Enantioselective Zwitterionic Reactions

对映选择性两性离子反应

• 批准号: 8471124
• 负责人: HUW M DAVIES
• 金额: $ 27.97万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471124
• 关键词: Academia; Alcohols; Alkenes; Binding; Biological; Biological Factors; Biomedical Research; Chemicals; Chemistry; Communities; Cyclopropanes; DNA Sequence Rearrangement; Development; Drug Industry; Drug Targeting; Electrons; Environment; Ethers; Goals; Indoles; Lead; Methodology; Methods; Organic Synthesis; Pharmaceutical Preparations; Pharmacologic Substance; Postdoctoral Fellow; Pyrroles; Reaction; Research; Rhodium; Scheme; Series; Source; System; Training; career; catalyst; coping; cycloaddition; cyclopropane; design; drug candidate; enol; graduate student; improved; interest; novel; programs; propadiene; scaffold; ylide

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.

描述（由申请人提供）：研究概述新合成方法的设计对生物医学研究具有广泛的影响。在选择化合物作为潜在候选药物时涉及许多因素，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获得。如果一种化合物不能通过合成或从生物来源以实用的方式制备，那么它将永远不会成为可行的药剂。因此，真正强大的和前所未有的合成方法可以开辟新的结构支架作为潜在的药物靶点的探索前景。该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。含有供体和受体基团的铑稳定的类卡宾能够进行一系列合成有用的转化。这一建议的重点是一个新的研究方向的供体/受体类卡宾，即对映体选择性转换铑结合的两性离子中间体。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。