EFFICIENT SYNTHESIS OF SPHINGOSINE-1-PHOSPHATE, CERAMIDE-1-PHOSPHATE,LYSOSPHINGOMYELIN, AND SPHINGOMYELIN

Readily available D-erythro-azidosphingosine is transformed into 3-O-s ilyl-protected derivative 6. Reduction of the azido group afforded 3-O -silyl-protected sphingosine 7 which was either converted into N-Fmoc- protected derivative 8 or via N-acylation into ceramide derivatives 16 and 17, respectively. Treatment of 6, 8, and 16 with bis(2-cyanoethox y)(diisopropylamino)phosphane as monofunctional phosphitylating agent, subsequent oxidation and then removal of the protective groups furnis hed azidosphingosine-1-phosphate (11), sphingosine-1-phosphate (2), an d ceramide-1-phosphate (4), respectively. Treatment of 8 and 17 with b is(diisopropylamino) (2-cyanoethoxy)phosphane as bifunctional phosphit ylating agent and then with choline afforded after oxidation and subse quent deprotection lysosphingomyelin (3) and sphingomeylin (1), respec tively in high overall yields. All final products are stereochemically pure and possess D-erythro configuration in the sphingosine moiety.