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

说明（申请人提供）：用于治疗人类疾病的药物大多数是由人类制造或合成的，而不是从天然来源中分离出来的。因此，不断开发新的反应来合成可能具有有益活性的“药物样”分子是非常重要的。该提议描述了一系列反应的研究，所有反应都与一个特定的反应有关，即“中断”Feist-Benary（IFB）反应。这些反应产生存在于许多分子中的分子结构，这些分子具有治疗真菌、细菌和病毒感染以及沿着某些形式的癌症的潜力。此外，这些反应控制这些分子结构的手性。手性是与分子的三维形状相关的性质，并且是确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实现了这一点，以产生药物样分子结构。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产物的种类有多广，以及用于合成几个具有生物活性和潜在临床活性的分子家族的反应。 公共卫生相关性：该提案描述了几个潜在的抗真菌剂、抗生素、抗病毒剂和抗癌剂家族的合成。开发具有所有这些活性的新药剂是至关重要的，因为真菌、细菌和病毒都对现有药物产生了耐药性，而现有的抗癌药剂活性有限且副作用大。

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.