Stereospecific Synthesis of Ether Phospholipids. Preparation of 1-Alkyl-2-(acylamino)-2-deoxyglycerophosphorylcholines

Article abstract of DOI:10.1021/jo00156a011

A novel stereospecific synthesis of biologically active ether phospholipids is reported.The synthesis is based upon (1) utilizing L-serine to provide the chiral center, (2) developing the aliphatic ether function by coupling the methanesulfonate of the fatty acid alcohol with an oxazoline-protected deoxyglyceride, and (3) introducing the phosphorylcholine moiety via the 2-chloro-2-oxo-1,3,2-dioxaphospholane-trimethylamine sequence.The synthetic alkoxyphospholipids have been shown to exhibit potent platelet activation, antihypertensive properties, and cytotoxicity again st HL-60 cells.Microcalorimetric studies of one compound have revealed a unique phase-transition behavior resulting from the presence of the 1-alkyl rather than a 1-acyl substituent in the molecule.The synthetic method developed has a great deal of flexibility, providing a convenient general route to a wide range of ether phospholipids for physicochemical as well as enzymological studies.