Synthesis towards an aromatic alfa-dixyloside

Abstract: A proteoglycan is a protein with at least one glycosidic chain or glycosaminoglycan (GAG) covalently bound to it. Since a common linker between the core protein and the GAG chain has a xylose present, the biosynthesis of GAGs can be primed using xylosides containing hydrophobic aglycons providing that these xylosides are capable of penetrating the cell membrane. 2-naphthyl β-D-xylopyranoside primes synthesis of chondroitin sulfate/dermatan sulfate and heparan sulfate/heparin as showed by Mani et. al. and in addition 2-(6-hydroxynaphthyl) β-D-xylopyranoside also shows selective antiproliferative effect between normal cells and cancer cells. Also Bakker et. al recently showed that oligosaccharides containing dixylopyranosides linked α1-3 show biological activity in mammalian cells. These findings gave the idea that α–linked aromatic dixylopyranosides might prime GAG synthesis, if their polarity allows them to penetrate the cell membrane, and show antiproliferative effect. In this report, a synthetic pathway towards an aromatic dixyloside 2-naphthyl α-D-xylopyranoside-(1-4)-1-O-α-D-xylopyranoside was attempted using α-selective O-glycosylation with thioxylosides on aromatic xylosides with suitable protective groups. An aromatic α-dixyloside was indeed produced in somewhat low yields, but the last deprotection step in the synthetic pathway tended to break the glycosidic bond between the xylosides.