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

金鸡纳生物碱衍生物催化的不对称 C-C 键形成反应

基本信息

批准号：
7981266
负责人：
Michael Arthur Calter
金额：
$ 47.25万
依托单位：
WESLEYAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-15 至 2015-01-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：大多数用于治疗困扰人类疾病的药物是由人类制造的或合成的，而不是与自然来源隔离。因此，继续开发新的反应以合成“像药物”分子，可能具有有益的活性。该提案描述了一系列反应的研究，这些反应与一种特定反应有关，即“中断” Feist-benary（IFB）反应。这些反应产生了许多分子中存在的分子结构，这些分子具有治疗真菌，细菌和病毒感染以及某些形式的癌症等疾病的潜力。此外，这些反应控制着这些分子结构的手性。手性是与分子的三维形状相关的特性，对于确定分子如何与生物系统相互作用至关重要。控制产品的手性也尤其困难，但是IFB和相关反应非常有效地为创建类似药物的分子结构而做到这一点。该提案描述了发现新反应的计划，用于测试反应可以产生多种产品的宽度，并在合成几个生物活性，潜在的活性分子的几个家族中使用反应。公共卫生相关性：该提案描述了几个潜在抗真菌，抗生素，抗病毒和抗癌药的综合。必须开发所有这些活动的新代理，因为真菌，细菌和病毒都在对现有药物产生抗性，并且现有的抗癌药物的活性有限和有效的副作用。