Infrared and Raman Spectra of a Single Resin Bead for Analysis of Solid-Phase Reactions and Use in Encoding Combinatorial Libraries

A range of lysine amides 2 to 7 tagged with different combinations of either Raman- and/or infrared (IR)-active groups (4-cyanobenzoyl chloride, 3,5-di-tert-butyl-4-hydroxybenzoic acid, or 4-pentynoic acid) have been synthesized on Sasrin resin. Randomly selected beads of unknown identity were then analyzed by Fourier transform infrared (FTIR) and Raman microspectrometry. Using a combination of these two spectroscopic techniques, the six amide derivatives 2 to 7 and the unfunctionalized lysine template 1 were unambiguously identified from their Raman and FTIR spectra. The potential applications of FTIR and Raman microspectrometry for analysis of organic reactions on solid support and for encoding combinatorial libraries has been demonstrated.