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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Alanine / analogs & derivatives
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Alanine / chemistry
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Ceramides / chemical synthesis*
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Ceramides / pharmacology
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Dose-Response Relationship, Drug
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Fumonisins / chemistry
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Humans
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Kinetics
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Lipids / chemical synthesis*
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Lipids / pharmacology
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Organometallic Compounds / chemistry
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Oxidoreductases / metabolism*
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Sphingosine / chemistry
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Stereoisomerism
Substances
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Antineoplastic Agents
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Ceramides
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Fumonisins
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Lipids
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Organometallic Compounds
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Schwartz reagent
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dihydroceramide
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alaninal
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Oxidoreductases
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dihydroceramide desaturase
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Sphingosine
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Alanine
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spisulosine