Synthetic Studies on Selectin Ligands/Inhibitors: A Systematic Synthesis of Sulfatide and Its Higher Congeners Carrying 2-(Tetradecyl)Hexadecyl Group as a Ceramide Substitute

Abstract

Abstract 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 β-D-galactopyranoside (21) via the 6-O-t-butyldimethylsilyl derivative, while the 3′-sulfate of 2-(tetradecyl)hexadecyl β-D-lactoside (VI) was synthesized from 2-(trimethylsilyl)ethyl 3′-O-benzyl-β-D-lactoside (26). The structures of the sulfated glycolipids (I-VI) were characterized by ion-spray MS, MS/MS, and 1H NMR spectrometry. 1. Synthetic studies on sialoglycocongugates, Part 96. For Part 95, see Y. Isogai, H. Ishida, M. Kiso and A. Hasegawa, J. Carbohydr. Chem., 15, 1119 (1996). Notes 1. Synthetic studies on sialoglycocongugates, Part 96. For Part 95, see Y. Isogai, H. Ishida, M. Kiso and A. Hasegawa, J. Carbohydr. Chem., 15, 1119 (1996).