Ruthenium Olefin Metathesis Catalysts Bearing a Macrocyclic N-Heterocyclic Carbene Ligand: Improved Stability and Activity.

Formation of sterically hindered C-C double bonds via catalytic olefin metathesis is considered a very challenging task for Ru catalysts. This limitation led to the development of specialised catalysts bearing sterically reduced N-heterocyclic carbene (NHC) ligands that are very active in such transformations, yet significantly less stable as compared to general purpose catalysts. To decrease the small-size NHC catalysts susceptibility to decomposition, a new NHC ligand was designed, in which two sterically reduced aryl arms were tied together by a C-8 alkyl chain.

Total synthesis of ezetimibe, a cholesterol absorption inhibitor.

Ezetimibe (1), a strong β-lactamic cholesterol absorption inhibitor, was synthesized from (R)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one 7. Independent pathways were analyzed in order to select the optimal one, which involved 1,3-dipolar cycloaddition with C-(4-benzyloxyphenyl)-N-(4-fluorophenyl)-nitrone (8), intramolecular nucleophilic displacement at the benzylic position of the lactone, cleavage of the N-O bond, elimination of a water molecule, hydrogenation of the double bond, rearrangement of the six-membered lactone ring into a β-lactam moiety, and final deprotection of the phenolic hydroxyl group. Highly stereoselective Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition was the most crucial step of the synthesis.

Computerised controllers for safety critical medical applications.

A novel design for a computer control system to be employed in safety critical applications, as found in medical environments, is presented. It features a low complexity, fault detecting hardware architecturally supporting a strictly cyclic operating mode, as known from programmable logic controllers, and a specification level, graphical programming technique based on the interconnection of application oriented standard software function modules. By design, there is no semantic gap between the programming and machine execution levels.

Responses to calcium and binding of 3H-nimodipine in the atrioventricular node, atria, and ventricles of mature and old male Fischer 344 rats.

To determine whether aging alters cardiac calcium dose responses or dihydropyridine receptor density or affinity, we performed (a) calcium (Ca2+) dose-response studies (3-5 mM) in Langendorff perfused hearts from 12 mature (4-7 month) and 12 old (23-27 month) Fischer 344 rats, and (b) quantitative autoradiography experiments with 3H-nimodipine (50-3,000 pM) in 20-microns tissue sections containing the compact AV node from hearts of eight mature and eight old F344 rats. Baseline AA interval, AV conduction time, AV Wenckebach block cycle length, and QRS duration were prolonged in isolated hearts from old compared with mature rats. In contrast, neither left ventricular developed pressure nor peak dP/dt was altered by age.

Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle.

Background: Age-related differences in responses to verapamil have been noted in both intact humans and isolated denervated perfused rat hearts. The study was designed to determine the effects of aging on intracardiac conduction and pharmacodynamic responses to verapamil, and also to determine the potential role of autonomic responses in previously reported age-related differences in responses to verapamil.

Methods: After stability of measures was demonstrated in senescent animals, nine young (aged 3-4 years: 12.