AN EFFICIENT ROUTE TO N-PALMITOYL-D-ERYTHRO-SPHINGOMYELIN AND ITS C-13-LABELED DERIVATIVES

We describe here a practical and efficient route to a homogeneous N-palmitoyl-D-erythro-sphingomyelin and its C-13-labeled derivatives. (2S,3R,4E)-2-Azido-3-(tert-butyldimethylsilyloxy)-4-octadecene-1-ol 1 was converted to the sphingosine equivalent 2 by treatment with triphenylphosphine and water. Amine 2 was then coupled with palmitic acid, affording the ceramide derivative 39. In the following two reactions the phosphorylcholine functional group was generated by using 2-chloro-2-oxo-1,3,2-dioxaphospholane and trimethylamine, respectively. The final deprotection of the secondary hydroxyl group in 5a produced the desired N-palmitoyl-D-erythro-sphingomyelin 6a. The overall yield of this five-step synthesis is 43%. The melting point, 213-215-degrees-C, the specific rotation, [alpha]20D = +6.8 (c = 1.3, CH2Cl2/MeOH 1:1) and H-1- and C-13-NMR data indicate that the synthetic sphingomyelin is enantiomerically pure. The C-13-labeled derivatives 6b, 6c and 6d were synthesized by employing the same scheme.