Twelve-membered macrolactones: privileged scaffolds for the development of new therapeutics
Twelve-membered macrolactones: privileged scaffolds for the development of new therapeutics
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DOI：
10.1111/cbdd.12783
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发表时间：
2017-02-01
影响因子：
3
通讯作者：
Wuest, William M.
中科院分区：
文献类型：
--
作者：
Brzozowski, Richard S.;Wuest, William M.
通常作为各种植物和微生物的次生代谢物产生的天然产物代表了化合物的多样化化学空间。天然产物的多样性使它们成为化学家和生物学家研究的有吸引力的目标。事实上，12 元大环内酯的研究已经导致了先导药物化合物和新生物靶点的发现，这推动了类似物库的全合成路线的开发。本综述探讨了几种 12 元大环内酯的发现、生物学表征和合成，并利用例子强调了它们在药物发现领域的重要性。我们希望这篇综述能够激发人们对这类天然产物的进一步兴趣，我们认为这些分子值得在药物化学界归类为“特权支架”，以进一步研究和开发具有前景生物活性的新型化合物。
Natural products commonly produced as secondary metabolites of various plants and micro-organisms represent a diverse chemical space of compounds. The diversity of natural products makes them an attractive target for interrogation by both chemists and biologists alike. Indeed, the study of 12-membered macrolactones has already led to the discovery of lead drug compounds and new biological targets, which has motivated the development of diverted total synthetic routes to libraries of analogs. This review explores the discovery, biological characterization, and synthesis of several 12-membered macrolactones, exploiting examples that underscore their importance in the drug discovery field. It is our hope that this review will motivate further interest in this class of natural products, a group of molecules that we think merit the classification of 'privileged scaffolds' within the medicinal chemistry community, to further investigate and develop novel compounds with promising bioactivity.