ALKOXYCARBINYL RADICALS IN ORGANIC SYNTHESIS

有机合成中的烷氧基羰基

• 批准号: 6138507
• 负责人: Randall L Halcomb
• 金额: $ 14.4万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138507
• 关键词: biological products; chemical synthesis; enzyme inhibitors; free radicals; glycoprotein structure; stereochemistry

The proposed research program would develop methods, based on alkoxycarbinyl radicals, for the asymmetric synthesis of highly oxygenated cyclic and acyclic systems. These methods would be applied to the synthesis of natural products, designed biological probes, and enzyme inhibitors, and thus would be of benefit in the medicinal chemistry arena in general. Specific research areas to be addressed include: 1. Development of new methods to synthesize highly oxygenated bridged ring systems using alkoxycarbinyl radicals. These methods would be applied to the total synthesis of zaragozic acid (squalestatin). Ready access to the zaragozic acid ring system would allow the design and synthesis of novel inhibitors of enzymes that utilize diphosphate- containing substrates. 2. Development of new methods for the synthesis of complex spirocyclic ring systems, including spiroethers and spiroketals, based on alkoxycarbinyl radicals. These methods would be applied to the synthesis of conformationally constrained glycopeptides which, in turn, would be useful for probing glycoprotein structure and function in biological systems. These compounds would be particularly useful for investigations into biological processes involving carbohydrate recognition.

拟议的研究计划将开发方法，基于 烷氧基羰基自由基，用于高度不对称合成 含氧循环和非循环系统。 这些方法将被应用 天然产物的合成，设计的生物探针，以及 酶抑制剂，因此在医学上有好处 一般化学领域。 需要解决的具体研究领域 包括： 1. 开发合成高含氧化合物的新方法 使用烷氧基羰基的桥环系统。 这些方法将 应用于萨拉戈酸（squalestatin）的全合成。 方便地访问萨拉哥酸环系统将允许设计 以及利用二磷酸盐的新型酶抑制剂的合成 含有基材。 2. 合成新方法的开发 复杂的螺环系统，包括螺醚和 螺缩酮，基于烷氧基羰基。 这些方法将是 应用于构象受限糖肽的合成 反过来，这将有助于探测糖蛋白结构和 在生物系统中的功能。 这些化合物将特别 可用于研究涉及的生物过程 碳水化合物识别。