Solid-phase synthesis of modified oligopeptides via Passerini multicomponent reaction

A Passerini multicomponent reaction of N-protected-alpha-aminoaldehydes, carboxylic acids and solid-supported isocyanides has been successfully performed on Lantern(TM). The initially formed N-protected-beta-amino-alpha-acyloxyamides gave, by piperidine-promoted deprotection and concomitant acyl migration, beta-acylamino-alpha-hydroxyamides which, by OH-oxidation and cleavage off the solid support, provided beta-acylamino-alpha-oxoamides. Formation and disappearance of the isocyano group has been followed using photoacoustic IR spectroscopy, a fast, reliable and non-disruptive technique that has been successfully applied for the first time to macroscopic solid supports. (C) 2003 Elsevier Science Ltd. All rights reserved.