A NEW LEWIS ACID CATALYZED CLAISEN REARRANGEMENT

一种新的路易斯酸催化的克莱森重排

• 批准号: 6636597
• 负责人: David W MacMillan
• 金额: $ 17.83万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6636597
• 关键词: catalyst; chemical synthesis; molecular rearrangement; stereochemistry

DESCRIPTION: (Principal Investigator's Abstract) The objective of this research proposal is to invent catalytic synthetic methods that allow enantioselective access to structural and stereochemical motifs, which although common among anti-viral, anti-cancer, anti-bacterial and anti-inflammatory medicinal agents, connot be readily accessed using conventional methods. In this endeavor, we target processes that are readily applied within the related discipline of enantioselective catalysis and therefore will have a direct and immediate impact on the production of single enantiomer drugs with established biological importance. Our intent is to develop synthetic methods of broad utility and function that will ultimately provide new chemical tools for the diverse range of biomedical researchers that utilize molecule construction. As a consequence, this core research will prove valuable to a number of wide-ranging therapeutical areas. One of the most powerful tools for carbon-carbon bond formation in organic synthesis is the Claisen (3,3)-sigmatropic rearrangement. Remarkably, however, an enantioselective catalytic variant of this reaction has yet to be developed. This proposal outlines a new Lewis acid catalyzed Claisen rearrangement that is amenable to enantioselective catalysis and therefore the construction and modification of a diverse range of biologically important molecules and targets. The strategy is predicated on a new Lewis acid catalyzed Claisen rearrangement recently developed in our laboratory. We have already successfully demonstrated that this catalytic methodology is applicable to the construction of an unusually diverse spectrum of structural motifs. A major goal of this research is to utilize this powerful carbon-carbon bond forming methodology to expedite the synthesis of complex targets with important biological activity. One such example is the proposed general strategy towards the total syntheses of the briaranes, a marine metabolite family with extensive medicinal potential that have yet to be accessed through synthetic construction. This proposal outlines a new Lewis acid catalyzed tandem acyl-Claisen rearrangement that is broadly useful for the rapid construction of molecular complexity from simple reagents. This work will develop an innovative strategy for the one-step synthesis of stereochemically complex acyclic frameworks based upon a new tandem-Claisen reaction sequence. Having demonstrated the feasibility of this transformation, we hope to determine the scope and limitations of this catalytic tandem reaction methodology for the production of a range of functional, stereochemical and structural motifs. This methodology will be used in conjunction with our acyl-Claisen reaction for the highly expeditious synthesis of erythronolide B; a member of the erythromycin antibiotic class. This new chemical tool should prove valuable for the rapid construction of erythronolide analogues; an important area of research for treatment of resistant bacterial strains.

描述：(主要调查人员摘要)本研究的目的 建议发明催化合成方法，允许对映体选择性 获得结构和立体化学基序，尽管这些基序在 抗病毒、抗癌、抗菌、消炎药物， 不能使用常规方法容易地访问。在这一努力中，我们 在以下相关规程中容易应用的目标流程 因此对映体选择性催化会有直接和即时的 生物制剂对单一对映体药物生产的影响 重要性。我们的目标是开发具有广泛实用性的合成方法和 最终将为多样化的范围提供新的化学工具的功能 利用分子结构的生物医学研究人员。因此， 这一核心研究将被证明对许多广泛的 治疗领域。 有机碳-碳键形成最有力的工具之一 合成过程为Claisen(3，3)-Sigmatrotic重排反应。然而，值得注意的是， 该反应的对映选择性催化变体尚未开发出来。 该提案概述了一种新的路易斯酸催化的克莱森重排反应，即 服从对映体选择性催化，因此结构和 一系列生物重要分子的修饰和 目标。该策略是基于一种新的Lewis酸催化的Claisen 重排是我们实验室最近发展起来的。我们已经这么做了 成功地证明了这种催化方法适用于 构建了一个异常多样化的结构主题谱。一位少校 这项研究的目标是利用这种强大的碳-碳键形成 加速合成具有重要意义的复杂目标的方法学 生物活性。一个这样的例子是拟议的实现 具有广泛应用前景的海洋代谢物布里烷类化合物的全合成 尚未通过人工合成获得的药用潜力 建筑。 该方案概述了一种新的路易斯酸催化的串联酰基-克莱森 重排，广泛用于快速构建分子 简单试剂带来的复杂性。这项工作将制定一项创新的战略 一步法合成具有立体化学结构的无环骨架 建立了一个新的串联克莱森反应序列。在展示了 这种改造的可行性，我们希望确定范围和 这种催化串联反应方法在生产苯系物方面的局限性 一系列功能、立体化学和结构主题。这种方法论 将与我们的酰基-克莱森反应一起用于高度 红霉素中的一员赤藓内酯B的快速合成 抗生素课。这种新的化学工具应该被证明对快速 赤藓内酯类似物的构建；研究的一个重要领域 耐药菌株的治疗。