Studies in the Synthesis of Physiologically Important

生理重要物质的合成研究

• 批准号: 6755957
• 负责人: JOHN L WOOD
• 金额: $ 33.09万
• 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/6755957
• 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.

准备天然生物学重要性分子的努力对美国的健康科学非常有价值。 首先，这些努力为科学家提供了卓越的培训理由，科学家将开发下一代重要的药物。 其次，这些努力始终提供了一种独特的手段，可以访问天然产品本身的结构活动关系数据以及类似结构类别的化合物。 第三，这些努力始终导致新策略和化学的发展，可用于合成复杂分子。 该提案描述了三个这样的综合努力。 最成熟的是针对一类称为phomoidrides的小矛烯合酶抑制剂。 该领域的努力在芳基氧化领域产生了新的化学。提出了这一领域的进一步发展，以及针对重要的钙通道阻滞剂Ryanodol的第二个合成努力。最后，描述了含有β-环氧酮的天然产物的生物学的一项富有成果的合作努力，注定要提供有关索比西林类中分子的重要生物学信息。