Gel-phase 19F NMR spectral quality for resins commonly used in solid-phase organic synthesis; a study of peptide solid-phase glycosylations

The spectroscopic properties for seven different commercial resins used in solid-phase synthesis were investigated with (19)F NMR spectroscopy. A fluorine-labeled dipeptide was synthesized on each resin, and the resolution of the (19)F resonances in CDCl(3), DMSO-d(6), benzene-d(6) and CD(3)OD were measured with a conventional NMR spectrometer, i.e. without using magic angle spinning. In general, resins containing poly(ethylene glycol) chains (ArgoGel, TentaGel and PEGA) were found to be favorable for the (19)F NMR spectral quality. Three serine containing tri-, penta-, and heptapeptides were then prepared on an ArgoGel resin functionalized with a fluorine-labeled linker. The resin bound peptides were glycosylated utilizing a thiogalactoside glycosyl donor carrying fluorine-labeled protective groups. Monitoring of the glycosylations with gel-phase (19)F NMR spectroscopy allowed each glycopeptide to be formed in similar 80% yield, using a minimal amount of glycosyl donor (3 x 2 equivalents). In addition, it was found that the glycosylation yields were independent of peptide length.