Synthesis of Small Molecules with High Scaffold Diversity: Exploitation of Metathesis Cascades in Combination with Inter- and Intramolecular Diels-Alder Reactions
Synthesis of Small Molecules with High Scaffold Diversity: Exploitation of Metathesis Cascades in Combination with Inter- and Intramolecular Diels-Alder Reactions
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DOI：
10.1002/chem.201000707
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Nelson, Adam
中科院分区：
文献类型：
--
作者：
O'Leary-Steele, Catherine;Pedersen, Palle J.;Nelson, Adam
我们对化学空间区域的生物相关性的认识在很大程度上是由小分子的合成可及性形成的。然而，从历史上看，化学家对化学空间的探索是以一种异常不平衡和不系统的方式进行的。我们之前已经证明，可以利用复分解级联化学来产生具有高支架多样性的小分子集合。在这里，我们描述了分子间和分子内Diels-Alder反应，当与复分解级联结合使用时，可以扩展可访问的分子支架的范围。由两种或三种结构单元的组合制备一系列复分解底物。利用复分解级联来“重编程”分子支架。在许多情况下，复分解产物是1，3-二烯，其是分子间或分子内Diels-Alder反应的潜在底物。产物的合成和功能化通常通过氟标记来促进，例如通过使用我们开发的“安全捕获”连接体。已经证明，在某些情况下，Die Is桤木反应可以扩展可以通过使用复分解级联反应制备的分子支架的范围。
Our knowledge of the biological relevance of regions of chemical space is shaped, in large part, by the synthetic accessibility of small molecules. Historically, however, chemists have explored chemical space in an exceptionally uneven and unsystematic way. We have previously demonstrated that metathesis cascade chemistry may be harnessed to yield small molecule collections with high scaffold diversity. Here, we describe the extent to which inter- and intramolecular Diels-Alder reactions, when used in conjunction with metathesis cascades, can extend the range of molecular scaffolds that are accessible. A range of metathesis substrates was prepared from combinations of two or three building blocks. Metathesis cascades were exploited to "reprogram" the molecular scaffolds. In many cases, the metathesis products were 1,3-dienes, which were potential substrates for either inter- or intramolecular Diels-Alder reactions. The synthesis and functionalisation of the products was often facilitated by fluorous tagging, for example by using a "safety-catch" linker that we have developed. It was demonstrated that, in certain cases, Die Is Alder reactions could extend the range of molecular scaffolds that may be prepared by using metathesis cascade reactions.