Infrared Spectrum of a Single Resin Bead for Real-Time Monitoring of Solid-Phase Reactions

摘要

Two applications of combinatorial chemistry, lead-finding and chemical analoging, are likely to rely on solid-phase synthesis to facilitate the assembly of combinatorial libraries of compounds. Because of the inadequate pharmaceutical properties of peptides and nucleotides, intense effort has been on the generation of small, organic compound libraries. A major hindrance t6 this work has been the lack of analytical methods to establish the degree to which the expected chemistry has proceeded on polymer supports. Even more difficulties are encountered for monitoring solid-phase reactions during the course of a reaction (real-time monitoring). We report here a novel single-bead FTIR microspectroscopy method for real-time monitoring of organic synthesis on resin support. We describe (1) the determination of the extent of conversion from starting materials to products, (2) the ability of a single bead to be representative of a mass of beads, and (3) the monitoring of the time course of a reaction.