title: Straightforward access to spisulosine and 4,5-dehydrospisulosine stereoisomers: probes for profiling ceramide synthase activities in intact cells.
abstract: 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.
authors.affiliation: 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. jlaqob@cid.csic.es
authors.forename: José Luis
authors.initials: JL
authors.lastname: Abad
authors.forename: Ingrid
authors.initials: I
authors.lastname: Nieves
authors.forename: Pedro
authors.initials: P
authors.lastname: Rayo
authors.forename: Josefina
authors.initials: J
authors.lastname: Casas
authors.forename: Gemma
authors.initials: G
authors.lastname: Fabriàs
authors.forename: Antonio
authors.initials: A
authors.lastname: Delgado
mesh_terms: D000215:Acylation; D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D037341:Fumonisins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000138:chemical synthesis* / Q000494:pharmacology; D009942:Organometallic Compounds / Q000737:chemistry; D010088:Oxidoreductases / Q000378:metabolism*; D013110:Sphingosine / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D037341:Fumonisins; D008055:Lipids; D009942:Organometallic Compounds; C532427:Schwartz reagent; C109343:dihydroceramide; C046025:alaninal; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D013110:Sphingosine; D000409:Alanine; C408363:spisulosine