Regioselective reactions for programmable resveratrol oligomer synthesis.
Regioselective reactions for programmable resveratrol oligomer synthesis.
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DOI：
10.1038/nature10197
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发表时间：
2011-06-22
期刊：
影响因子：
64.8
通讯作者：
Chiriac, Maria I.
中科院分区：
文献类型：
--
作者：
Snyder, Scott A.;Gollner, Andreas;Chiriac, Maria I.
白藜芦醇是一种由世界各地的植物产生的独特的多酚，由于其广谱活性，白藜芦醇被认为可能是造成所谓“法国悖论”的原因，尽管白藜芦醇衍生的数百种低聚物质具有同样高的生化潜力，但它们在很大程度上被忽视了。主要原因是难以从自然来源中大量分离出这些物质，再加上无法在实验室中合理制备这些物质。在这里，我们展示了一个可编程的、可控的、潜在的可扩展的白藜芦醇家族的合成是可能通过一个独特的三段式设计。这些努力需要新颖的策略，加上策略和试剂引导的功能化，以区分两个不同的核心，这些核心拥有多个具有相同和/或相似反应性的位点，最终产生五种高阶天然产物。我们预计这项工作1)证明了复杂材料的具有挑战性的、位置选择性的功能化是可能的，在生物合成研究表明相反的情况下，2)提供了材料和工具，最终释放了该家族的全部生化潜力，特别是从活性和药物性能优化的角度来看，3)提供了一个潜在的知识框架，可以控制地访问其他寡聚家族。
Although much attention has been devoted to resveratrol, a unique polyphenol produced by plants throughout the world and credited as potentially being responsible for the so-called “French paradox” given its broad spectrum activity, the hundreds of oligomeric materials derived from it have been largely ignored despite their similarly high biochemical potential. Challenges in achieving their isolation in quantity from natural sources, coupled with an inability to rationally prepare them in the laboratory, are the main culprits. Here we show that a programmable, controlled, and potentially scaleable synthesis of the resveratrol family is possible through a unique three-stage design. These efforts required novel tactics coupled with strategy- and reagent-guided functionalizations to differentiate two distinct cores possessing multiple sites with the same and/or similar reactivity, ultimately leading to five higher-order natural products. We anticipate that this work 1) demonstrates that challenging, positionally-selective functionalizations of complex materials are possible where biosynthetic studies have indicated otherwise, 2) provides materials and tools to finally unlock the full biochemical potential of the family, particularly from the standpoint of activity and drug-property optimization, and 3) affords an intellectual framework to potentially access other oligomeric families controllably.
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DOI：
10.1126/science.1188403
发表时间：
2010-06-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gustafson JL;Lim D;Miller SJ
通讯作者：
Miller SJ
影响因子：
3.6
作者：
BOGER, DL;BROTHERTON, CE
通讯作者：
BROTHERTON, CE
影响因子：
2.1
作者：
Kurosawa, W;Kobayashi, H;Fukuyama, T
通讯作者：
Fukuyama, T
影响因子：
2
作者：
Li, Wenling;Li, Hongfu;Wang, Nong
通讯作者：
Wang, Nong
影响因子：
64.8
作者：
Chen, Ke;Baran, Phil S.
通讯作者：
Baran, Phil S.