Preparation of phosphoglycerides by phosphoramidite chemistry

Abstract

Phosphoglycerides have been prepared in high yield by a three-step procedure utilising phosphoramidite intermediates. 2-Chloro-3-methyl-1,3,2-oxazaphosphospholidine 5 reacts with diacylglycerols to give cyclic phosphoramidites in near-quantitative yield. These are oxidised to the corresponding phosphates in very high yield with N₂O₄. The phosphates hydrolyse in water at ambient temperature, via exclusive P–N cleavage, to yield the target phospholipids. Similarly prepared from 2-chloro-1,3-dimethyl-1,3,2-diazaphospholidine 1 were the phosphoramidate lipid analogues. Spectral data on the intermediates and products are included and discussed.