Synthesis of 7‐Oxasphingosine and ‐ceramide Analogues and Their Evaluation in a Model for Apoptosis

The 7‐oxasphingosine ( 1 ), 7‐oxaceramide ( 2 ), the thio‐oxaceramide 3 , and N ‐methyloxaceramide 4 were synthesised from D ‐galactose via the building block 9 . The apoptosis‐inducing properties of 1 – 4 were compared to those of sphingosine (Sph) and ceramide (Cer) using a human neuroblastoma (SK‐N‐BE) and a murine‐promyelocyte‐derived (32d) cell line. There were no differences between 2 – 4 and Cer in terms of their effects on the viability of cells and their ability to trigger cell proliferation. However, in the presence of N , N ‐dimethylsphingosine, an inhibitor of sphingosine kinase (SPHK), Cer was more potent than thio‐ceramide 3 in 32d cells, while thio‐ceramide 3 was more potent and efficacious in SK‐N‐BE cells, where it showed an IC 50 value of 3 n M compared to 100 n M for Cer. In both SK‐N‐BE and 32d cells, 7‐oxasphingosine ( 1 ) and Sph were equally toxic, even in the presence of N , N ‐dimethylsphingosine.