Triester glycerothiophosphates of cholecalciferol (vitamin D3)

Tris(N,N-dimethyl)amide of phosphorous acid activated by addition of iodine at an optimal molar ratio of 1.05∶0.05 was used as a phosphorylating reagent to synthesize cholecalciferyl-3-O-(1-2-isopropylidene-rac-glycero-3-O-)-thiophosphate and cholecalciferyl-3-O-(1,2-dipalmitoyl-rac-glycero-3-O-)thiophosphate of methyl alcohol, 2-dimethylaminoethanol, 3-dimethylamino-1-propanol and 1,2-isopropylidene-rac-glycerol in a “one-pot procedure” in overall yields of 60–80%. Activation of the reaction with an equimolar mixture of imidazoeland carbon disulfide at the triester formation step permits selective phosphorylation at room temperature. The compounds synthesized represent new triester phospholipid model compounds in which (in addition to glycerol and another requisite alcohol) a steroid and an element other than oxygen are bond to phosphorus.