Phosphono-platelet activating factor. II. Synthesis of 2-acetamido-2-deoxy-1-O-octadecylglycerol-3-(2-trimethylammoniumethyl) and (2-aminoethyl)phosphonates

Abstract The chemical synthesis of the amide analogs of 1- O -alkyl-2- O -glyceryl-3- O -phosphoryl choline as its phosphono analog (phosphono-AGEPC) and 1- O -alkyl-2- O -acetyl-glyceryl-3- O -phosphoryl ethanolamine as its phosphono analog (phosphono-AGEPE) is reported. The intermediate acetamides for the subsequent phosphonylations were obtained (i) by classical organic reactions and (ii) by the method of Chandrakumar and Hadju (Tetrahedron Lett., 23 (1982) 1043–1046). Phosphonylation for the choline analog was accomplished with 2-bromoethyl phosphonic acid monochloride in anhydrous and ethanol-free chloroform in the presence of triethylamine. This was followed by reaction with anhydrous trimethylamine in dimethylformamide in a sealed tube at 50–55°C for 3 days. Phosphonylation for the ethanolamine analog was accomplished with 2-pinthalimidoethyl-phosphonic acid monochloride in anhydrous and ethanol-free chloroform in the presence of anhydrous triethylamine, followed by hydrazinolysis in 90% ethanol under reflux for 4 h. The products were identified by elemental analysis, thin-layer chromatography (TLC) and IR spectroscopy.