A novel solid-phase/solution-phase strategy for the synthesis of neuroimmun
ophilin ligands based on GPI 1046 was developed. The synthesis employs a so
lid-phase esterification strategy followed by a solution-phase pyruvic amid
e formation to produce multi-milligram quantities of discrete compounds for
assay. The protocol was applied to a production library of 880 discrete co
mpounds. A highlight of the strategy is an aqueous extractive purification
of the final compounds using a novel liquid/ice extraction system developed
for high throughput. (C) 2000 Published by Elsevier Science Ltd.