Asymmetric C-C Bond-Forming Reactions Catalyzed by Cinchona Alkaloid Derivatives

描述（由申请人提供）：用于治疗困扰人类的疾病的大多数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。本提案描述了一系列反应的研究，所有这些反应都与一个特定的反应有关，即“中断”的Feist-Benary （IFB）反应。这些反应产生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，这些反应控制了这些分子结构的手性。手性是一种与分子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和相关反应非常有效地控制了药物样分子结构的产生。该提案描述了发现新反应的计划，用于测试反应可以产生的各种产品的范围，以及将这些反应用于合成几个具有生物活性和潜在临床活性的分子家族。

DESCRIPTION (provided by applicant): 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 a series of reactions, all related to one particular reaction, the "interrupted" Feist-Benary (IFB) reaction. These reactions generate molecular structures 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, these reactions control the chirality of these molecular structures. 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 and related reactions very effectively do this for the creation of the drug-like molecular structures. The proposal describes plans for discovering new reactions, for testing how wide a variety of products the reactions can produce, and for using the reactions in the synthesis of several families of biologically active, potentially clincally active molecules. PUBLIC HEALTH 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.