posted on 2013-06-21, 00:00authored byJosé Luis Abad, Ingrid Nieves, Pedro Rayo, Josefina Casas, Gemma Fabriàs, Antonio Delgado
A stereoselective
synthesis of spisulosine (ES285)
and 4,5-dehydrospisulosine stereoisomers is described. Hydrozirconation
of 1-pentadecyne with Schwartz reagent, followed by diastereocontrolled
addition to l- or d-alaninal afforded the required
2-amino-1,3-diol framework. The resulting sphingoid bases revealed
as excellent probes for the profiling of ceramide synthase activity
in intact cells. Among the sphingoid bases described in this work,
spisulosine (ES285), RBM1-77, and RBM1-73 were the most suitable ones because of their highest
acylation rates. These molecules should prove useful to study the
role of the different ceramide synthases and the resulting N-acyl (dihydro)ceramides in cell fate.