piperidines and malonic-acid

We have investigated important intermediates and key transition states of the organocatalyzed Knoevenagel condensation using density functional theory and two different basis sets (6-31 G(d,p) and 6-311++G(2df,2pd)), both in gas phase and simulating the bulk solvent (pyridine) using the PCM method. Calculated structures for reactants, intermediates, and key transition states suggest that the secondary amine catalyst is essential, both for activating the aldehyde for nucleophilic attack, and in the possible decarboxylation pathways. The calculated results are shown to agree with available experimental information. On the basis of the results obtained, the studied mechanism may be important in the understanding of vinylphenol production during malting and brewing of wheat and barley grains.

Topics: Benzaldehydes; Beverages; Carboxylic Acids; Catalysis; Food; Malonates; Models, Molecular; Molecular Conformation; Phenols; Piperidines; Proline; Quantum Theory; Solvents

Cannabinoids could provide neuroprotection in neurodegenerative disorders. In this study, we examined whether a treatment with Delta9-tetrahydrocannabinol, a non-selective cannabinoid receptor agonist, or with SR141716, a selective antagonist for the cannabinoid CB(1) receptor subtype, could affect the toxicity of the complex II reversible inhibitor malonate injected into the striatum, which replicates the mitochondrial complex II deficiency seen in Huntington's disease patients. As expected, malonate injection produced a significant reduction in cytochrome oxidase activity in the striatum consistent with the expected neurodegeneration caused by this toxin. The administration of Delta9-tetrahydrocannabinol increased malonate-induced striatal lesions compared to vehicle and, surprisingly, SR141716, far from producing effects opposite to those of Delta9-tetrahydrocannabinol, also enhanced malonate effects, and to an even greater extent. In summary, our results are compatible with the idea that manipulating the endocannabinoid system can modify neurodegeneration in Huntington's disease, and suggest that highly selective CB(1) receptor agonists might be necessary to produce neuroprotective effects against indirect excitotoxicity.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Corpus Striatum; Disease Models, Animal; Dronabinol; Electron Transport Complex II; Enzyme Inhibitors; Huntington Disease; Male; Malonates; Multienzyme Complexes; Oxidoreductases; Piperidines; Psychotropic Drugs; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug; Rimonabant; Succinate Dehydrogenase