Enantioselective Zwitterionic Reactions

新合成方法的设计对生物医学研究具有广泛的影响。在选择一种化合物作为潜在候选药物的过程中涉及许多因素，但其中一个至关重要但并不总是明确的因素是潜在靶点是否可达。如果一种化合物不能以实际的方式通过合成或从生物来源获得，那么它永远不会成为一种可行的药物制剂。因此，真正强大和前所未有的合成方法可以开辟新的结构支架的前景，作为潜在的药物靶点进行探索。这项研究计划的中心目标是开发新的战略反应，将在有机合成中产生广泛的影响。铑稳定的类碳化合物含有供体和受体基团，能够进行一系列合成上有用的转化。本文提出了一个新的研究方向，即铑结合两性离子中间体的对映选择性转化。这些新的合成方法的全部范围将被探索，然后应用于生物相关的天然产物和重要的药物支架的合成。

DESCRIPTION (provided by applicant): Research Summary The design of new synthetic methods has a broad impact on biomedical research. Many factors are involved in the selection of a compound as a potential drug candidate, but one that is critical, but not always articulated, is whether or not a potential target is accessible. If a compound cannot be made in a practical way either through synthesis or from biological sources, then it will never become a viable pharmaceutical agent. Consequently, truly powerful and previously unprecedented synthetic methods can open up vistas of novel structural scaffolds for exploration as potential drug targets. The central goal of this research program is to develop new strategic reactions that will have broad impact in organic synthesis. Rhodium-stabilized carbenoids containing both donor and acceptor groups are capable of a range of synthetically useful transformations. This proposal focuses on a new direction of study of donor/acceptor carbenoids, namely enantioselective transformations of rhodium-bound zwitterionic intermediates. The full scope of these new synthetic methods will be explored and then applied to the synthesis of biologically relevant natural products and important pharmaceutical drug scaffolds.