Department of Chemistry, 1101 Chevron Science Center, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, USA.
Nat Chem. 2012 Jan 10;4(2):124-9. doi: 10.1038/nchem.1233.
Fluorous mixture synthesis minimizes the effort to synthesize small-molecule libraries by labelling the molecules rather than the reaction vessels. Reactants are labelled with fluorinated tags and products can later be demixed based on the fluorine content. A limit in the number of available tags can be overcome by using binary encoding so that a total of four tags can label uniquely a library of 16 compounds. This strategy, however, means that separation based on fluorine content alone is not possible. Here, we solve this problem by selectively removing one tag after an initial demixing step; a second demixing provides each individual compound. The usefulness of this strategy is demonstrated by the synthesis of a library that contains all 16 diastereomers of the natural products macrosphelides A and E. Macrosphelide D was not in this library, and so its assigned structure was incorrect. We determined its constitution by using NMR spectroscopy and its configuration by synthesizing four candidate stereoisomers.
氟相混合物合成通过标记分子而不是反应容器，将小分子文库的合成工作量最小化。反应物用氟化标签标记，产物可以根据氟含量进行分离。通过使用二进制编码，可以克服可用标签数量的限制，从而总共四个标签可以唯一标记 16 个化合物的文库。然而，这种策略意味着仅基于氟含量进行分离是不可能的。在这里，我们通过在初始分离步骤后选择性地去除一个标签来解决这个问题；第二次分离提供每个单独的化合物。通过合成包含天然产物大球壳菌素 A 和 E 的所有 16 对对映异构体的文库，证明了该策略的有效性。该文库中不包含大球壳菌素 D，因此其分配结构不正确。我们通过使用 NMR 光谱确定了它的结构，并通过合成四个候选立体异构体确定了它的构型。
