Solid-phase/solution-phase combinatorial synthesis of neuroimmunophilin ligands

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.