Synthesis of enzyme-inhibitory phospholipid analogs. III. A facile synthesis of N-acylaminoethylphosphorylcholines.
A facile and efficient synthesis of N-aceylaminoethylphosphorylcholines, a series of inhibitory substrate analogs of phospholipase A2, is described. The procedure consists of a three-step sequence including: (1) N-acylation of ethanolamine with fatty acid chloride, followed by (2) phosphorylation of the alcohol function using 2-chloro-2-oxo-1,3,2-dioxaphospholane and (3) nucleophilic ring opening of the cyclic phosphate triester (IV) with anhydrous trimethylamine. The resulting isosteric amide analogs of glycol-lecithins have been isolated in high yields. The synthesis is illustrated by the preparation of the compounds containing palmitoyl, stearoyl and lauroyl fatty acid side-chains. The N-acylaminoethylphosphorylcholines have been shown to function as reversible phospholipase A2 inhibitors. They are likely to become a new series of useful substrate analogs and an attractive replacement for the n-alkylphosphorylcholines commonly used as single-chain-carrying phospholipase inhibitors.
D055598:Chemical Phenomena; D002621:Chemistry; D002794:Choline / Q000031:analogs & derivatives*; D010713:Phosphatidylcholines; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D010713:Phosphatidylcholines; D010767:Phosphorylcholine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002794:Choline