1- O, N-ditritylglycerophosphoethanolamine, a novel intermediate for the facile preparation of mixed-acid phosphatidylethanolamines

Abstract

A new method is described for the semisynthetic preparation of mixed-acid phosphatidylethanolamine (PE) having the natural steric configuration. Any phospholipid mixture from natural sources, e.g. soya phospholipids, can be used as the starting material. In the first step, PE is reacted with tritylbromide, and the resulting N-trityl-phosphatidylethanolamine is converted to N-trityl-glycerophosphoethanolamine ( N-trityl-GPE) by alkaline hydrolysis. Reaction with tritylchloride yields 1- O, N-ditrityl-GPE, which is acylated in the 2-position with, e.g. acylimidazolides. The 1- O-protecting trityl group is then selectively removed in the presence of borontrifluoride-methanol, and the second acyl moiety is introduced by acylation with fatty acid anhydrides. After N-detritylation with trifluoroacetic acid, the final product is obtained in high yield and with less than 10% of the positional isomer. The main advantages of the new method are that it requires only a few reaction steps, that some of the intermediates need not be isolated, and that no enzymatic reaction is involved. Thus, the procedure described here can be applied to the synthesis of mixed-acid PEs on a technical scale.