[The hepatopulmonary syndrome]. / Le syndrome hépatopulmonaire.

DEFINITION: The hepatopulmonary syndrome (HPS) associates a chronic hepatic affection, hypoxemia < 70 mm Hg and pulmonary vasodilatation. PHYSIOPATHOLOGY: The mechanisms leading to pulmonary vasodilatation are complex and unclear. There appears to be an imbalance between the vasodilatating and vasoconstricting mediators. Nitrogen monoxide and endotheline-1 are well known. Hypoxia can be explained by the association of heterogenic ventilation-perfusion, shunts (rare), and a default in "diffusion-perfusion". CLINICAL ASPECTS: In a hypoxic patient, platypnoea and orthodeoxia are characteristic of HPS. Stellar angioma associated with digital hippocratism and signs of portal hypertension are usually present. TO PERMIT DIAGNOSIS: The air of blood gases, followed by 100% O2, standing and reclining, must be measured in all cirrhotic patients to detect hypoxemia. Contract sonography is the key diagnostic examination. Pulmonary perfusion scintigraphy establishes prognosis. Pulmonary angiography differentiates two groups of patients and, for type II patients, embolization therapy can be proposed. Preliminary data indicate that densitometry, conducted in rigorous conditions, can show pulmonary vasodilatation. Its interest must be confirmed by further studies on larger cohorts of patients. THERAPEUTIC POSSIBILITIES: The only efficient treatment of HPS is hepatic transplant (HT). The placing of an intra-hepatic portal systemic shunt can be proposed while waiting for HT, or in certain patients not requiring HT. No medical treatment has demonstrated its efficacy, but better knowledge of the physio-pathologic mechanisms should improve this situation in the future.

Discovery of a new efficient chiral ligand for copper-catalyzed enantioselective Michael additions by high-throughput screening of a parallel library.

A combinatorial library of 125 chiral Schiff base ligands 5 was synthesized with the use of solution-phase parallel synthesis and solid-phase extraction (SPE) techniques to scavenge excess reagents and reaction by-products and avoid chromatography. The synthetic methodology coupled five N-Boc-protected beta-amino sulfonyl chlorides 1a-e with five different amines 2f-j to give 25 N-Boc sulfonamides 3, which were in turn deprotected and coupled with five salicylaldehydes 4p-t to give 125 ligands 5 in good yields and of sufficient purity to be used in ligand-catalyzed reactions. These ligands were tested in the copper-catalyzed conjugate addition of dialkyl zinc to cyclic and acyclic enones. A multisubstrate high-throughput screening of the library was performed with an equimolar mixture of 2-cyclohexenone and 2-cycloheptenone (9 and 10, respectively, 0.2 mmol total), with 5.5 mol% ligand 5 (0.011 mmol) and 5 mol% Cu(OTf)2 (OTf= OSO2CF3) (0.010 mmol) in 1:1 toluene/ hexane at - 20 degrees C. From the screening of the library, 5bhr was identified as the best ligand, which yielded 3-ethylcyclohexanone (12) and 3-ethylcycloheptanone (13) in 82% and 81% ee, respectively, and complete conversions. Under optimized conditions (2.75 mol% 5bhr, 2.5 mol% copper(i) triflate, toluene as reaction solvent), improved results were obtained for 12 (90% ee, 93% yield) and for 13 (91% ee, 95% yield). Selected ligands 5 were also tested in the addition of Me2Zn to 2-cyclohexenone (9, ee up to 79%), of Et2Zn to 2-cyclopentenone (11, ee up to 80%) and to acyclic enones 16 and 17 (ee up to 50%).

Activation of the dienophilicity of indoles in normal electron demand [4 + 2] cycloadditions under high pressure.

[reaction: see Text] Activation by either high pressure or a combination of Lewis acid catalysis and high pressure allows indole derivatives to behave as dienophiles in [4 + 2] cycloaddition reactions under mild conditions. The biactivation mode has the highest impact on the stereoselectivity of the reaction. The cycloadducts resulting from these reactions are characterized by boat-shape conformations that bear well-defined orthogonal planes.