Studies in the Synthesis of Physiologically Important

生理重要物质的合成研究

• 批准号: 6908180
• 负责人: JOHN L WOOD
• 金额: $ 32.95万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-17 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908180
• 关键词: Diels Alder reaction; alkyltransferase; antiinflammatory agents; biological products; calcium channel blockers; chemical synthesis; cyclic ketone; drug design /synthesis /production; drug screening /evaluation; insecticides; oxidation; oxidoreductase inhibitor; sorbitol; squalene

Efforts to prepare naturally occurring molecules of biological importance are extremely valuable to health sciences in the United States. Firstly, these efforts provide an exceptional training ground for scientist who will develop the next generation of important drugs. Second, these efforts always provide a unique means of accessing structure activity relationship data for the natural products themselves and compounds in similar structural classes. Thirdly, these efforts always result in the development of new strategies and chemistry that can be used for the synthesis of complex molecules. This proposal describes three such synthetic efforts. The most mature is directed toward a class of squalene synthase inhibitors known as the phomoidrides. Efforts in this area have spawned new chemistry in the field of aryl oxidation; further developments in this area are proposed along with a second synthetic effort directed toward ryanodol, an important calcium channel blocker. Finally, a fruitful collaborative effort looking at the biology of alpha, beta-epoxy ketone-containing natural products is described that is destined to provide important biological information about molecules in the sorbicillin class.

制备具有生物学重要性的天然分子的努力对于美国的健康科学极其有价值。 首先，这些努力为开发下一代重要药物的科学家提供了特殊的训练场地。 其次，这些努力始终提供了一种独特的方法来访问天然产物本身和类似结构类别的化合物的结构活性关系数据。 第三，这些努力总是导致可用于合成复杂分子的新策略和化学的发展。 该提案描述了三项此类综合工作。 最成熟的是针对一类被称为拟磷酰胺的角鲨烯合酶抑制剂。 这一领域的努力催生了芳基氧化领域的新化学；提出了该领域的进一步发展以及针对 ryanodol（一种重要的钙通道阻滞剂）的第二次合成努力。最后，描述了对含α，β-环氧酮的天然产物的生物学的富有成效的合作努力，这注定会提供有关山梨西林类分子的重要生物学信息。