Synthesis of the sialyl Lewis X epitope attached to glycolipids with different core structures and their selectin-binding characteristics in a dynamic test system

Sialyl Lewis X (sLe(X))/selectin-mediated leukocyte rolling along endotheli al cells has recently gained wide interest. In this paper the influence of the spacer length of laterally clustered neoglycolipids 1a-d on cell rollin g in a dynamic test system is investigated. The required di-O-hexadecyl gly cerols with none, and with three, six, or nine ethylene glycol units as spa cer groups (compounds 4a-d) could be readily obtained. The synthesis of 1-O -thexyldimethylsilyl-protected sLe(X) 24 was based on sialylation of 2,3,4- O-unprotected galactose derivative 11 with sialyl phosphite 8 as donor; thi s afforded the desired disaccharide 12, which was transformed into trichlor oacetimidate 14 as disaccharide donor. Reaction of 3-O-unprotected glucosam ine derivative 18 with fucosyl donor 20 afforded disaccharide 21, which was transformed into the 4-O-unprotected derivative 23. Reaction of 14 with 23 furnished the desired tetrasaccharide 24 in good yield. Transformation of 24 into the trichloroacetimidate 26 as donor, followed by the reaction with 4a-d as acceptor gave, after deprotection, the target molecules 1a-d. For comparison, 4d was also connected with a sialyl residue (-->31) and with an N-acetylglucosamine residue (-->34). Compounds 1c and 1d with a hexaethyle ne glycol and a nonaethylene glycol spacer, respectively, were much more ef ficient in mediating selectin-dependent cell rolling in the dynamic test sy stem than compounds 1a and 1b, which had no spacer (1a), or only a triethyl ene glycol spacer (1b).