An efficient route to N palmitoyl D crythro sphingomyelin and its 13C-labeled derivatives

Article abstract of DOI:10.1016/0009-3084(93)90029-3

We describe here a practical and efficient route to a homogeneous N palmitoyl D crythro sphingomyelin and its ¹³C-labeled derivatives. (2S, 3R,4E)-2-Azido-3-(tert-butyldimethylsilyloxy)-4-octadecene-l-ol1 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 3a. 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 crythro sphingomyelin 6a. The overall yield of this five-step synthesis is 43%. The melting point, 213-215°C, the specific rotation, [α]²⁰D - +6.8 (c= 1-3, CH₂Cl₂MeOH 1:1) and ¹H-and ¹³C-NMR data indicate that the synthetic sphingomyelin is enantiomerically pure. The ¹³C-labeled derivatives 6b, 6c and 6d were synthesized by employing the same scheme.