A facile route to semi-synthesis of acetyl glycerylether phosphoethanolamine and its choline analogue.

Abstract

A facile route to the semi-synthesis of acetyl glycerylether phosphoethanolamine and, subsequently, its choline analogue (platelet-activating factor) has been developed. In essence, this technique takes advantage of the fact that the phosphatidylethanolamine fraction of bovine erythrocytes contains 75–80% of a 1-O-alkyl-2 fatty acyl derivative. Isolation of the latter by silicic acid chromatography followed by base-catalyzed methanolysis allowed good recovery (60-70%) of the 1-O-alkyl-(lyso)-sn-glyceryl-3-phosphoethanolamine, which contained a mixture of long chain alkyl ethers. This compound was treated with acetic anhydride in the presence of trace amounts of perchloric acid for 45 sec to give, in excellent yield, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphoethanolamine (AGEPE). This procedure gave a 70% yield of purified AGEPE, based on the starting component, 1-O-alkyl-(lyso)-sn-glyceryl-3-phosphoethanolamine. Separation of AGEPE into fractions individually enriched in the 16:0, 18:0, and 18:1 alkylether substituents was accomplished by silica gel G combined with silver nitrate-impregnated silica gel H thin-layer chromatography. The AGEPE or its individual molecular species can be converted in high yields to the corresponding 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (AGEPC) analogues by reaction with methyl iodide in the presence of a crown ether. Characterization of the derivatives was achieved through thin-layer chromatography, infrared spectroscopy, gas-liquid chromatography, and combined gas-liquid chromatography-mass spectrometry. The ability of these analogues to induce irreversible aggregation and secretion of serotonin from washed rabbit platelets was evaluated.