Synthesis based on affinity separation (SAS): Separation of products having barbituric acid tag from untagged compounds by using hydrogen bond interaction

A new method is described for affinity purification of synthetic compounds based on molecular recognition between bis(2,6-diaminopyridine)amide of isophthalic acid and a barbituric acid derivative. The desired compounds possessing the barbituric acid derivative as a tag were readily isolated from the reaction mixture by the following procedure. After each reaction cycle, the reaction mixture was applied to the polystyrene column possessing bis(2,6-diaminopyridine)amide of isophthalic acid as an artificial receptor. The compound possessing the barbituric acid tag was selectively adsorbed on the column, whereas other impurities without the tag such as excess reagents and byproducts were washed off. Subsequent desorption with CH₂Cl₂-MeOH (1:1) afforded the desired compound with high purity. This new strategy was applied to the synthesis of a heterocycle, peptides, and oligosaccharides.