Phospholipid synthesis: Oxazaphospholanes and dioxaphospholanes as intermediates

Abstract

The synthesis of phospholipids described herein allows an almost quantitative conversion of 1,2-diacylglycerols to phospholipids via cyclic intermediates such as oxazaphospholanes or dioxaphospholanes, which are the only products observed when ethanolamine or ethylene glycol is allowed to react with phosphatidic acid dichlorides. The acidic hydrolysis of the cyclic intermediates occurs rapidly without the formation of by-products and results in phospholipids differing in the structure of the polar part depending on which vicinal aminoalcohols or diols are used. For instance, phosphatidylethanolamines, -(N-methyl)ethanolamines, and -serine benzyl esters are directly formed from the corresponding oxazaphospholanes. Phosphatidyl(N,N-dimethyl)ethanolamines and -cholines are prepared by amination of the bromoethyl esters of phosphatidic acids, which can be obtained by treatment of dioxaphospholanes with sodium bromide. A similar sequence of reactions starting from 1-acyl-2-benzylglycerols or monoacylpropane-1,3-diols will result in the respective monoacyl analogues such as lysophospholipids or the so-called desoxylysophospholipids. The mild reaction conditions, good yields (>90% based on diacylglycerol), and high purity of the products make this route an attractive procedure for phospholipid synthesis; in addition, it avoids the need for chromatography and thus can be utilized on a large scale.