Synthesis of Glycerol-1,3-diphosphonic Acid

The synthesis of glycerol-1,3-diphosphonic acid, the phosphonic acid analogue of the naturally occurring glycerol-1,3-diphosphoric acid, is described. The phosphonic acid analogue was obtained in an overall yield of 29.7%, by heating a mixture of 1,3-dibromo-2-hexadecanoyloxypropane and triethyl phosphite to 140° for 48 h, distilling off in vacuo the excess of triethyl phosphite, hydrolyzing the condensation product, 1,3-bis(diethylphosphono)-2-hexadecanoyloxypropane, with 2 N hydrobromic acid at 100° for 5 h, and isolating the glycerol-1,3-diphosphonic acid in form of the dibarium salt. The glycerol-1,3-diphosphonate differs from glycerol-1,3-diphosphate and other phosphate esters of glycerol and glyceric acid by its greater stability towards acid hydrolysis. The glycerol-1,3-diphosphonic acid is readily distinguished from glycerol-1,3-diphosphoric acid and glycerol-1,2-diphosphoric acid by paper chromatography.