Synthetic studies on selectin ligands/inhibitors: A systematic synthesis of sulfatide and its higher congeners carrying 2-(tetradecyl)hexadecyl group as a ceramide substitute

A systematic synthesis of sulfatide (I) and novel sulfatide analogs (II-VI) carrying 2-(tetradecyl)hexadecyl group as a ceramide substitute is described. The 3-O-, 4-O- and 3,4-di-O-levulinoyl derivatives of galactopyranosyl trichloroacetimidates (1, 12, and 13) were coupled with (2S,3R,4E)-3-O-acetyl-2-octadecanamido-4-octadecene-1,3-diol or 2-(tetradecyl)hexadecan-1-ol. The resulting glycolipids (2, 4, 14, and 15) were each transformed, by selective removal of the levulinoyl group(s), and successive sulfation and de-O-acylation, into the 3-sulfates (I, II), 4-sulfate (III), and 3,4-disulfate (IV). The 6-sulfate (V) was prepared from 2-(tetradecyl)hexadecyl beta-D-galactopyranoside (21) via the 6-O-t-butyldimethylsilyl derivative, while the 3'-sulfate of 2-(tetradecyl)hexadecyl beta-D-lactoside (VI) was synthesized from 2-(trimethylsilyl)ethyl 3'-O-benzyl-beta-D-lactoside (26). The structures of the sulfated glycolipids (I-VI) were characterized by ion-spray MS, MS/MS, and H-1 NMR spectrometry.