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We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.

Rhodium and iridium complexes of chiral NHC-phenolimine and NHC-amine ligands have been prepared and studied for asymmetric transfer hydrogenation. X-ray and NMR spectroscopy show that for NHC-phenolimine complexes abstraction of chloride results in a change in ligand coordination from NHC only to chelating NHC-imine. Complexes of NHC-amines are inactive for transfer hydrogenation, whereas complexes of NHC-phenolimines are active at room temperature for a range of aryl containing ketones. Enantioselectivity is very sensitive to the NHC N-substituent resulting in a switch in the predominant enantiomer.

Reactions between imidazolium-imine salts and base result in C-C bond formation via intermediate N-heterocyclic carbenes. In the presence of a proximal OH moiety, carbene formation occurs via intramolecular deprotonation by phenoxide. For simple imines, a reactive Breslow-type intermediate gives access to new heterocycles with the formation of six- and seven-member rings.

Lecithin: Cholesterol acyltransferase (LCAT) activity was measured in serum and liver tissue from patients with parenchymal liver disease. Serum LCAT activity was within normal limits and it was probably related to the absence of clinical and laboratory evidence of a decompensated liver function. Liver tissue LCAT activity is about tenfold lower than that in serum. The relative proportion of cholesterol esters in liver tissue was much higher that could be expected according the low tissue LCAT activity. This findings suggest that LCAT is a "plasma specific" enzyme and that cholesterol esters in parenchyma may be considered as a storage form of cholesterol esterified in plasma pool.

Serum lipoprotein-X was investigated in 12 patients with cholestasis in basal conditions and 20 minutes after intravenous heparin. In all cases, lipoprotein-X was positive in the first sample and became negative after heparin. A decrease in triglycerides was observed in all patients after heparin with an increase in free fatty acids and mobilization of prebetalipoproteins, and a transformation of lecithin into lysoleithin in 4 cases after heparin. These facts suggest that heparin plays an important role in the mobilization of serum lipoprotein-X.

The in vitro effect of post-heparin and post-heparin plus post-protamine normal serum on serum lipoprotein X (LP-X) is described. Serum LP-X is cleared after incubation with post-heparin normal serum, and serum LP-X remain unmodified when it is incubated with post-heparin plus post-protamine normal serum. The action of phospholipase A from snake venom on serum LP-X is also studied. A very small quantity of phospholipase is necessary to degrade LP-X and to transform lecithin into lysolecithin. It is concluded that phospholipase seems to be the enzyme that most likely induces the LP-X changes after heparin administration.