A facile regioselective synthesis of sphingosine 1-phosphate and ceramide 1-phosphate

A novel regioselective synthesis of d-erythro-sphingosine 1-phosphate and d-erythro-ceramide 1-phosphate is described. The synthesis is based upon (1) in situ oxidative phosphorylation of the primary hydroxyl group in N-Boc-d-erythro-sphingosine utilizing trimethyl phosphite and carbon tetrabromide in pyridine, (2) chemoselective deprotection of the 1-O-phosphate and/or 2-amino groups with trimethylsilyl bromide or chloride, and (3) introduction of the fatty acid moiety into sphingosine 1-phosphate dimethyl ester via base-catalyzed N-acylation.