The synthesis of phosphonic acid and phosphate analogues of glycerol-3-phosphate and related metabolites

A convenient route is described for the preparation of the isosteric phosphonic acid analogue of glycerol-3-phosphate, 3,4-dihydroxybutyl-1-phosphonic acid, in both enantiomeric forms and the racemic modification, starting with readily available materials. The (S)-enantiomer, that of absolute configuration corresponding to that of sn-glycerol-3-phosphate, has been found to be a growth inhibitor of several bacteria at low concentration. The synthetic route described is of particular value as it facilitates the preparation of a series of phosphonic adds and phosphates of related structure, in their enantiomeric forms, which are also of interest for metabolic regulation. These include the 3,4-epoxybutyl-1-phosphonate and a phosphate analogue of glycerol-3-phosphate with the related homodiglyceride. Investigations are continuing in the evaluation of the biological activity of the materials synthesized. A method is also described for the synthesis of the carbon-14 labelled 3-carboxy-3-hydroxybutyl-1-phosphonic acid, an analogue of phosphoglyceric acid known to serve as a substitute for the natural material in several biochemical processes.