Synthesis and thermotropic phase behavior of four glycoglycerolipids

Abstract

Four glycoglycerolipids with different head groups have been synthesized and their physicochemical properties studied. The lengths of the head groups from a mono-saccharide to a trisaccharide, in addition to the anomeric stereochemistry for the smaller glycoglycerolipids, have been modified. The synthesis has been optimized to avoid glycerol epimerization and to allow up-scaling. The physicochemical properties of the glycoglycerolipids were studied and a strong de-mixing of the gel-phase, depending on the head-group, was observed.

Scheme 1

Synthesis of the gentiobiosyl donor 2 and its glycosylation with 1,2-O-cyclohexylidene glycerol.

Scheme 2

Synthesis of gentiobiosyl building block 7.

Scheme 3

Global deprotection to give the glycolipids 15 (β-diglycolipid) and 16 (β-triglycolipid).

Scheme 4

Synthesis of pseudotetrasaccharide 10.

Scheme 5

Synthesis of donor 12 [32] and its glycosylation with pseudotrisaccharide 8.

Figure 1

Glycolipids 17 (α-monoglycolipid) and 18 (β-monoglycolipid).

Figure 2

DSC thermograms for (1) DMPS/DMPC, (2) DMPS/DMPC/β-monoglycolipid 18, (3) DMPS/DMPC/α-monoglycolipid 17, (4) DMPS/DMPC/β-diglycolipid 15, (5) DMPS/DMPC/β-triglycolipid 16. Vesicles at the compositions given in Table 1.

Figure 3

Confocal scanning fluorescence microscopy images for giant unilamellar vesicles containing β-diglycolipid 15 at 22 °C (A) and 37 °C (B). Vesicles composed of DMPC/DMPS/5 labeled with 0.1% DiI C18 (green) and 0.1% DiIC18 (red) were prepared as described in the supporting information. Color merged images were shown.