A method to use matrix-assisted laser desorption/ionization mass spect
rometry (MALDI-MS) for real-time monitoring of organic reactions on po
lymeric supports used in solid-phase synthesis is described. The strat
egy utilizes a synthetic construct that allows for the rapid and conve
nient direct MALDI analysis of the attached substrates as well as thei
r subsequent chemical cleavage as desired. We have used this strategy
to monitor nucleophilic substitutions, palladium-catalyzed coupling re
actions, and solid phase peptide synthesis reactions using both Boc- a
nd Fmoc-based chemistries. (C) 1997 Elsevier Science Ltd.