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

Abstract

The spectroscopic properties for seven different commercial resins used in solid-phase synthesis were investigated with ¹⁹F NMR spectroscopy. A fluorine-labeled dipeptide was synthesized on each resin, and the resolution of the ¹⁹F resonances in CDCl₃, DMSO-d₆, benzene-d₆ 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 ¹⁹F 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 ¹⁹F NMR spectroscopy allowed each glycopeptide to be formed in ∼80% yield, using a minimal amount of glycosyl donor (3 × 2 equivalents). In addition, it was found that the glycosylation yields were independent of peptide length.