A synthesis of phospholipids using a phosphite-triester approach and uniformly cleavable β-halogenated protecting groups

A new method for the synthesis of phospholipids is described. It is characterized by the use of a phosphite-amide-triester strategy, adopted from oligonucleotide chemistry, and by the use of protective groups which are cleavable by reductive fragmentation. Phosphorous acid-1,1,1-trichloro-2-methyl-2-propylester- (TCB) chloride-dimethylamide is used as the phosphorylating agent. Thus TCB is used for the protection of phosphodiesters. Nitrogenfunctions are protected by the 1,1,1-trichloro-2-methyl-2-propyl-oxycarbonyl group (TCBOC) and 2-bromoethanole is used for the protection of carboxyl groups. The versatility of this method is demonstrated by the syntheses of 1,2-dimiristoyl-sn-glycero-3-phosphatidyl-ethanolamine (DMPE) and 1,2-dimyristoyl-sn-glycero-3-phosphatidyl-serine (DMPS).