Asymmetric Umpolung Aldehyde Reactions

不对称醛醛反应

• 批准号: 7120582
• 负责人: Tomislav Rovis
• 金额: $ 25.56万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-05 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120582
• 关键词: acetylcholine; aldehydes; angiogenesis inhibitors; antineoplastics; catalyst; chemical bond; chemical group; chemical reaction; chemical substitution; chemical synthesis; drug design /synthesis /production; method development; molecular polarity; neurotransmitter antagonist; nicotinic receptors; stereochemistry; stereoisomer

The proposed work outlines an investigation into the design of processes used to form congested, multiply substituted bonds by taking advantage of a functional group's reversal of polarity. The reactions under investigation will rely on the use of catalytic amounts of a chiral source. Once a foundation for the key reactivity has been laid, we will turn our attention of applying this research to the rapid and stereoselective synthesis of a number of biologically active targets. Azaspirene is a novel angiogenesis inhibitor, a potential target for anti-cancer agents. Asparagamine A is a potent nicotinic acetylcholine receptor antagonist. Its stereochemically dense, polycyclic structure provides an incentive for us to develop a better, more efficient approach to these molecules. Lastly, we hope to develop a general approach to controlling absolute stereochemistry in a subfield of reactions that utilize radicals to form new bonds. Accomplishing this feat would open new vistas in complex molecule assembly that could take advantage of the ability of radicals to sequence multiple chemical transformations in a single step.

拟议的工作概述了对利用官能团极性反转形成拥挤、多重取代键的工艺设计的研究。正在研究的反应将依赖于催化量的手性源的使用。一旦奠定了关键反应性的基础，我们将把注意力转向将这项研究应用于许多生物活性靶点的快速和立体选择性合成。 Azaspirene 是一种新型血管生成抑制剂，是抗癌药物的潜在靶点。 Asparagamine A 是一种有效的烟碱乙酰胆碱受体拮抗剂。其立体化学致密的多环结构激励我们开发更好、更有效的方法来研究这些分子。最后，我们希望开发一种通用方法来控制利用自由基形成新键的反应子领域中的绝对立体化学。完成这一壮举将为复杂分子组装开辟新的前景，可以利用自由基在一步中对多个化学转化进行排序的能力。