Abstract
d-erythro -Sphingosine-1-phosphate (2), an intermediate in sphingosine metabolism, shows a diversity of biological activities. Comparable roles might be anticipated for d-ribo -phytosphingosine-1-phosphate (1). We describe an efficient three-step chemical synthesis of 1 from d-ribo -phytosphingosine. Our approach is based on standard phosphoramidite methodology and on the finding of Boumendjel and Miller ( J. Lipid Res. 1994. 35: 2305-2311) that sphingosine can be monophosphorylated at the 1-hydroxyl without protection of the 3-hydroxyl. However, we were unable to duplicate their reported synthesis of 2 without important modifications in reagents and reaction conditions. Under the reported conditions for preparing 2, we obtained a cyclic carbamate (14), which we have isolated and identified. The structures of 1 and the cyclic carbamate 14 were elucidated by a combination of mass spectrometry and 1D and 2D nuclear magnetic resonance spectroscopy.
Highlights
D-erythro-Sphingosine-1-phosphate (2), an intermediate in sphingosine metabolism, shows a diversity of biological activities
Whereas almost all investigations of the formation, metabolism, and actions of the phosphate derivatives of sphingoid long-chain bases (LCB) have concerned sphingosine, essentially nothing is known of the properties and actions of the 1-phosphate derivative of another major LCB of eukaryotes, i.e., phytosphingosine
We report the first chemical synthesis and characterization of d-ribo -phytosphingosine-1-phosphate
Summary
D-erythro-Sphingosine-1-phosphate (2), an intermediate in sphingosine metabolism, shows a diversity of biological activities. We report the first chemical synthesis and characterization of d-ribo -phytosphingosine-1-phosphate.. In the present manuscript we present important improvements in a previously described chemical synthesis of sphingosine-1-phosphate (26, 27). Among many fascinating reports in the last 2 years alone have been the purification, to apparent homogeneity, of sphingosine kinase from rat kidney (6), reports on the levels of sphingosine-1-phosphate in various tissues (7) and in human plasma and serum (8), interesting studies of factors affecting sphingosine kinase activity (9–11), identification of the genes for sphingosine phosphate lyase (12) and dihydrosphingosine-1-phosphate phosphatase (13), an important report indicating high affinity binding of sphingosine-1-phosphate to the orphan receptor EDG-1 (14), and many other reports of interesting, diverse biological activities of sphingosine-1-phosphate. Earlier important actions of sphingosine-1-phosphate have been reviewed by EXPERIMENTAL PROCEDURES AND RESULTS
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