N-Acetyl-L-threo-sphingosine

This non-natural L-threo-ceramide contains an acetyl group which allows it to enter easily into cells where it demonstrates activity different from natural D-erythro-ceramides. N-Acetyl-threo-sphingosine can be converted to the N-acetyl-threosphingosylphosphorylcholine in the presence of Mn2+ and CDP-choline.1 Glucosyl-N-acetyl-L-threo-sphingosine was found to be a poorer substrate for beta-glucosidase than the D-erythro isomer but was able to undergo cleavage.2 N-Acetyl-Derythro- sphingosine demonstrates many of the biological activities associated with ceramides that contain long-chain fatty acids. However, it has also been found that this N-acetyl-sphingosine may inhibit neutrophil superoxide release,3 stimulation of DNA synthesis, and phospholipase D activity. N-acetyl-D-erythro-sphingosine is different from sphingosine as seen by its inability to inhibit protein kinase C or cause calcium release. Ceramide is a fatty acid amide of sphingosine that has many important biological functions and is the precursor for many complex glycosphingolipids. Ceramide functions as a precursor in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. Ceramide has been investigated for its use in cancer treatment and many potential approaches to cancer therapy have been presented.4