A high-yielding procedure for the semisynthesis of mixed-chain phosphatidylethanolamines is described. The key finding is that the reacylation of an N-tBOC-lysophosphatidylethanolamine methyl esterwith a carboxylic acid can be achieved in high yield with DCC and DMAP. Deprotection of the phosphate and amino functionalities with sodium iodide and trifluoroacetic acid, respectively, provides the title compounds. The versatility of this procedure is illustrated with the synthesis of several mixed-chain phosphatidylethanolamines.
Current investigations of the structure and function of biological membranes require efficient methods for the preparation of phospholipids. In particular, there is a growing need for mixed acid phospholipids with defined fatty acid composition,t for example, as: (1) components of artificial membranes for physicochemical studies,* (2) fluorescent,3 radiolabelled3a~4 and spin-labelled probes5 for the study of membrane motion, and (3) photoactivatable probes for investigations of protein-lipid interacttons.4a~c~ds A c ommonly employed synthetic method for synthesis involves specific deacylation of phospholipids at the sn-2 position with the use of phospholipase A2 and reacylation of the resulting 2lysophospholipids with the desired acid. However, there are problems associated with the second step that limit the utility of the method. In this paper we report an efficient variant of the reacylation procedure that utilizes protected phosphotriesters in the coupling reaction.
A summary of results obtained from current methods for the acylation of lysophospholipids is provided in Table .
Recent advances in coupling procedures have solved the problems of acyl migration and racemization (via the migration pathway) that accompanied the earlier methods. However, the methods generally employ an excess of the carboxylic acid