Straightforward Access to Spisulosine and 4,5-Dehydrospisulosine Stereoisomers: Probes for Profiling Ceramide Synthase Activities in Intact Cells

详细信息    查看全文

• 作者：Jos茅 Luis Abad ; Ingrid Nieves ; Pedro Rayo ; Josefina Casas ; Gemma Fabri脿s ; Antonio Delgado
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：June 21, 2013
• 年：2013
• 卷：78
• 期：12
• 页码：5858-5866
• 全文大小：490K
• 年卷期：v.78,no.12(June 21, 2013)
• ISSN：1520-6904

文摘

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.