Consejo Superior de Investigaciones Científicas (CSIC), Institut de Química Avançada de Catalunya (IQAC-CSIC), Research Unit on Bioactive Molecules (RUBAM), Jordi Girona 18-26, 08034 Barcelona, Spain.
J Org Chem. 2013 Jun 21;78(12):5858-66. doi: 10.1021/jo400440z. Epub 2013 May 30.
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.
本文描述了（ES285）螺甾辛因和 4,5-脱氢螺甾辛因立体异构体的立体选择性合成。施瓦茨试剂对 1-十五碳炔的氢锆化反应，随后与 L-或 D-丙氨酸进行非对映选择性加成，得到所需的 2-氨基-1,3-二醇骨架。所得的神经鞘氨醇碱基是研究完整细胞中神经酰胺合酶活性的极好探针。在本工作中描述的神经鞘氨醇碱基中，螺甾辛因（ES285）、RBM1-77 和 RBM1-73 是最合适的，因为它们的酰化率最高。这些分子应该有助于研究不同的神经酰胺合酶的作用以及由此产生的 N-酰基（二氢）神经酰胺在细胞命运中的作用。
