Efficient Stereospecific Synthesis of Diamide Analogs of Phosphatidylcholine Starting from 1-(4′-Methoxyphenyl)-sn-glycerol

摘要

Amide analogs of diacylglycerophosphocholines are of interest as inhibitors of phospholipase A_2 and as potential anti-HIV and antitumor agents. Synthetic amide-linked lipids have been used to investigate the influence of lipid structure on lipid movement in bilayer membranes. Low-yielding achiral syntheses of 1,2-bis-(acylamino)-1,2-dideoxy-sn-glycerophosphocholine (1) have been reported starting from 2,3-dibromopropanol, 2,3-dibromopropionic acid, and L-asparagihe. We report here an efficient chiral synthesis of 1 starting from readily available 1-(4′-methoxyphenyl)-sn-glycerol (2); 2′, the enantiomer of 2, afforded 2,3-diamido-1-propanol (4c′), which can be converted into the enantiomer of 1.