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 -ribophytosphingosine. 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.

Halisphingosines A and B, Modified Sphingoid Bases from Haliclona tubifera. Assignment of Configuration by Circular Dichroism and van’t Hoff’s Principle of Optical Superposition

“…The challenges of assignment of multiple stereocenters in acyclic natural products can be formidable . The original configurational analysis of 1 was carried out by comparison of 1 H NMR spectra of the tetra-Mosher’s ester derivative of 1 with those of the corresponding four synthetic stereoisomers of sphinganine . Although strictly not an accurate comparison ( 1 contains an additional allylic OH at C-6), the conclusion of the analysis suggested a likely match for the (2 R ,3 R ,6 R ) isomer.…”

Total Synthesis of Phospholipomannan of Candida albicans

“…Phytoceramides are widely distributed in plants, yeasts, fungi, and even in mammalian tissues and are responsible for a number of physiological processes including cell recognition, adhesion, signal transduction, apoptosis, and control of immune response . Considering their importance, several methods were reported in the literature regarding their synthesis from carbohydrates or amino acid-derived chiral starting materials, and few are based on asymmetric synthesis . However, in the present study, the A 3 coupling strategy was employed, considering its ease of operation and high enantioselectivity outcome, for the synthesis of key intermediate 13 of phytoceramide .…”

Aziridine Ring Opening for the Synthesis of Sphingolipid Analogues: Inhibitors of Sphingolipid-Metabolizing Enzymes

“…From the synthetic point of view, the phosphosphingolipids are usually obtained by direct phosphorylation of the alcohol function of ceramides in the presence of a variety of phosphorylating agents. − Alternatively, we were interested in the possible use of aziridine derivatives in the synthesis of phosphorylated sphingolipid compounds.…”

“…The synthesis of O -phosphorylated analogues based on aziridine opening is also attractive, due to their important biological properties and the limited number of methods to prepare these compounds. Literature references report the synthesis of analogues of sphingosine-1-phosphate, , ceramide-1-phosphate, , d - ribo -phytosphigosine-1-phoshate, , or l - lyxo -phytosphigosine-1-phoshate …”