5579-73-7Relevant articles and documents
Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2-diones
Parkinson, Elizabeth I.,Jason Hatfield,Tsurkan, Lyudmila,Hyatt, Janice L.,Edwards, Carol C.,Hicks, Latorya D.,Yan, Bing,Potter, Philip M.
experimental part, p. 4635 - 4643 (2011/09/19)
Carboxylesterases (CE) are ubiquitous enzymes found in both human and animal tissues and are responsible for the metabolism of xenobiotics. This includes numerous natural products, as well as a many clinically used drugs. Hence, the activity of these agents is likely dependent upon the levels and location of CE expression. We have recently identified benzil is a potent inhibitor of mammalian CEs, and in this study, we have assessed the ability of analogues of this compound to inhibit these enzymes. Three different classes of molecules were assayed: One containing different atoms vicinal to the carbonyl carbon atom and the benzene ring [PhXC(O)C(O)XPh, where X = CH2, CHBr, N, S, or O]; a second containing a panel of alkyl 1,2-diones demonstrating increasing alkyl chain length; and a third consisting of a series of 1-phenyl-2-alkyl-1,2-diones. In general, with the former series of molecules, heteroatoms resulted in either loss of inhibitory potency (when X = N), or conversion of the compounds into substrates for the enzymes (when X = S or O). However, the inclusion of a brominated methylene atom resulted in potent CE inhibition. Subsequent analysis with the alkyl diones [RC(O)C(O)R, where R ranged from CH3 to C8H17] and 1-phenyl-2-alkyl-1,2-diones [PhC(O)C(O)R where R ranged from CH3 to C6H13], demonstrated that the potency of enzyme inhibition directly correlated with the hydrophobicity (c log P) of the molecules. We conclude from these studies that that the inhibitory power of these 1,2-dione derivatives depends primarily upon the hydrophobicity of the R group, but also on the electrophilicity of the carbonyl group.
Samarium diiodide promoted formation of 1,2-diketones and 1-acylamido-2-substituted benzimidazoles from N-acylbenzotriazoles
Wang, Xiaoxia,Zhang, Yongmin
, p. 4201 - 4207 (2007/10/03)
N-Acylbenzotriazoles, when treated with samarium diiodide in THF, undergo self-coupling reaction to afford 1,2-diketones in good to excellent yields; while when treated with samarium diiodide in CH3CN, they undergo ring-opening reaction to afford 1-acylamido-2-alkyl (or aryl) benzimidazoles in reasonable to good yields. A plausible mechanism was suggested.
Difluoroboroxymolybdenum fischer carbene complexes as precursors of acyl radicals: Dimerization and trapping with electron-deficient alkenes
Barluenga, Jose,Rodriguez, Felix,Fananas, Francisco J.
, p. 1930 - 1937 (2007/10/03)
Pentacarbonyl acyl molybdates 1 react with boron trifluoride to give difluoroboroxy Fischer carbene complexes 2, which undergo loss of the metal fragment at room temperature to form 1,2-diketones 3, 1,2-hydroxy ketones 4, or dimers 5 through a dimerization or decarbonylation-dimerization process of acyl radicals. Decomposition of 2 in the presence of electron-deficient alkenes 11 and 18 furnishes the two-, three-, and four-component coupling products 12, 13, 19, 20, and 21.
