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 F-19 NMR spectroscopy. A fluorine-labeled dipeptide was synthesized on each resin, and the resolution of the F-19 resonances in CDCl3, DMSO-d(6), benzene-d(6) and CD3OD 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 F-19 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 F-19 NMR spectroscopy allowed each glycopeptide to be formed in similar to80% 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.