Synthesis and NMR analysis of model compounds related to fucosylated chondroitin sulfates: GalNAc and Fuc(1 → 6)GalNAc derivatives

Abstract

Unsubstituted and 6-O-α-L-fucosylated propyl 2-acetamido-2-deoxy-β-D-galactopyranosides and their selectively O-sulfated (both in GalNAc and Fuc units) derivatives were synthesized as model compounds representing the fragments of fucosylated chondroitin sulfates (FCS) from sea cucumbers. Per-O-acetylated 2-deoxy-2-N-phthalimido-D-glucopyranose was used as a key precursor for the preparation of all 2-acetamido-2-deoxy-D-galactopyranoside containing products. Attempts at 6-O-glycosylation of propyl 3-O-benzoyl-2-deoxy-2-N-phthalimido-D-galactoside by 2-O-benzyl-3,4-di-O-chloracetyl-L-fucosyl trichloracetimidate in the presence of TMSOTf gave a 1:1 mixture of the corresponding α- and β-isomeric disaccharides, while the use of structurally related fucosyl bromide donor with promotion by Bu₄NBr led to the formation of desired α-isomeric disaccharide exclusively. Selective removal of orthogonal O-protections permitted subsequent O-sulfation both at the GalNAc and Fuc units. Further removal of blocking groups yielded the target products which were systematically studied by ¹H and ¹³C NMR spectroscopy in order to determine the spectral effects of O-sulfation and α-L-fucosylation needed for the development of computer assisted structural analysis of natural FCS.

Keywords: Fucosylated chondroitin sulfate; Glycosylation; NMR; Oligosaccharide; Spectral glycosylation effect; Spectral sulfation effect; Synthesis.