SYNTHESES OF POLYMERIZABLE MONOACYLGLYCEROLS AND 1,2-DIACYL-SN-GLYCEROLS

The first chemical syntheses of polymerizable monoacylglycerol and 1,2 -diacyl-sn-glycerol are reported. The monodienoylglycerol is obtained in 80% yield from 1,2-O-isopropylidene-sn-glycerol and dienoyl fatty a cid. The dienoic acid is accessible in 60% yield from the base-catalyz ed hydrolysis of dienoyl ester, which is synthesized from the Wittig-H orner reaction of aldehyde and trimethyl 4-phosphonocrotonate. The acy lation is carried out in the presence of 4-(dimethylamino)pyridine and dicyclohexylcarbodiimide. The use of excess protected glycerol relati ve to fatty acid affords the acylated product in high yield. The final step is the deprotection of isopropylidene group using dilute HCl sol ution. The 1,2-diacyl-sn-glycerol is synthesized by acylation of 3-(4- methoxybenzyl)-sn-glycerol with dienoyl fatty acid in the presence of 4-(dimethylamino)pyridine and dicyclohexylcarbodiimide. The removal of the 4-methoxybenzyl group by dimethylboron bromide catalyzed hydrolys is is especially useful in the synthesis of polymerizable lipids becau se the deprotection proceeds without any apparent effect on the dienoy l polymerizable group and without detectable isomerization of 1,2-diac ylglycerol to 1,3-diacylglycerol. The overall yield for the synthesis of the polymerizable 1,2-diacyl-sn-glycerol from the dienoyl fatty aci d is ca. 50%.