Epoxide-opening cascades promoted by water
Epoxide-opening cascades promoted by water
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DOI：
10.1126/science.1146421
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发表时间：
2007-08-31
期刊：
影响因子：
56.9
通讯作者：
Jamison, Timothy F.
中科院分区：
文献类型：
--
作者：
Vilotijevic, Ivan;Jamison, Timothy F.
有机化学中的选择性规则在很大程度上是从非水环境中推断出来的。相比之下，酶在水中工作，介质变化的化学效应仍然只有部分了解。“阶梯”聚醚海洋天然产物的结构表征提出了一个持续了20年的难题：尽管相邻四氢吡喃（THP）环的立体化学似乎来自环氧化物开放反应的生物合成级联，但有机溶剂中的经验始终认为这样的途径在动力学上是不利的。我们报告说，中性水作为一个最佳的促进剂所需的开环选择性，一旦一个单一的模板THP附加到链的环氧化物。这种策略提供了一种高产量的路线，以天然存在的阶梯核心，并强调了可能的重要性，水介质的影响，在支持某些值得注意的酶的选择性。
Selectivity rules in organic chemistry have been inferred largely from nonaqueous environments. In contrast, enzymes operate in water, and the chemical effect of the medium change remains only partially understood. Structural characterization of the " ladder" polyether marine natural products raised a puzzle that persisted for 20 years: Although the stereochemistry of adjacent tetrahydropyran ( THP) cycles would seem to arise from a biosynthetic cascade of epoxide-opening reactions, experience in organic solvents argued consistently that such a pathway would be kinetically disfavored. We report that neutral water acts as an optimal promoter for the requisite ring-opening selectivity, once a single templating THP is appended to a chain of epoxides. This strategy offers a high- yielding route to the naturally occurring ladder core and highlights the likely importance of aqueous-medium effects in underpinning certain noteworthy enzymatic selectivities.