Enantioselective Zwitterionic Reactions

描述(申请人提供)：研究总结新合成方法的设计对生物医学研究有广泛的影响。选择一种化合物作为潜在的候选药物涉及许多因素，但关键但并不总是明确的一点是，潜在的靶点是否可用。如果一种化合物不能通过合成或生物来源以实用的方式制造，那么它永远不会成为一种可行的药剂。因此，真正有效和史无前例的合成方法可以为探索潜在的药物靶点开辟新的结构支架的前景。该研究计划的中心目标是开发将在有机合成中产生广泛影响的新的战略反应。同时含有给体和受体基团的铑稳定的卡宾类化合物能够进行一系列合成上有用的转化。这一建议着眼于给体/受体类卡宾的一个新的研究方向，即与Rh结合的两性离子中间体的对映选择性转化。探索这些新的合成方法的全部范围，然后应用于合成与生物相关的天然产物和重要的药物支架。 公共卫生相关性：更广泛的意义：这项研究计划旨在开发新的合成方法，广泛应用于天然产品和药物靶标的立体选择性合成的简化方案。与旨在改进已有反应的研究相比，这种方法可能会产生合成方法，这些方法可能会对改变合成中使用的策略类型产生重大影响。研究小组具有广泛的协作性，培训环境非常适合对制药行业或学术界职业感兴趣的研究生和博士后。

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. PUBLIC HEALTH RELEVANCE: Broader Significance: This research program is directed towards the development of new synthetic methods with broad application for streamlining schemes for the stereoselective synthesis of natural products and pharmaceutical targets. The approach is likely to generate synthetic methods that can have a major impact on changing the type of strategies that are used in synthesis compared to studies aimed at improving established reactions. The research group is broadly collaborative and the training environment is ideal for graduate students and post docs who are interested in careers in the pharmaceutical industry or academia.