A NEW LEWIS ACID CATALYZED CLAISEN REARRANGEMENT

描述：（主要研究者摘要）本研究的目的 建议是发明催化合成方法， 获得结构和立体化学基序，虽然在 抗病毒、抗癌、抗菌和抗炎药剂， 使用常规方法不能容易地访问。在这奋进，我们 在相关学科中容易应用的目标过程， 对映选择性催化，因此将具有直接和立即的 对已建立生物制剂的单一对映体药物生产的影响 重要性我们的目的是开发具有广泛用途的合成方法， 功能，最终将提供新的化学工具， 生物医学研究人员利用分子结构。因此，在这方面， 这项核心研究将证明对许多广泛的 治疗领域。 有机碳中碳-碳键形成最有力的工具之一 合成是Claisen（3，3）-σ转移重排。然而，值得注意的是， 该反应的对映选择性催化变体还有待开发。 该提议概述了一种新的刘易斯酸催化的Claisen重排， 适合于对映选择性催化，因此构建和 修饰多种生物学重要分子， 目标的该策略基于一种新的刘易斯酸催化的Claisen 最近在我们实验室开发的重组。我们已经 成功地证明了这种催化方法适用于 构建了一个异常多样的结构基序谱。一个主要 这项研究的目的是利用这种强大的碳-碳键形成 加速综合复杂目标的方法， 生物活性其中一个例子是拟议的总战略， 全合成的briarane，一个海洋代谢物家族，具有广泛的 尚未通过合成药物获得的药用潜力 建设 该建议概述了一种新的刘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 从简单的试剂到复杂的试剂这项工作将制定一项创新战略 用于一步合成立体化学上复杂的基于 一个新的串联克莱森反应序列在展示了 我们希望确定这种转型的范围和可行性， 该催化串联反应方法用于生产 一系列功能性、立体化学和结构基序。这种方法 将与我们的酰基-克莱森反应结合使用， 红霉素B的快速合成;红霉素的一种 抗生素类这种新的化学工具应该证明是有价值的快速 的建设，一个重要的研究领域， 耐药菌株的治疗。

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.