Luo Z, Zhang Q, Oderaotoshi Y, Curran D P
Department of Chemistry and Center for Combinatorial Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Science. 2001 Mar 2;291(5509):1766-9. doi: 10.1126/science.1057567.
The solution-phase synthesis of organic compounds as mixtures rather than in individual pure form offers efficiency advantages that are negated by the difficulty in separating and identifying the components of the final mixture. Here, a strategy for mixture synthesis that addresses these separation and identification problems is presented. A series of organic substrates was tagged with a series of fluorous tags of increasing fluorine content. The compounds were then mixed, and multistep reactions were conducted to make enantiomers or analogs of the natural product mappicine. The resulting tagged products were then demixed by fluorous chromatography (eluting in order of increasing fluorine content) to provide the individual pure components of the mixture, which were detagged to release the final products.
以混合物而非单一纯净形式进行有机化合物的溶液相合成具有效率优势，但最终混合物各成分的分离和鉴定困难抵消了这些优势。本文提出了一种解决这些分离和鉴定问题的混合物合成策略。一系列有机底物用一系列氟含量递增的氟标签进行标记。然后将这些化合物混合，并进行多步反应以制备天然产物马皮辛的对映体或类似物。接着通过氟色谱法（按氟含量递增顺序洗脱）将得到的带标签产物分离，以提供混合物的各个纯净成分，去除标签后得到最终产物。
