通过支化反应途径实现多样性：多环支架的生成和抗迁移剂的鉴定。
Diversity through a branched reaction pathway: generation of multicyclic scaffolds and identification of antimigratory agents.
机构信息
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA.
出版信息
Chemistry. 2011 Jan 10;17(2):649-54. doi: 10.1002/chem.201002195. Epub 2010 Nov 9.
Abstract
A library of 91 heterocyclic compounds composed of 16 distinct scaffolds has been synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels-Alder reactions, and, in some cases, hydrolysis. This effort in diversity-oriented synthesis produced a collection of compounds that exhibited high levels of structural variation both in terms of stereochemistry and the range of scaffolds represented. A simple but powerful sequence of reactions thus led to a high-diversity library of relatively modest size with which to explore biologically relevant regions of chemical space. From this library, several molecules were identified that inhibit the migration and invasion of breast cancer cells and may serve as leads for the development of antimetastatic agents.
摘要
通过一系列膦催化的成环反应、Tebbe 反应、Diels-Alder 反应以及在某些情况下的水解反应，合成了一个由 16 种不同支架组成的 91 种杂环化合物库。这种多样性导向合成的努力产生了一系列化合物，这些化合物在立体化学和所代表的支架范围方面都表现出了高度的结构变化。因此，一个简单而强大的反应序列导致了一个相对较小的高多样性文库，可以用来探索具有生物学相关性的化学空间区域。从这个文库中，鉴定出了几种能够抑制乳腺癌细胞迁移和侵袭的分子，它们可能成为开发抗转移药物的先导化合物。
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