PHOSPHOLIPID-SYNTHESIS USING POLYMER-SUPPORTED PROTECTIVE GROUPS

Polystyrene-supported glycerophosphorylethanolamine (GPE), in which the amino group is protected by a triphenylmethyl group, was prepared by methanolysis of polystyrene-supported natural phosphatidylethanolamine. Immobilized GPE was acylated with fatty acid anhydrides in the presence of 4-(dimethylamino)pyridine or with acylimidazoles in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene in chloroform. Immunobilized GPE containing acyl residues was treated with trifluoroacetic acid in dichloromethane to afford free monoacylated and diacylated phosphatidylethanolamines (PEs). The monoacylated product (lyso PE) with a sec-hydroxyl group was preferentially obtained in 45-70% yield, when the ratio of the acylating agent to the hydroxyl group of GPE was 1.0. The diacylated product was obtained in 70-75% yield by the acylation at a ratio of 4. Such a solid-phase phospholipid synthesis resulted in easy separation and purification of lipid intermediates, compared with the lipid synthesis under homogeneous conditions.