Chemical synthesis of D-ribo-phytosphingosine-1-phosphate, a potential modulator of cellular processes.
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
S
Departments of Biochemistry and Cell Biology and of Chemistry, Rice University, 6100 Main St., Houston, TX 77005-1892, USA.
Wilson
W K
WK
Schroepfer
G J
GJ
D000818:Animals; D006801:Humans; D007202:Indicators and Reagents; D008246:Lysophospholipids; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D010766:Phosphorylation; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D007202:Indicators and Reagents; D008246:Lysophospholipids; C117422:phytosphingosine-1-phosphate; C060506:sphingosine 1-phosphate; D013110:Sphingosine