New methodology for high throughput solution-phase synthesis: affinity purification by using crown ether and ammonium ion interaction

A new method for affinity purification of synthetic compounds by using crow n ether-ammonium ion interaction and its application to the synthesis of se veral peptides and heterocycles are described. The desired compounds posses sing the crown ether (32-crown-10) moiety were readily isolated from the re action mixture by the following procedure. After each reaction cycle, the r eaction mixture was applied to the aminomethylated polystyrene column (trif luoroacetic acid form). The compound possessing the crown ether was selecti vely adsorbed on the column, whereas other impurities without the crown eth er such as excess reagents and byproducts were washed off. Subsequent desor ption by Et3N or CH2Cl2:MeOH (1:1) afforded the desired compound with high purity. This new strategy is expected to be useful, for, in particular, mul tiple parallel synthesis and combinatorial library preparation. (C) 1999 El sevier Science Ltd. All rights reserved.