Phosphonolipids. XXIII. Synthesis of phosphonic acid analogues of L-α-(N-methyl)cephalins

A procedure for the synthesis of the racemic as well as both enantiomeric forms of phosphonic acid analogues of α-(N-methyl)cephalins has been developed. The synthesis of two representative members of a homologous series of L-α-phosphono(N-methyl)cephalins with saturated aliphatic acid substituents is described in detail. They were obtained by phosphonylating D-α,β-distearin and D-α,β-dipalmitin, respectively, with (N-carbobenzoxy,N-methyl-2-aminoethyl)phosphonic acid monochloride and tri-ethylamine, and removing the protective carbobenzoxy group of the diaeyl-L-α-glyceryl-(N-carbobenzoxy,N-methyl-2-aminoethyl)phosphonates by catalytic hydrogenolysis. The (N-carbobenzoxy,N-methyl-2-aminoethyl)phosphonic acid and its monochloride were prepared by treating the sodium salt of (N-methyl-2-aminoethyl)phosphonic acid with carbobenzoxychloride, and converting the (N-carbobenzoxy,N-methyl-2-aminoethyl)phosphonic acid to the chloride by means of phosphorus pentachloride. α-Phosphono(N-methyl)cephalins, α-(N-methyl)cephalins, and α-cehalins with identical fatty acid substituents have similar melting points, specific rotations, and solubility properties. The α-phosphono(N-ethyl)cephalins can be readily separated from α-(N-methyl)cephalins and α-cephalins by thin-layer chromatography on silica gel H or G.