; preference; reaction rate; three dimensional structure

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.

描述（由申请人提供）：尽管许多合成和生物学转化涉及氧化核离子中间体，但有关这些高度反应性物种的结构和反应性的详细信息仍然未知。例如，尽管已经测试了针对这种阳离子的药物以治疗遗传和病毒疾病以及癌症的癌基阳离子的首选构象的争论继续存在。在其他情况下，文献中的不一致仍然存在，例如立体选择性糖基化的固定辅助性质。该提议基于我们在最后一个资金期间的工作，证明了杂原子取代基对氧化核离子构象的影响，从而表明其反应的立体选择性。我们已经设计了一种解决甘露糖基阳离子结构的方法，我们将深入了解锚固援助的性质。我们还设计了基于氧碳和过氧化物离子中间体的新立体选择合成方法。 该提案将对公共卫生产生重大影响。例如，我们对碳水化合物衍生的中间体的三维结构的研究将影响用于治疗糖尿病，肝炎，HIV和癌症的药物。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准备这些药物。