Chemical synthesis of d-ribo-phytosphingosine-1-phosphate, a potential modulator of cellular processes

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.—Li, S., W. K. Wilson, and G. J. Schroepfer, Jr. Chemical synthesis of d-ribo-phytosphingosine-1-phosphate, a potential modulator of cellular processes. J. Lipid. Res. 1999. 40: 117–125.

Keywords

• phytosphingosine-1-phosphate
• sphingosine-1-phosphate
• phosphorylation
• NMR
• mass spectrometry