Enantioselective Synthesis of 3-Arylindan-1-ones via Intramolecular C-H Insertion Reactions of α-Diazo-β-Ketoesters Catalyzed by Chiral Dirhodium(II) Carboxylates

A new, catalytic enantioselective route to 3-arylindan-1-ones, versatile intermediates for the synthesis of a number of bioactive and pharmaceutically interesting molecules, was developed by exploiting the chiral dirhodium(II) complex-catalyzed intramolecular C-H insertion reaction of α-diazo-β-ketoesters as a key step. Dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4, proved to be the catalyst of choice for this process, providing enantioselectivities of up to 72% ee

Lack of sphingosine 1-phosphate-degrading enzymes in erythrocytes

Platelets are known to store a large amount of the bioactive lipid molecule sphingosine 1-phosphate (S1P) and to release it into the plasma in a stimuli-dependent manner. Erythrocytes can also release S1P, independently from any stimuli. We measured the S1P and sphingosine (Sph) levels in erythrocytes by HPLC and found that the contribution of erythrocyte S1P to whole blood S1P levels is actually higher than that of platelets. In vitro assays demonstrated that erythrocytes possess much weaker Sph kinase activity compared to platelets but lack the S1P-degrading activities of either S1P lyase or S1P phosphohydrolase. This combination may enable erythrocytes to maintain a high S1P content relative to Sph. The absence of both S1P-degrading enzymes has not been reported for other cell types. Thus, erythrocytes may be specialized cells for storing and supplying plasma S1P

The immunomodulator FTY720 is phosphorylated and released from platelets

The novel immunomodulator FTY720 causes lymphocytes from peripheral blood to accumulate in lymphoid tissues. In vivo, FTY720 is phosphorylated to FTY720-P, which binds to the sphingosine 1-phosphate receptor S1P1. So far, it has been unclear where FTY720-P is produced. We demonstrate that platelets efficiently convert FTY720 to FTY720-P and release it into the extracellular space. This release is mostly independent of platelet activation, but is slightly increased upon thrombin stimulation. These results suggest that platelets are a major source of plasma FTY720-P, and that FTY720-P release is mediated by two different transporters