An efficient route to N-palmitoyl-D-erythro-sphingomyelin and its 13C-labeled derivatives.
We describe here a practical and efficient route to a homogeneous N-palmitoyl-D-erythro-sphingomyelin and its 13C-labeled derivatives. (2S,3R,4E)-2-Azido-3-(tert-butyldimethylsilyloxy)-4-octad ecene-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 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-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 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.
Dong
Z
Z
Clippinger Laboratories, Department of Chemistry, Ohio University, Athens 45701.
Butcher
J A
JA
D002247:Carbon Isotopes; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D009904:Optical Rotation; D013109:Sphingomyelins / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D002247:Carbon Isotopes; D007202:Indicators and Reagents; D013109:Sphingomyelins; C033171:palmitoylsphingomyelin