Asymmetric Ugi for a Diversity-Oriented Pathway

面向多样性的途径的不对称 Ugi

基本信息

批准号：
6881220
负责人：
Peter R Andreana
金额：
$ 1.72万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2005-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The identification of complex small molecules, which bind to receptors, proteins and enzymes, has been expedited through the use of combinatorial methods and the development of high throughput screening. The identified biological targets serve as powerful tools for pharmacological studies and are essential for drug development. The long term objectives of this proposed research are: to make creative contributions to the catalytic asymmetric synthesis of multicomponent coupling reactions namely the Ugi four component coupling reaction, to elucidate the general mechanism of the reaction, to develop a complex small molecule library incorporating appending processes, differentiating processes and folding processes so that from one reaction process, many different skeletal structures can be realized, and to determine the interaction that the range of compounds have on receptors, proteins and enzymes. Through the use of chiral Lewis acids, stereo-diversity will be incorporated into a tricyclic-lactam intermediate whereby building block diversity, through appending processes, will decorate this core structure. A metathesis reaction will reveal a folding process producing compounds with varying skeletal arrays. These complex small molecules will be utilized in a chemical genetics approach to perturb biological function through cytoblot assays and decipher disease pathways by utilizing the technique of high throughput screening. Both phenotypic screens and protein-binding assays will be performed to generate direct leads for drug development and cancer treatment.

描述（由申请人提供）：通过使用组合方法和高吞吐量筛选的发展，已经加快了与受体，蛋白质和酶结合的复杂小分子的鉴定。确定的生物学靶标是药理研究的强大工具，对于药物开发至关重要。这项拟议的研究的长期目标是：为催化不对称的不对称合成做出创造性的贡献，即UGI四组分耦合反应，以阐明反应的一般机制，以开发一个复杂的小分子库，从而结合了一个不同的小分子库，从而使附录过程和折叠过程构成了一个不同的构成过程，并且可以使许多不同的交易过程构成了许多不同的反应过程，并且可以实现许多不同的反应，并且可以实现许多不同的反应，并且可以使许多不同的交易过程，并且可以实现多个型号的反应。化合物的范围在受体，蛋白质和酶上。通过使用手性刘易斯酸，立体声多样性将被纳入三环 - 内酰胺中间体中，从而通过添加过程来装饰这种核心结构。复合反应将揭示产生具有不同骨骼阵列的化合物的折叠过程。这些复杂的小分子将通过使用高吞吐量筛选的技术来通过细胞增强剂分析和破译疾病途径来扰动生物学功能。将进行表型筛选和蛋白质结合测定，以生成用于药物开发和癌症治疗的直接潜在客户。