Sphingosine-type

The presence of 2-hydroxylated fatty acids can be easily determined by C NMR spectroscopy in cerebrosides containing sphingosine-type bases due to the chemical shift of C-2 (72.5 ppm). In cerebrosides with phytosphingosine-type bases, C-4 in the long-chain base and C-2 hydroxy-lated in the fatty acid moiety show similar chemical shifts [6]. 

Recently, three homogeneous sphingosine-type glucocerebrosides were isolated from the body walls of the cold water sea cucumber C. frondosa. These glucosylceramides have been previously isolated from the sea cucumbers C. echinata and S. japonicus [34],... 

Two new sphingosine-type glucocerebrosides, sarcoehrenosides A (69) and B (70), were isolated from the alcyonacean soft coral S. ehrenbergi (Fig. 19) [28]. Compound A differs from previously known marine cerebrosides in that it possesses a rare a-D-glucose moiety. Both compounds, together with four known glucocerebrosides isolated from the same coral, were evaluated for antimicrobial activity against a small panel of five bacterial strains. None of the compounds exhibited antibacterial activity at a concentration of 100 pg/disk. 

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

Fig. 14.—Schematic Representation of the Fragmentation Observed in the Positive F.a.b.-Mass Spectrum of a Permethylated Ganglioside Isolated from Granulocytes. [Other glyco-sphingolipids fragment in a similar way. Major cleavages are shown with solid lines, and minor cleavages with dotted lines. The masses of ions resulting from cleavages (a), (b), and (c) define the type of sphingosine and the type of fatty acid. In this example, (a) is 548, (b) is [M + H] minus 238, and (c) is [M + H] minus 533.]...

The transformation of the cyano group could also introduce a new chiral center under diastereoselective control (Figure 5.13). Grignard-transimination-reduction sequences have been employed in a synthesis of heterocyclic analogues of ephedrine [81]. The preferential formation of erythro-/3-amino alcohols may be explained by preferential hydride attack on the less-hindered face of the intermediate imine [82], and hydrocyanation of the imine would also appear to proceed via the same type of transition state. In the case of a,/3-unsaturated systems, reduction- transimination-reduction may be followed by protection of the /3-amino alcohol to an oxazolidinone, ozonolysis with oxidative workup, and alkali hydrolysis to give a-hydroxy-/3-amino acids [83]. This method has been successfully employed in the synthesis L-threo-sphingosine [84]. 

This method has been applied in the enantioselective synthesis of d-erythro-sphingosine and phytosphingosine. Sphingosine became an important substance for studying signal transduction since the discovery of protein kinase C inhibition by this compound.48 Many efforts have been made to synthesize sphingosine and its derivatives.49 Kobayashi et al. reported another route to this type of compound in which a Lewis acid-catalyzed asymmetric aldol reaction was a key step. 

Sphingosine 1-Phosphate Type 1 Receptor Modulators Recent Advances and Therapeutic Potential... 

The effect of sphingosine on other enzymes may also contribute to its apoptotic effect. These include the inhibition of calcium/calmodulin-requiring enzymes and DNA primase and the stimulation of casein kinase II and several unidentified kinases (Alessenko, 2000). In addition, sphingosine can increase the cellular concentration of cyclic AMP, which is inhibitory for proliferation in many cell types (Pyne and Pyne, 1996). 

Ishizuka, T., Murata, N., Kanda, T., Kobayashi, I., Ohta, H., Ui, M. and Okajima, F., 1999, Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor sub-types to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells. J. Biol. Chem. 274 23940-23947. 

T. and Spiegel, S., 2000, Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform, J. Biol. Chem. 275 19513-19520. 

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