A General Synthetic Route for Preparing Ether Phospholipids Suitable for Immobilization: A Phosphotriester Approach

Article abstract of DOI:10.1021/jo00082a009

A synthetic route was developed to prepare ether phospholipid (PL) ligands suitable for immobilization.PL ligand design included an ω-carboxyl functional group to assure proper molecular orientation during immobilization; i.e., the polar lipid head group protrudes from the surface.However, during immobilization, PL ligands required protecting groups to eliminate the possibility of the PL binding upside down.Four synthetic PL ligands were prepared that contain both ω-carboxyl groups for immobilization and protecting groups in the polar head group; these carboxyl-PLligands are analogs of phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), and phosphatidic acid (PA).The critical synthetic step during PL synthesis is the phosphorylation step which usually has the lowest yield of all other steps.This is the first report demonstrating that o-chlorophenyl dichloro phosphate (CPDCP) can be used as a mild phosphorylation reagent for the preparation of PL analogs.Phosphorylation with CPDCP is routinely 50-90percent efficient depending on the analog, but more important is that the protecting groups associated with PE, PS, PG, and PA are stable during this critical synthetic step.After immobilization of the carboxyl-PL ligands, acidic or basic solution conditions are needed for deprotection and generation of free PE, PG, PS, and PA polar lipid head groups which protrude from the surface.This work demonstrates that CPDCP is an excellent synthetic reagent for all ether PL analogs either with or without ω-carboxyl functional groups.