The Catalytic, Asymmetric Interrupted Feist-Benary Reaction

描述(申请人提供)：项目摘要：大多数用于治疗人类疾病的药物都是由人类制造或合成的，而不是从自然来源分离出来的。因此，不断开发新的反应来合成可能具有有益活性的类药物分子是非常重要的。这项建议描述了对一种特殊反应的调查，即“中断的”费斯特-比米勒(IFB)反应。这种反应产生一种特殊的分子结构，存在于许多分子中，这些分子有可能治疗真菌、细菌和病毒感染等疾病，以及某些形式的癌症。此外，IFB反应控制着这种分子结构的手性。手性是一种与分子的三维形状相关的性质，是决定分子如何与生物系统相互作用的基础。控制产物的手性也特别困难，但IFB反应非常有效地实现了这一点，从而创建了类似药物的分子结构。该提案描述了了解IFB反应如何控制产品手性的计划，测试该反应可以产生的各种产品的范围，以及将该反应用于合成三个具有生物活性和潜在临床活性的分子家族。相关性：本提案描述了几个潜在的抗真菌、抗生素、抗病毒和抗癌药物家族的合成。开发具有所有这些活性的新药物是至关重要的，因为真菌、细菌和病毒都对现有药物产生了抗药性，而现有的抗癌药物活性有限，副作用大。

DESCRIPTION (provided by applicant): Project Summary: Most of the drugs used to treat the diseases plaguing mankind are made, or synthesized, by humans, rather than being isolated from natural source. Therefore, it is very important to keep developing new reactions for synthesizing "drug-like" molecules, likely to have beneficial activity. This proposal describes an investigation of one particular reaction, the "interrupted" Feist-Benary (IFB) reaction. This reaction generates a specific molecular structure present in a number of molecules that have the potential to treat such conditions as fungal, bacterial and viral infections, along with some forms of cancer. Furthermore, the IFB reaction controls the chirality of this molecular structure. Chirality is a property associated with the three-dimensional shape of a molecule and is fundamental in determining how a molecule interacts with a biological system. It is also particularly difficult to control the chirality of a product, but the IFB reaction very effectively does this for the creation of the drug-like molecular structure. The proposal describes plans for understanding how the IFB reaction controls the chirality of the product, for testing how wide a variety of products the reaction can produce, and for using the reaction in the synthesis of three families of biologically active, potentially clinically active molecules. Relevance: This proposal describes the synthesis of several families of potential antifungal, antibiotic, antiviral, and anticancer agents. It is essential to develop new agents with all these activities, as fungi, bacteria and viruses are all developing resistance to existing drugs, and the existing anticancer agents have limited activity and potent side-effects.