New method for organic synthesis based on affinity separation

提出了一种基于亲和分离（SAS）合成的高通量合成方法，该方法在溶液中进行反应，通过固体载体与具有主客体结构的产物之间的主客体相互作用，可以快速分离出所需产物。冠醚（32-冠-10）和铵离子之间的相互作用以前被发现是有用的。合成以冠醚标记的起始材料开始。每个反应循环后，将反应混合物应用于胺甲基化聚苯乙烯柱（三氟乙酸形式）。含有冠醚的化合物被选择性地吸附在柱上，而其他不含冠醚的杂质，如多余的试剂和副产物被洗掉。随后用CH_2CL_2-MeOH（1:1）解吸得到所需的高收率化合物。然后我们发现Triton X-100（聚乙二醇基洗涤剂）可以用作代替32-crown-10的标签。巴比妥酸衍生物与其人工受体间苯二甲酸双（2,6-二氨基吡啶）酰胺的相互作用也被发现是有效的。两种方法均应用于多肽、杂环和低聚糖的合成。用后一种方法合成了一种新的高效的脂质A，这是一种细菌的免疫刺激糖缀合物。用该方法构建了小脂质A文库。这些新策略有望在多并行合成和组合库制备方面发挥重要作用。

A new method named synthesis based on affinity separation (SAS) was developed for high throughput synthesis : the reaction is carried out in solution and the desired products can be isolated rapidly by the host-guest interaction between the solid-support and the desired products which possess the host and guest structures, respectively.The interaction between crown ether (32-crown-10) and ammonium ion was previously found to be useful for this purpose. The synthesis started with a starting material tagged with the crown ether. After each reaction cycle, the reaction mixture was applied to the aminomethylated polystyrene column (trifluoroacetic acid form). The compound possessing the crown ether was selectively adsorbed on the column, whereas other impurities without the crown ether such as excess reagents and byproducts were washed off. Subsequent desorption with CH_2CL_2-MeOH (1 : 1) afforded the desired compound in high yield. We then found Triton X-100 (polyethylene glycol based detergent) can be used as a tag in place of 32-crown-10.The interaction between a barbituric acid derivative and its artificial receptor [= bis(2,6-diaminopyridine)amide of isophthalic acid] was also found to be effective. Both methods were applied to the synthesis of peptides, heterocycles, and oligosaccharides. New efficient synthesis of lipid A, an immunostimulating glycoconjugate of bacteria, was achieved by using the latter method. The small lipid A library was also constructed by the method. These new strategies are expected to be useful for, particularly, multiple parallel synthesis and combinatorial library preparation.