Synthesis of trideuterated O-alkyl platelet activating factor and lyso derivatives.

摘要: Racemic heavy isotope analogs of 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF) and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were prepared for use as internal standards to facilitate quantitative studies based on mass spectrometry. Starting from pentadencane-1,15-diol andrac-glycerol-1,2-acetonide, a convergent synthesis 1-O-[16′-2H3]hexadecyl 1-O-[18′-2H3]octadecylrac-glycero-3-phosphocholine their acetyl derivatives is described. Three deuterium atoms introduced at the terminal position 1-O-alkyl group by displacement thep-toluensulfonyl 1-O-alkyl-15′-p-toluensulfonate 1-O-alkyl-17′-p-toluensulfonate with [2H3]-methylmagnesium iodide. The was obtained reaction allylmagnesium bromide, followed reductive ozonolysis treatment withp-toluenesulfonyl chloride. hydroxyl C-2 protected benzyl removed late stage in synthesis. This provided corresponding lysoderivatives or allowed preparation racemic PAF subsequent acetylation free hydroxy group. phosphocholine moiety glycerol C-3 bromoethyldichlorophosphate trimethylamine. synthetic compounds analyzed FAB/MS GC/NICIMS. They shown contain less than 0.6% protium impurity.