Synthesis of 1-sn-lysophosphatidylcholine and mixed acid 1-sn-phosphatidylcholine

An investigation of the biochemical effects of L-lysophosphatidylcholine (1-acyl-sn-glycerol-3-phosphorylcholine) requires as a control for its detergent action the metabolically inert, unnatural enantiomer, D-lysophosphatidylcholine (3-acyl-sn-glycerol-1-phosphorylcholine). The latter can be easily prepared in milligram quantities from the commercially available DL-phosphatidylcholine. For this purpose rac-1,2-dipalmitoyl-sn-glycerol-3-phosphorylcholine is solubilized with the aid of one-half its weight of taurocholate and hydrolyzed with phospholipase A2 to completion and the intact residual 2,3-dipalmitoyl-sn-glycerol-1-phosphorylcholine recovered by chromatography. The pure D-phosphatidylcholine is then subjected to methanolysis in the presence of octylamine and the product isomerized with glacial acetic acid. The 3-palmitoyl-sn-glycerol-1-phosphorylcholine thus obtained is chromatographically pure, possesses correct optical rotation and NMR spectrum, and is resistant to hydrolysis by phospholipase A2 following reacylation to the diacylphosphatide. Acylation of the 1-sn-lysophosphatide provides a convenient method for preparation of mixed acid 1-sn-phosphatidylcholines which are not otherwise available.