Synthesis of various sulfoforms of the trisaccharide β-D-GlcpA-(1→3)-β-D-Galp-(1→3)-β-D-Galp-(1→OMP) as probes for the study of the biosynthesis and sorting of proteoglycans

A straightforward preparation of various sulfoforms of the trisaccharide 4-methoxyphenyl O-(sodium beta-D-glucopyranosyluronate)-(1-->3)-(P-D-galactopyranosyl)-(1-3)-beta-D-galactopyranoside (1), namely its 6a- and 4a-monosulfate, 6b- and 4b-monosulfate and 6a,6b-disulfate derivatives, is reported for the first time. These compounds, which are partial structures of the linkage region of proteoglycans, will serve as probes for the study of the biosynthesis and sorting of these macromolecules. A key trisaccharide derivative, in which the two similar D-Gal units were differentiated at C-4,6 with 4,6-benzylidene and 4,6-di-tert-butylsilyiene acetals, respectively, was used as a common intermediate. Both acetal groups showed excellent orthogonality, and allowed the preparation of all target compounds in high yield. Noteworthy is the possibility to prepare the 6a- and 6b-monosulfated and the 6a,6b-disulfated species through a one-pot regioselective procedure starting from a tetrol precursor.