Synthesis of chiral amino cyclic phosphoric acids
Chiral amino cyclic phosphoric acids, 5-amino-2-hydroxy-4-(4-nitrophenyl)-1,3,2-dioxaphosphorinane 2-oxide and 2-hydroxy-4-(4-methylsulfonylphenyl)-5-phthalimido-1,3,2-dioxaphos phorinane 2-oxide are synthesized in good over yields (64.2% and 72.8% respectively) from 2-amino-1-aryl-1,3-propanediols. The different reaction conditions are necessary in hydrolysis reactions of amino cyclic phosphonyl chlorides.
SYNTHESIS OF CYCLIC SPHINGOSINE 1,3-PHOSPHATE (CSPP) THROUGH A PHOTOLYTIC REACTION
Abstract The synthesis of cyclic sphingosine 1,3-phosphate through photolytic methodology is described starting from d - erythro -sphingosine. A bifunctional phosphorylating reagent, 2-cyanoethyl N,N -diisopropylchlorophosphoramidite, is used to introduce the cyclic 1,3-phosphate moiety. This procedure generates cSPP in four steps and in 36% overall yield.
Involvement of a Pertussis Toxin-sensitive G Protein in the Mitogenic Signaling Pathways of Sphingosine 1-Phosphate (*)
Sphingosine 1-phosphate, a sphingolipid metabolite, was previously reported to increase DNA synthesis in quiescent Swiss 3T3 fibroblasts and to induce transient increases in intracellular free calcium (Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell Biol. 114, 155-167). In the present study, pretreatment of Swiss 3T3 fibroblasts with pertussis toxin reduced sphingosine 1-phosphate-induced DNA synthesis. Sphingosine 1-phosphate decreased cellular cAMP levels and also caused a drastic decrease in isoproterenol- and forskolin-stimulated cAMP accumulation. Pertussis toxin treatment prevented the inhibitory effect of sphingosine 1-phosphate on cAMP accumulation, suggesting that a pertussis toxin-sensitive Gior Gi-like protein may be involved in sphingosine 1-phosphate-mediated inhibition of cAMP accumulation. Mitogenic concentrations of sphingosine 1-phosphate stimulated production of inositol phosphates which was inhibited by pertussis toxin, while the response to bradykinin was not affected. Furthermore, calcium release induced by sphingosine 1-phosphate, but not by bradykinin, was also attenuated by pertussis toxin treatment. However, sphingosine 1-phosphate-induced phosphatidic acid accumulation was unaffected by pertussis toxin. The increase in specific DNA binding activity of activator protein-1, which was induced by treatment of quiescent Swiss 3T3 fibroblasts with sphingosine 1-phosphate, was also inhibited by pertussis toxin. These results suggest that some of the sphingosine 1-phosphate-induced signaling pathways are mediated by G proteins that are substrates for pertussis toxin.