A simple chemical synthesis of the ether analog of lysophosphatidylcholine and platelet-activating factor

Abstract

A simple chemical procedure for synthesis of 1-O-alkyl-(rac or sn)-glycero-3-phosphocholine (alkyl analog of lysophosphatidylcholine, II) and platelet activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (III) has been described. The key step of the method is the decomposition of 1-O-hexadecyl-3-diazohydroxyacetone (A. K. Hajra, T. V. Saraswathi and A. K. Das, 1983. Chem. Phys. Lipids. 33: 179-193) with phosphocholine to synthesize 1-O-hexadecyl dihydroxyacetone-3-phosphocholine (I). Conditions for this phosphorolysis were studied with respect to the reaction medium, temperature, and optimum proportion of the reactants. Compound (I) was quantitatively reduced with NaBH4 to synthesize (II) which was acetylated to prepare compound (III). Phospholipase A2 hydrolysis of compound (III) followed by separation of the products afforded the unreacted sn-3-hexadecyl isomer (III) and sn-1-hexadecyl isomer (II) which was acetylated to PAF. The structures of the compounds were verified by NMR and FAB-MS spectra, and their biological activities were determined by measuring the release of serotonin from rabbit blood platelets in response to different doses of these compounds. The suitability of the method as a general technique for synthesis of different ether phosphoglycerides is discussed.