Attempts to prepare tethered bilayer lipid membranes using synthetic thioglycolipid anchors: synthesis of 6″-thiotrisaccharide glycolipid analogues and applications

• Synthesis of 6″-deoxy-6″-thio trisaccharide propargyl glycosides.
• Click chemistry with 1-azidododecane and 1-azidooctadecane.
• Zemplén deprotection gave disulfides of 6″-thio glycolipid trisaccharides.
• Mono- and bilayers on Au(1 1 1) surface were assessed by differential capacitance.
• A monosaccharide glycolipid tethered an artificial bilayer lipid membrane on Au(1 1 1).

The synthesis of the three 6″-deoxy-6″-thio glycolipid analogues β-d-Gal-(1→6)-β-d-Gal-(1→4)-β-d-Glu-(1→OCH2)-[1,2,3]-triazole-1-dodecane, β-d-Gal-(1→4)-β-d-Glu-(1→4)-β-d-Glu-(1→OCH2)-[1,2,3]-triazole-1-dodecane and β-d-Gal-(1→4)-β-d-Glu-(1→4)-β-d-Glu-(1→OCH2)-[1,2,3]-triazole-1-octadecane is presented. Glycosylation at position O-4′ of a propargyl cellobioside glycosyl acceptor and position O-6′ of a propargyl lactoside glycosyl acceptor with a 6-deoxy-6-thio galactosyl donor gave rise to two unique trisaccharides that in turn underwent copper-catalyzed azide–alkyne cycloadditions with either 1-azidododecane or 1-azidooctadecane. The potential for each of these analogues to function as tethers of lipid bilayers to Au(1 1 1) surface was assessed by differential capacitance experiments. A monolayer of the previously described monosaccharide 1-octadecane-4-(6-thio-β-d-galacto-pyranosyloxymethyl)-[1,2,3]-triazole either self-assembled or prepared by Langmuir–Blodgett (LB) transfer was found to support an outer leaflet monolayer (DMPC/cholesterol, 70:30) deposited by Langmuir–Schaefer (LS) touch. The bilayers obtained with this monosaccharide analogue had minimum differential capacitances of 1.0 and 0.9 μF/cm2 when the inner monolayer was prepared by self-assembly and LS touch, respectively. Attempts to produce bilayers using the trisaccharides synthesized here were unsuccessful; we are attributing these unsuccessful results mostly to the high water solubility of trisaccharides combined with the relatively short length of the hydrocarbon chains used in this study.

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