| Abstract
| - Glycosyl diacylglycerols are excellent lipids for the formation of both bi- and monolayer lamellarsystems but they are generally not commercially available, and the synthesis of optically pure glycosyldiacylglycerols inevitably involves protection and deprotection of glycerol linkers. A novel glycolipid designedto be an easily accessible structural surrogate of monoglucosyl diacylglycerol (MGDG) has been synthesized.In this molecule, glycerol is replaced with (S)-1,2,4-trihydroxybutane. Instead of the fatty acyl moieties foundin MGDG, a 2,2-dialkyl-1,3-dioxolane function provides the hydrophobic moiety of the molecule. This differentfunctionality affords chemically and physically tunable new properties in a glycolipid. These include basestability, increased mobility of the headgroup, possibilities of new packing arrangements, and the potential foruse in encapsulation strategies using liposomes where a decrease in pH is used as the environmental cue forrelease. The acetal linkage also makes the molecule unsusceptible to degradation by phospholipase A andother esterase activities found in biological systems thus further extending their utility. The choice of thebutane triol linker removes the common problem of racemization of protected glycerol by acetal and estermigration. It also affords synthetic simplicity since only one dioxolane acetal is formed on reaction of butane-1,2,4-triol with ketones, whereas in the case of glycerol, one hydroxyl group has to be selectively protected toavoid the formation of both enantiomers. 2-D NMR homonuclear and heteronuclear correlation spectroscopytogether with nuclear Overhauser effect experiments and molecular mechanics calculation were used to obtaininformation on the headgroup orientation and on the configuration of the trialkoxybutane backbone. Thesesupported a structure in which the alkyl chains were extended in a parallel fashion and the headgroup, althoughfree to rotate along C2−C3 and C3−C4 of the trialkoxybutane substructure, extended away in the other directionin a manner similar to that observed in the case of MGDG. X-ray powder diffraction and optical microscopydata both supported a lamellar phase behavior of this amphiphilic molecule in water. 1H NMR experimentsmonitoring the rate of acetal cleavage of this amphiphile revealed its tunable acid susceptibility. The uniquestructural feature, phase behavior, and controllable acid susceptibility of this glycolipid is potentially useful inmany applications.
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