NOVEL ORGANIC SYNTHESIS USING DBU (10) SYNTHESIS …

The venerable drug theophylline has been used to treat asthmatic attacks for many years. Research on the mechanism of action of this purine led to the discovery that it acted by blocking the action of the enzyme phosphodiesterase (PDE). The clinical utility of this compound pointed to the potential of PDE inhibitors as a source for new drugs. Modern methodology has led to the subdivision of PDE receptors into a number of subtypes, each of which seems to be involved in the regulation of a discrete organ system. It is of interest that a newly developed PDE inhibitor, in this case specific for PDE 4, has shown clinical activity in alleviating the symptoms of chronic obstructive pulmonary disease. This finding of course involves the same organ that led to the discovery of the field many decades ago. The first sequence in the synthesis of this new PDE inhibitor comprises homologation of the benzaldehyde (54) to phenylacetonitrile (56). Reduction of the aldehyde in the presence of lithium bromide gives the corresponding benzyl bromide; displacement of halogen by reaction with potassium cyanide gives the substituted acetonitrile (56). Condensation of that intermediate with ethyl acrylate in the presence of base leads to Michael addition of two molecules of the acrylate and formation of the diester (57). Treatment of this last intermediate with strong base leads to internal Claisen condensation with consequent formation of the carberthoxycyclohexanone derivative 58. Heating the ketoester with acid initially leads to hydrolysis of the ester to an acid. This decarboxylates under reaction conditions to give the cyclohexanone (59). Condensation of the ring carbonyl group in this intermediate with the anion from 1,3-dithiane leads to 60, in what in effect comprises addition

Organic reaction; Organic synthesis; Peptide synthesis; ..

The radiotracer chemistry group at Brookhaven National Laboratory has developed a method to directly label carbamate-containing compounds with [11C]-carbon dioxide. The new method provides a simple and accessible route to labeling compounds important in many areas of biology and will have an immediate enabling impact on the synthesis of radiotracers for applications in energy, health, and environmental research. The new approach, just published in , is based on direct CO2 fixation mediated by a nitrogen-containing organic base (DBU), which serves a dual role as a catalyst. Synthesis with carbon-11 must be incredibly fast due to its 20-minute half life. In this new method, the entire labeling process is accomplished in under 10 minutes and does not require new equipment or exotic reagents.


Reagents for organic synthesis; Tetrahydrodiazines; Navigation menu

Encyclopedia of Reagents for Organic Synthesis - Revolvy

Usage:it can replace the common reagents used in organic alkali dehydrohalogenation and be widely used in organic synthesis and antibiotic semi-synthesis.