ALKOXYCARBINYL RADICALS IN ORGANIC SYNTHESIS

有机合成中的烷氧基羰基

• 批准号: 6342914
• 负责人: Randall L Halcomb
• 金额: $ 14.82万
• 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/6342914
• 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.

拟议的研究计划将基于 烷氧基甲苯基自由基，用于高度的不对称合成 氧化环和无环系统。 这些方法将被应用 为了合成天然产物，设计的生物探针和 酶抑制剂，因此在药用中有益 整个化学领域。 要解决的特定研究领域 包括：1。开发合成高充氧的新方法 使用烷氧基甲苯基自由基的桥接环系统。 这些方法会 应用于Zaragozic酸的总合成（Sopalestatin）。 现成的Zaragozic Acid环系统将允许设计 以及利用二磷酸酶的新型酶抑制剂的合成 包含底物。 2。开发合成的新方法 复杂的螺旋环系统，包括螺旋体和 基于烷氧基甲苯基自由基的螺旋体。 这些方法将是 应用于构象约束糖肽的合成 反过来，这对于探测糖蛋白结构和 在生物系统中的功能。 这些化合物尤其是 对涉及的生物过程的调查有用 碳水化合物识别。